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Trial record 14 of 157 for:    Diseases | ( Map: Costa Rica )

Safety and Efficacy Evaluation Of Pregabalin (Lyrica) With Patients With Generalized Anxiety Disorder

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ClinicalTrials.gov Identifier: NCT00624780
Recruitment Status : Completed
First Posted : February 27, 2008
Results First Posted : April 19, 2013
Last Update Posted : April 19, 2013
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Generalized Anxiety Disorder
Interventions Drug: Pregabalin
Drug: Lorazepam
Drug: Placebo
Enrollment 615
Recruitment Details  
Pre-assignment Details This study employed 3 treatments in Period 1 and 6 treatments in Period 2. Randomization occurred once, at the onset of Period 1.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Hide Arm/Group Description Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period Title: Treatment Optimization (Up to Week 12)
Started 154 52 154 52 153 50
Completed 121 39 112 38 114 39
Not Completed 33 13 42 14 39 11
Reason Not Completed
Adverse Event             7             5             15             3             9             5
Lack of Efficacy             5             2             10             5             9             1
Lost to Follow-up             1             0             2             0             2             1
Withdrawal by Subject             10             2             7             4             10             4
Other             10             4             8             2             9             0
Period Title: Fixed Dosing (Week 13 to Week 24)
Started 121 39 112 38 114 39
Completed 106 28 94 27 95 30
Not Completed 15 11 18 11 19 9
Reason Not Completed
Adverse Event             5             4             5             2             3             1
Lack of Efficacy             2             1             2             5             5             2
Lost to Follow-up             1             0             1             0             1             1
Withdrawal by Subject             2             3             6             3             6             2
Other             5             3             4             1             4             3
Period Title: Treatment Discontinuation (Week 25)
Started 106 28 94 27 95 30
Completed 104 28 91 26 95 29
Not Completed 2 0 3 1 0 1
Reason Not Completed
Adverse Event             1             0             2             1             0             1
Lack of Efficacy             1             0             0             0             0             0
Lost to Follow-up             0             0             1             0             0             0
Period Title: Follow-up (Week 26)
Started 104 28 91 26 95 29
Completed 102 27 89 26 93 29
Not Completed 2 1 2 0 2 0
Reason Not Completed
Death             0             0             1             0             0             0
Adverse Event             0             0             0             0             1             0
Lost to Follow-up             0             0             1             0             1             0
Withdrawal by Subject             1             0             0             0             0             0
Other             1             1             0             0             0             0
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo Total
Hide Arm/Group Description Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26). Total of all reporting groups
Overall Number of Baseline Participants 154 52 154 52 153 50 615
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 154 participants 52 participants 154 participants 52 participants 153 participants 50 participants 615 participants
18 to 44 years 75 30 100 28 86 27 346
45 to 64 years 79 22 51 24 66 23 265
Greater than or equal to 65 years 0 0 3 0 1 0 4
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 154 participants 52 participants 154 participants 52 participants 153 participants 50 participants 615 participants
Female
89
  57.8%
30
  57.7%
101
  65.6%
32
  61.5%
95
  62.1%
27
  54.0%
374
  60.8%
Male
65
  42.2%
22
  42.3%
53
  34.4%
20
  38.5%
58
  37.9%
23
  46.0%
241
  39.2%
1.Primary Outcome
Title Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Baseline, Week 1 post-treatment discontinuation (discontinuation occurred prior to Week 9)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included. n=participants evaluable at given time points for each group.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 15 19 21
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=15,19,21) 25.8  (4.23) 24.9  (4.15) 24.4  (4.88)
Change at Discontinuation Week 1 (n=15,19,18) -7.7  (6.75) -5.9  (7.20) -9.9  (10.81)
2.Primary Outcome
Title Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Baseline, Week 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. Here, 'N' (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 14 15 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
-12.0  (7.24) -5.9  (5.46) -9.7  (11.08)
3.Primary Outcome
Title Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Baseline, Week 1 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 58 52 52
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 25.0  (5.37) 24.7  (3.89) 24.6  (4.76)
Change at Discontinuation Week 1 -15.3  (7.76) -15.3  (6.71) -15.8  (7.92)
4.Primary Outcome
Title Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Baseline, Week 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 54 49 44
Mean (Standard Deviation)
Unit of Measure: units on a scale
-15.6  (7.42) -14.9  (7.11) -16.0  (7.96)
5.Primary Outcome
Title Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Baseline, Week 1 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included in Month 6 last visit analysis.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 109 30 94 29 100 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 25.5  (3.85) 24.2  (4.64) 24.7  (3.85) 24.9  (3.82) 24.6  (4.36) 24.9  (3.93)
Change at Discontinuation Week 1 -17.6  (7.25) -18.7  (5.36) -18.4  (6.33) -16.5  (7.25) -16.2  (8.11) -19.1  (6.69)
6.Primary Outcome
Title Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected.
Time Frame Baseline, Week 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
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Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included in Month 6 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 107 29 84 26 94 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
-16.6  (8.53) -19.1  (5.80) -18.3  (7.05) -16.0  (8.17) -16.7  (7.52) -18.7  (7.38)
7.Primary Outcome
Title Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1
Hide Description PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time Frame Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred prior to Week 9)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. ‘n’ = participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 15 18 20
Mean (Standard Deviation)
Unit of Measure: units on a scale
Last visit on treatment (n=15,18,20) 10.1  (8.72) 16.8  (13.20) 13.1  (10.75)
Change at Discontinuation Week 1 (n=15,18,18) 0.1  (9.89) -2.8  (7.99) -4.2  (6.12)
8.Primary Outcome
Title Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2
Hide Description PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time Frame Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants evaluable for this measure.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 14 15 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.0  (6.39) -2.7  (9.04) -3.2  (6.05)
9.Primary Outcome
Title Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1
Hide Description PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time Frame Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 58 52 50
Mean (Standard Deviation)
Unit of Measure: units on a scale
Last visit on treatment 7.2  (7.32) 6.5  (6.01) 5.0  (3.80)
Change at Discontinuation Week 1 1.9  (7.29) 1.4  (4.52) 2.3  (6.60)
10.Primary Outcome
Title Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2
Hide Description PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time Frame Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 54 49 44
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.1  (6.11) 2.0  (5.51) 1.6  (6.33)
11.Primary Outcome
Title Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1
Hide Description PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time Frame Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included in Month 6 last visit analysis. Here, 'N' (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 109 30 93 29 100 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
Last visit on treatment 5.2  (5.62) 4.9  (7.15) 3.9  (4.14) 6.5  (6.72) 5.3  (6.65) 4.7  (4.50)
Change at Discontinuation Week 1 1.7  (4.92) 0.0  (2.18) 1.1  (3.50) 1.0  (4.37) 3.0  (6.79) -0.1  (3.22)
12.Primary Outcome
Title Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2
Hide Description PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time Frame Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included in Month 6 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 106 29 84 26 93 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.8  (5.99) -1.0  (5.65) 1.7  (4.78) 1.8  (5.14) 2.2  (6.02) -0.1  (3.63)
13.Secondary Outcome
Title Number of Participants With Rebound Anxiety for Cohort 1 (Less Than 3-Month Last Visit)
Hide Description Rebound anxiety was defined as a rapid return of the participant’s original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value.
Time Frame 2 weeks post-treatment discontinuation (discontinuation occurred prior to Week 9)
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Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 15 19 18
Measure Type: Number
Unit of Measure: participants
1 5 1
14.Secondary Outcome
Title Number of Participants With Rebound Anxiety for Cohort 2 (3-Month Last Visit)
Hide Description Rebound anxiety was defined as a rapid return of the participant’s original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value.
Time Frame 2 weeks post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 58 52 48
Measure Type: Number
Unit of Measure: participants
3 1 2
15.Secondary Outcome
Title Number of Participants With Rebound Anxiety for Cohort 3 (6-Month Last Visit)
Hide Description Rebound anxiety was defined as a rapid return of the participant’s original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value.
Time Frame 2 weeks post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included in Month 6 last visit analysis. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 109 30 94 28 100 30
Measure Type: Number
Unit of Measure: participants
4 0 0 1 6 0
16.Secondary Outcome
Title Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 1 (Less Than 3-Month Last Visit)
Hide Description DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2.
Time Frame 2 weeks post-treatment discontinuation (discontinuation occurred prior to Week 9)
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Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 15 19 21
Measure Type: Number
Unit of Measure: participants
Newly developed DESS 6 0 3
Worsened DESS 0 0 0
17.Secondary Outcome
Title Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 2 (3-Month Last Visit)
Hide Description DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2.
Time Frame 2 weeks post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 1: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 58 52 52
Measure Type: Number
Unit of Measure: participants
Newly developed DESS 40 38 36
Worsened DESS 1 2 1
18.Secondary Outcome
Title Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit)
Hide Description DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2.
Time Frame 2 weeks post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included in Month 6 last visit analysis.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 109 30 94 29 100 30
Measure Type: Number
Unit of Measure: participants
Newly developed DESS 78 5 35 17 50 7
Worsened DESS 2 0 2 1 5 0
19.Secondary Outcome
Title Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2
Hide Description PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time Frame Baseline, Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. ‘n’ = participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 14 19 21
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=14,19,21) 13.6  (8.19) 17.6  (10.68) 16.4  (8.62)
Change at Discontinuation Week 1 (n=14,19,18) -3.4  (11.91) -3.3  (9.12) -5.9  (7.43)
Change at Discontinuation Week 2 (n=13,15,16) -4.7  (10.62) -2.7  (8.20) -5.4  (8.34)
20.Secondary Outcome
Title Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2
Hide Description PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time Frame Baseline, Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
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Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. ‘n’ = participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 57 51 52
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=57,51,52) 17.4  (7.81) 17.1  (9.84) 14.8  (7.86)
Change at Discontinuation Week 1 (n=57,51,49) -8.5  (9.40) -9.3  (9.48) -7.6  (9.53)
Change at Discontinuation Week 2 (n=53,48,44) -8.3  (9.53) -8.7  (9.68) -8.0  (9.70)
21.Secondary Outcome
Title Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2
Hide Description PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time Frame Baseline, Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included. N (Number of Participants Analyzed) = participants evaluable for this measure. ‘n’=participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 109 30 94 29 99 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=109,30,94,29,99,30) 17.8  (8.36) 17.8  (7.79) 16.1  (7.52) 17.4  (9.28) 16.8  (8.85) 14.9  (7.61)
Change at DC Week 1 (n=109,30,94,29,99,30) -11.0  (9.48) -12.9  (7.89) -11.0  (8.08) -9.9  (10.98) -8.7  (10.77) -10.4  (7.58)
Change at DC Week 2 (n=106,29,84,26,92,30) -9.8  (10.32) -13.8  (8.32) -10.8  (8.42) -10.2  (8.56) -9.6  (9.70) -10.3  (7.50)
22.Secondary Outcome
Title Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit)
Hide Description PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time Frame Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)
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Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. ‘n’ = participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 15 19 18
Mean (Standard Deviation)
Unit of Measure: units on a scale
Discontinuation Week 1 (n=15,19,18) 10.2  (7.97) 14.3  (10.04) 9.1  (9.25)
Discontinuation Week 2 (n=14,15,16) 8.2  (6.70) 14.1  (9.16) 10.6  (9.39)
23.Secondary Outcome
Title Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit)
Hide Description PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time Frame Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. ‘n’ = participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 58 52 49
Mean (Standard Deviation)
Unit of Measure: units on a scale
Discontinuation Week 1 (n=58,52,49) 9.1  (6.82) 8.0  (6.19) 7.3  (6.69)
Discontinuation Week 2 (n=54,49,44) 8.9  (7.28) 8.3  (6.32) 6.9  (6.38)
24.Secondary Outcome
Title Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit)
Hide Description PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Time Frame Week 1, 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included. N (Number of Participants Analyzed) = participants evaluable for this measure. ‘n’ = participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 109 30 94 29 99 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
Discontinuation Week 1 (n=109,30,94,29,99,30) 6.8  (6.56) 4.9  (5.73) 5.1  (4.45) 7.4  (6.43) 8.0  (7.45) 4.6  (4.22)
Discontinuation Week 2 (n=106,29,84,26,93,30) 7.9  (7.59) 4.1  (4.17) 5.7  (6.11) 7.1  (8.65) 7.1  (6.64) 4.6  (4.67)
25.Secondary Outcome
Title Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. ‘n’ = participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 15 18 20
Mean (Standard Deviation)
Unit of Measure: units on a scale
Last visit on treatment (n=15,18,20) 16.1  (8.46) 21.6  (6.18) 16.1  (10.11)
Change at Discontinuation Week 1 (n=15,18,18) 2.0  (11.45) -2.3  (4.63) -2.4  (3.31)
Change at Discontinuation Week 2 (n=14,15,16) -2.3  (9.47) -3.5  (5.34) -2.2  (4.18)
26.Secondary Outcome
Title Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected.
Time Frame Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. ‘n’ = participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 58 52 50
Mean (Standard Deviation)
Unit of Measure: units on a scale
Last visit on treatment (n=58,52,50) 8.0  (6.57) 8.5  (6.50) 6.7  (4.29)
Change at Discontinuation Week 1 (n=58,52,48) 1.7  (6.69) 0.9  (4.03) 2.3  (5.74)
Change at Discontinuation Week 2 (n=54,49,44) 1.5  (5.55) 1.5  (6.43) 1.5  (5.37)
27.Secondary Outcome
Title Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included. N(Number of Participants Analyzed) = participants evaluable for this measure. ‘n’ = participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 109 30 93 29 100 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
Last visit on treatment (n=109,30,93,29,100,30) 6.3  (5.89) 5.5  (6.12) 5.6  (5.02) 8.3  (6.49) 5.6  (6.17) 5.5  (4.66)
Change at DC Week 1 (n=109,30,93,28,99,30) 1.6  (4.37) -0.0  (2.30) 0.7  (3.08) 0.6  (2.69) 3.0  (5.73) 0.3  (3.01)
Change at DC Week 2 (n=107,29,84,26,94,30) 2.5  (5.74) -0.8  (5.33) 1.2  (3.90) 1.5  (5.08) 2.2  (5.39) 0.6  (3.76)
28.Secondary Outcome
Title Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit)
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)
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Per-protocol analysis set. Cohort 1: Participants who discontinued study prior to Week 9 and had at least 1 discontinuation assessment were included in less-than Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. ‘n’ = participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 15 19 18
Mean (Standard Deviation)
Unit of Measure: units on a scale
Discontinuation Week 1 (n=15,19,18) 18.1  (7.11) 19.0  (7.61) 14.1  (10.31)
Discontinuation Week 2 (n=14,15,16) 13.9  (7.33) 18.6  (6.15) 14.6  (10.41)
29.Secondary Outcome
Title Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit)
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected.
Time Frame Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)
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Per-protocol analysis set. Cohort 2: Participants who discontinued study from Week 9 to Week 15 and had at least 1 discontinuation assessment were included in Month 3 last visit analysis. N (Number of Participants Analyzed) = participants evaluable for this measure. ‘n’ = participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 58 52 48
Mean (Standard Deviation)
Unit of Measure: units on a scale
Discontinuation Week 1 (n=58,52,48) 9.6  (6.38) 9.4  (6.60) 8.8  (5.88)
Discontinuation Week 2 (n=54,49,44) 9.0  (6.44) 9.9  (7.04) 8.3  (6.48)
30.Secondary Outcome
Title Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit)
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24)
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Hide Analysis Population Description
Per-protocol analysis set. Cohort 3: Participants who discontinued study after Week 15 or completed Week 24 visit and had at least 1 discontinuation assessment were included. N (Number of Participants Analyzed) = participants evaluable for this measure. ‘n’ = participants evaluable at given time points for each group respectively.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 109 30 94 28 99 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
Discontinuation Week 1 (n=109,30,94,28,99,30) 7.9  (6.34) 5.5  (4.85) 6.3  (5.48) 8.4  (6.67) 8.4  (7.07) 7.07  (4.92)
Discontinuation Week 2 (n=107,29,84,26,94,30) 8.9  (7.60) 5.0  (4.32) 6.5  (6.36) 9.2  (8.28) 7.9  (6.27) 6.1  (6.00)
31.Secondary Outcome
Title Hamilton Anxiety Scale (HAM-A) Score for Period 1
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Baseline, Week 12
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Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. Last observation carried forward (LOCF) method was used to impute missing values.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
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Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 197 183 188
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 25.3  (4.39) 24.9  (3.87) 24.5  (4.39)
Week 12 8.0  (6.23) 8.9  (7.19) 7.9  (6.70)
32.Secondary Outcome
Title Hamilton Anxiety Scale (HAM-A) Score for Period 2
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 117 37 103 37 106 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 25.6  (3.82) 24.6  (4.66) 24.8  (3.77) 25.1  (3.92) 24.7  (4.41) 24.1  (4.03)
Week 24 7.0  (6.53) 7.1  (7.09) 6.5  (5.98) 10.2  (7.49) 5.7  (6.06) 6.6  (6.33)
33.Secondary Outcome
Title Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 12
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 194 180 185
Mean (Standard Deviation)
Unit of Measure: units on a scale
-17.4  (7.39) -16.0  (7.45) -16.7  (7.92)
34.Secondary Outcome
Title Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 24
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 117 37 103 37 106 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
-18.7  (7.33) -17.5  (6.89) -18.2  (6.59) -14.9  (7.85) -19.0  (7.24) -17.5  (8.34)
35.Secondary Outcome
Title Clinical Global Impression - Severity (CGI-S) Score for Period 1
Hide Description CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 197 183 188
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 4.6  (0.68) 4.5  (0.71) 4.4  (0.65)
Week 12 2.3  (1.06) 2.5  (1.17) 2.3  (1.00)
36.Secondary Outcome
Title Clinical Global Impression - Severity (CGI-S) Score for Period 2
Hide Description CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 117 37 103 37 106 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 4.7  (0.65) 4.5  (0.69) 4.5  (0.71) 4.5  (0.73) 4.4  (0.68) 4.5  (0.56)
Week 24 2.3  (1.08) 2.2  (1.16) 2.1  (0.97) 2.5  (1.24) 1.9  (0.90) 2.4  (0.98)
37.Secondary Outcome
Title Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 12
Hide Description CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. Here, 'N' (Number of Participants Analyzed) signifies those participants who were evaluable for this measure. LOCF method was used to impute missing values.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 195 181 186
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.3  (1.13) -2.1  (1.13) -2.1  (1.17)
38.Secondary Outcome
Title Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 24
Hide Description CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 117 37 103 37 106 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.4  (1.13) -2.3  (1.24) -2.4  (1.04) -2.0  (1.27) -2.5  (1.11) -2.2  (1.17)
39.Secondary Outcome
Title Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 1
Hide Description CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 197 183 188
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.9  (1.13) 1.9  (1.01) 1.9  (1.17)
40.Secondary Outcome
Title Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 2
Hide Description CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set: all randomized participants who had baseline with at least 1 discontinuation or efficacy visit, and were not major protocol violators. LOCF method was used to impute missing values.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 117 37 103 37 106 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.7  (0.99) 1.9  (1.15) 1.6  (0.75) 2.3  (1.53) 1.5  (0.91) 2.0  (1.07)
41.Other Pre-specified Outcome
Title Sheehan-Suicidality Tracking Scale (S-STS) Score
Hide Description Sheehan-Suicidality Tracking Scale (S-STS): an 8-item prospective rating scale that tracked treatment-emergent suicidal ideation and behaviors. Items 1a, 2-6, 7a, and 8 were scored on a 5-point Likert scale (ranging from 0= not at all to 4=extremely). Items 1, 1b, and 7 required yes or no responses. Total score ranged from 0 to 35, higher score indicated higher suicidal tendency.
Time Frame Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not statistically summarized but was available in individual participant listings and mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) due to change in planned analysis.
Arm/Group Title Pregabalin High Dose Pregabalin Low Dose Lorazepam
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12.
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
42.Other Pre-specified Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and Week 12, for period 1, and between Week 13 and Week 24, for period 2, that were absent before treatment or that worsened relative to pretreatment state.
Time Frame Baseline up to Week 12 (period 1), Week 13 up to Week 24 (period 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: all randomized participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for this measure during each specified period, for each group respectively.
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Hide Arm/Group Description:
Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6 fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26).
Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
Overall Number of Participants Analyzed 154 52 154 52 153 50
Measure Type: Number
Unit of Measure: participants
Period 1 (n=154,52,154,52,153,50) 103 37 100 40 95 35
Period 2 (n=121,39,112,38,114,39) 62 26 62 18 52 20
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Hide Arm/Group Description Period 1 (treatment optimization): Pregabalin capsule 150 milligram per day (mg/day) orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses in Week 1, pregabalin capsule 300 mg/day orally twice daily in 2 equally divided doses in Week 2 and pregabalin capsule 450 mg/day orally twice daily in 2 equally divided doses in Week 3 during 3-week upward titration. Flexible dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 450 mg/day or 600 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Continued pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Pregabalin capsule 150 mg/day orally twice daily in 2 equally divided doses during 3-week upward titration. Flexible dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of pregabalin capsule 150 mg/day or 300 mg/day orally twice daily in 2 equally divided doses up to Week 12. Period 2 (fixed dosing): Pregabalin was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Continued lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 24. Period 3 (treatment discontinuation): A 1-week blinded dose tapering period (Week 25). Participants were followed-up after 1 week (Week 26). Period 1 (treatment optimization): Lorazepam capsule 2 mg/day orally twice daily in 2 equally divided doses in Week 1, lorazepam capsule 3 mg/day orally in 2 divided doses (1 mg in morning, 2 mg at night) in Week 2 and 3, during 3-week upward titration. Flexible dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) depending on efficacy and tolerability up to Week 6. If participant had an adequate response at Week 6, fixed dosing of lorazepam capsule 3 or 4 mg/day orally twice daily in 2 divided doses (1 or 2 mg in morning, 2 mg at night) up to Week 12. Period 2 (fixed dosing): Lorazepam was discontinued with a blinded dose tapering over 1-week followed by matching placebo capsule orally twice daily up to Week 24. Period 3 (treatment discontinuation): Continued matching placebo capsule orally twice daily for 1 week (Week 25). Participants were followed-up after 1 week (Week 26).
All-Cause Mortality
Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/154 (1.30%)   0/52 (0.00%)   5/154 (3.25%)   2/52 (3.85%)   4/153 (2.61%)   0/50 (0.00%) 
Cardiac disorders             
Myocardial infarction * 1  0/154 (0.00%)  0/52 (0.00%)  0/154 (0.00%)  0/52 (0.00%)  1/153 (0.65%)  0/50 (0.00%) 
Myocardial ischaemia * 1  0/154 (0.00%)  0/52 (0.00%)  0/154 (0.00%)  0/52 (0.00%)  1/153 (0.65%)  0/50 (0.00%) 
Gastrointestinal disorders             
Abdominal hernia * 1  0/154 (0.00%)  0/52 (0.00%)  0/154 (0.00%)  1/52 (1.92%)  0/153 (0.00%)  0/50 (0.00%) 
Food poisoning * 1  0/154 (0.00%)  0/52 (0.00%)  0/154 (0.00%)  0/52 (0.00%)  1/153 (0.65%)  0/50 (0.00%) 
Inguinal hernia * 1  0/154 (0.00%)  0/52 (0.00%)  1/154 (0.65%)  0/52 (0.00%)  0/153 (0.00%)  0/50 (0.00%) 
Infections and infestations             
Infection * 1  0/154 (0.00%)  0/52 (0.00%)  1/154 (0.65%)  0/52 (0.00%)  0/153 (0.00%)  0/50 (0.00%) 
Typhoid fever * 1  0/154 (0.00%)  0/52 (0.00%)  0/154 (0.00%)  0/52 (0.00%)  1/153 (0.65%)  0/50 (0.00%) 
Injury, poisoning and procedural complications             
Subdural haematoma * 1  1/154 (0.65%)  0/52 (0.00%)  0/154 (0.00%)  0/52 (0.00%)  0/153 (0.00%)  0/50 (0.00%) 
Metabolism and nutrition disorders             
Diabetes mellitus inadequate control * 1  0/154 (0.00%)  0/52 (0.00%)  0/154 (0.00%)  1/52 (1.92%)  0/153 (0.00%)  0/50 (0.00%) 
Hyperglycaemia * 1  0/154 (0.00%)  0/52 (0.00%)  0/154 (0.00%)  1/52 (1.92%)  0/153 (0.00%)  0/50 (0.00%) 
Ketoacidosis * 1  0/154 (0.00%)  0/52 (0.00%)  0/154 (0.00%)  1/52 (1.92%)  0/153 (0.00%)  0/50 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Metastasis * 1  0/154 (0.00%)  0/52 (0.00%)  1/154 (0.65%)  0/52 (0.00%)  0/153 (0.00%)  0/50 (0.00%) 
Nervous system disorders             
Cerebral haemorrhage * 1  0/154 (0.00%)  0/52 (0.00%)  1/154 (0.65%)  0/52 (0.00%)  0/153 (0.00%)  0/50 (0.00%) 
Psychiatric disorders             
Anxiety * 1  1/154 (0.65%)  0/52 (0.00%)  0/154 (0.00%)  0/52 (0.00%)  0/153 (0.00%)  0/50 (0.00%) 
Depression * 1  0/154 (0.00%)  0/52 (0.00%)  1/154 (0.65%)  0/52 (0.00%)  0/153 (0.00%)  0/50 (0.00%) 
Generalised anxiety disorder * 1  0/154 (0.00%)  0/52 (0.00%)  1/154 (0.65%)  0/52 (0.00%)  1/153 (0.65%)  0/50 (0.00%) 
Suicidal ideation * 1  0/154 (0.00%)  0/52 (0.00%)  1/154 (0.65%)  0/52 (0.00%)  0/153 (0.00%)  0/50 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pregabalin High Dose, Pregabalin High Dose Pregabalin High Dose, Placebo Pregabalin Low Dose, Pregabalin Low Dose Pregabalin Low Dose, Placebo Lorazepam, Lorazepam Lorazepam, Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   110/154 (71.43%)   40/52 (76.92%)   108/154 (70.13%)   38/52 (73.08%)   100/153 (65.36%)   35/50 (70.00%) 
Ear and labyrinth disorders             
Vertigo * 1  4/154 (2.60%)  1/52 (1.92%)  5/154 (3.25%)  4/52 (7.69%)  3/153 (1.96%)  1/50 (2.00%) 
Gastrointestinal disorders             
Abdominal pain * 1  1/154 (0.65%)  1/52 (1.92%)  2/154 (1.30%)  3/52 (5.77%)  1/153 (0.65%)  0/50 (0.00%) 
Constipation * 1  10/154 (6.49%)  1/52 (1.92%)  4/154 (2.60%)  2/52 (3.85%)  2/153 (1.31%)  1/50 (2.00%) 
Diarrhoea * 1  10/154 (6.49%)  3/52 (5.77%)  8/154 (5.19%)  5/52 (9.62%)  9/153 (5.88%)  1/50 (2.00%) 
Dry mouth * 1  13/154 (8.44%)  3/52 (5.77%)  5/154 (3.25%)  2/52 (3.85%)  8/153 (5.23%)  4/50 (8.00%) 
Nausea * 1  17/154 (11.04%)  7/52 (13.46%)  12/154 (7.79%)  8/52 (15.38%)  18/153 (11.76%)  7/50 (14.00%) 
General disorders             
Fatigue * 1  16/154 (10.39%)  6/52 (11.54%)  15/154 (9.74%)  11/52 (21.15%)  15/153 (9.80%)  5/50 (10.00%) 
Irritability * 1  6/154 (3.90%)  1/52 (1.92%)  4/154 (2.60%)  2/52 (3.85%)  8/153 (5.23%)  1/50 (2.00%) 
Infections and infestations             
Influenza * 1  8/154 (5.19%)  3/52 (5.77%)  7/154 (4.55%)  0/52 (0.00%)  7/153 (4.58%)  0/50 (0.00%) 
Nasopharyngitis * 1  13/154 (8.44%)  2/52 (3.85%)  7/154 (4.55%)  5/52 (9.62%)  8/153 (5.23%)  4/50 (8.00%) 
Investigations             
Weight increased * 1  5/154 (3.25%)  1/52 (1.92%)  7/154 (4.55%)  3/52 (5.77%)  4/153 (2.61%)  0/50 (0.00%) 
Metabolism and nutrition disorders             
Decreased appetite * 1  6/154 (3.90%)  1/52 (1.92%)  3/154 (1.95%)  4/52 (7.69%)  6/153 (3.92%)  3/50 (6.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia * 1  4/154 (2.60%)  1/52 (1.92%)  3/154 (1.95%)  0/52 (0.00%)  3/153 (1.96%)  3/50 (6.00%) 
Back pain * 1  9/154 (5.84%)  1/52 (1.92%)  1/154 (0.65%)  0/52 (0.00%)  4/153 (2.61%)  2/50 (4.00%) 
Myalgia * 1  5/154 (3.25%)  4/52 (7.69%)  4/154 (2.60%)  2/52 (3.85%)  9/153 (5.88%)  1/50 (2.00%) 
Nervous system disorders             
Disturbance in attention * 1  12/154 (7.79%)  1/52 (1.92%)  3/154 (1.95%)  2/52 (3.85%)  6/153 (3.92%)  1/50 (2.00%) 
Dizziness * 1  37/154 (24.03%)  17/52 (32.69%)  28/154 (18.18%)  14/52 (26.92%)  20/153 (13.07%)  10/50 (20.00%) 
Headache * 1  38/154 (24.68%)  13/52 (25.00%)  36/154 (23.38%)  17/52 (32.69%)  33/153 (21.57%)  10/50 (20.00%) 
Paraesthesia * 1  6/154 (3.90%)  0/52 (0.00%)  3/154 (1.95%)  3/52 (5.77%)  5/153 (3.27%)  2/50 (4.00%) 
Sedation * 1  6/154 (3.90%)  2/52 (3.85%)  5/154 (3.25%)  0/52 (0.00%)  10/153 (6.54%)  1/50 (2.00%) 
Somnolence * 1  25/154 (16.23%)  7/52 (13.46%)  31/154 (20.13%)  9/52 (17.31%)  35/153 (22.88%)  13/50 (26.00%) 
Tremor * 1  5/154 (3.25%)  2/52 (3.85%)  1/154 (0.65%)  3/52 (5.77%)  6/153 (3.92%)  0/50 (0.00%) 
Psychiatric disorders             
Anxiety * 1  14/154 (9.09%)  6/52 (11.54%)  10/154 (6.49%)  1/52 (1.92%)  19/153 (12.42%)  5/50 (10.00%) 
Generalised anxiety disorder * 1  4/154 (2.60%)  2/52 (3.85%)  9/154 (5.84%)  2/52 (3.85%)  6/153 (3.92%)  2/50 (4.00%) 
Insomnia * 1  31/154 (20.13%)  15/52 (28.85%)  24/154 (15.58%)  12/52 (23.08%)  23/153 (15.03%)  13/50 (26.00%) 
Tension * 1  8/154 (5.19%)  1/52 (1.92%)  4/154 (2.60%)  0/52 (0.00%)  2/153 (1.31%)  1/50 (2.00%) 
Respiratory, thoracic and mediastinal disorders             
Cough * 1  1/154 (0.65%)  1/52 (1.92%)  2/154 (1.30%)  0/52 (0.00%)  2/153 (1.31%)  4/50 (8.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00624780     History of Changes
Other Study ID Numbers: A0081147
First Submitted: February 15, 2008
First Posted: February 27, 2008
Results First Submitted: March 5, 2013
Results First Posted: April 19, 2013
Last Update Posted: April 19, 2013