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Trial record 78 of 424 for:    Pregabalin

Efficacy and Safety of Pregabalin vs Placebo for Generalized Anxiety Disorder (GAD) Symptoms in Subjects Discontinuing Benzodiazepine Treatment and Remaining 6 Weeks on Study Medication, Free From Benzodiazepine Use. (GAD)

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ClinicalTrials.gov Identifier: NCT00368745
Recruitment Status : Completed
First Posted : August 25, 2006
Results First Posted : November 9, 2009
Last Update Posted : November 11, 2009
Sponsor:
Information provided by:
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Generalized Anxiety Disorder
Interventions Drug: Pregabalin
Drug: Placebo
Enrollment 108
Recruitment Details  
Pre-assignment Details Prior to randomization, subjects were stabilized on a therapeutic dose of open-label alprazolam (minimum of 2 weeks) if they entered the study on a stable alprazolam dose or for up to 4 weeks if entered on a different benzodiazepine. Alprazolam dose range during 2-4 week stabilization phase was 1-4 milligrams (mg) by mouth (PO) twice a day (BID).
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper. Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Period Title: Randomized to Double-blind Treatment
Started 57 51
Completed 56 [1] 50 [2]
Not Completed 1 1
[1]
One subject did not return following randomization; study drug not dispensed.
[2]
One subject did not want to participate in study.
Period Title: Double-blind Treatment Period
Started 56 50
Completed 30 19
Not Completed 26 31
Reason Not Completed
Adverse Event             6             6
Lack of Efficacy             7             16
Lost to Follow-up             1             0
Withdrawal by Subject             5             3
Other             7             6
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID Total
Hide Arm/Group Description Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper. Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper. Total of all reporting groups
Overall Number of Baseline Participants 56 50 106
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 56 participants 50 participants 106 participants
40.1  (10.6) 43.5  (11.3) 41.7  (11.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 56 participants 50 participants 106 participants
Female
42
  75.0%
34
  68.0%
76
  71.7%
Male
14
  25.0%
16
  32.0%
30
  28.3%
1.Primary Outcome
Title Number of Subjects at Endpoint (Post Alprazolam Free Week 6 or Last Observation Carried Forward [LOCF] Post Alprazolam Free Week 1) Who Are Benzodiazepine Free
Hide Description Number of subjects benzodiazepine free: < 2 doses rescue medication; negative urine benzodiazepine psychoactive toxicology assay (each visit Alprazolam Free phase); negative serum benzodiazepine alcohol assay (endpoint or LOCF).
Time Frame Endpoint (Post Alprazolam Free Week 6 or LOCF Post Alprazolam Free Week 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population: received at least 1 dose pregabalin or placebo. Primary outcome ITT = all treated subjects in alprazolam free phase. Endpoint = Post Alprazolam Free Week 6 or LOCF Post Alprazolam Free Week 1.
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 37 27
Measure Type: Number
Unit of Measure: participants
20 10
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Primary objective: evaluate the efficacy of pregabalin in maintaining the benzodiazepine free state in subjects with prior stable alprazolam use.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2838
Comments significance determined using 2-tailed significance level of 0.05
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel (CMH) with country as a covariate
2.Secondary Outcome
Title Mean Change From Baseline in Hamilton Anxiety Scale (HAM-A) Scores
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); lower score indicates less affected. Change from baseline: mean at observation minus mean at baseline.
Time Frame Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (Alprazolam Free [AF] Week 6)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT; subject has a baseline and at least 1 post-baseline measurement before week 13; endpoint = AF Week 6 or LOCF; (n) = number of subjects with data for analysis for pregabalin and placebo, respectively.
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 46 41
Least Squares Mean (Standard Error)
Unit of Measure: scores on scale
Alprazolam Taper (AT) Week 1 (n=46, 40) -0.82  (0.66) 0.67  (0.81)
AT Week 2 (n=45, 37) -1.72  (0.98) 2.17  (1.15)
AT Week 3 (n=33, 26) -2.59  (0.99) -0.21  (1.32)
AT Week 4 (n=18, 11) -1.47  (1.11) 1.91  (1.82)
AT Week 5 (n=8, 5) -2.36  (2.19) 2.86  (2.97)
AT Week 6 (n=17, 9) -1.26  (1.40) 2.41  (2.11)
Alprazolam Free (AF) Week 1 (n=39, 28) -0.43  (0.90) 2.40  (1.15)
AF Week 2 (n=35, 24) -2.15  (0.91) -1.14  (1.19)
AF Week 3 (n=31, 26) -3.46  (0.92) -2.47  (1.14)
AF Week 4 (n=31, 19) -3.58  (0.84) -3.58  (1.14)
AF Week 5 (n=27, 18) -3.85  (0.87) -3.34  (1.18)
AF Week 6 (n=22, 15) -5.62  (0.84) -4.77  (1.05)
Endpoint [LOCF] (n=46, 41) -2.01  (1.13) 2.77  (1.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Alprazolam Taper (AT) Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0709
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments Least squares (LS) Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.48
Confidence Interval 95%
-3.10 to 0.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.81
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.89
Confidence Interval 95%
-6.04 to -1.74
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.08
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0718
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.38
Confidence Interval 95%
-4.98 to 0.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.30
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0920
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.38
Confidence Interval 95%
-7.37 to 0.60
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.92
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT week 5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1371
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.22
Confidence Interval 95%
-12.67 to 2.23
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.04
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0882
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.68
Confidence Interval 95%
-7.96 to 0.61
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.04
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Alprazolam Free (AF) Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0135
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.83
Confidence Interval 95%
-5.05 to -0.61
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.11
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3924
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.01
Confidence Interval 95%
-3.38 to 1.35
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.18
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3868
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.00
Confidence Interval 95%
-3.29 to 1.30
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.14
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9966
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval 95%
-2.31 to 2.32
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.15
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6873
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.51
Confidence Interval 95%
-3.07 to 2.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.26
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5337
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.85
Confidence Interval 95%
-3.62 to 1.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.35
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Endpoint [LOCF]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.79
Confidence Interval 95%
-7.51 to -2.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.37
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Subjects With > = 6 Point Increase in Physician's Withdrawal Checklist (PWC) Scores
Hide Description PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Data not analyzed: PWC not measured at baseline.
Time Frame Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT; data not analyzed: PWC not measured at baseline.
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Number of Subjects With > = 5 New PWC Symptoms
Hide Description PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Data not analyzed: PWC not measured at baseline.
Time Frame Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT; data not analyzed: PWC not measured at baseline.
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Mean Change From Baseline in Physician's Withdrawal Checklist (PWC) Scores
Hide Description PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Change from baseline not analyzed as PWC was not measured at baseline. Mean PWS scores presented in Post-hoc outcome measure Mean PWS scores.
Time Frame Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT; Change from baseline not analyzed as PWC was not measured at baseline. Mean PWS scores presented in Post-hoc outcome measure Mean PWS scores.
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Mean Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Scores.
Hide Description CGI-S: 7-point scale to assess global change in subject condition compared to baseline; range 1 (no evidence of illness) to 7 (among the most severely ill); higher score = more affected. Change from baseline: mean at observation minus mean at baseline.
Time Frame Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )
Hide Outcome Measure Data
Hide Analysis Population Description
ITT; subject has a baseline and at least 1 post-baseline endpoint measurement; endpoint = AF Week 6 or LOCF; (n) = number of subjects with data for analysis for pregabalin and placebo, respectively.
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 45 41
Least Squares Mean (Standard Error)
Unit of Measure: scores on scale
Alprazolam Taper (AT) Week 1 (n=45, 40) -0.23  (0.13) 0.22  (0.15)
AT Week 2 (n=44, 37) -0.33  (0.17) 0.41  (0.19)
AT Week 3 (n=32, 27) -0.60  (0.20) -0.10  (0.26)
AT Week 4 (n=17, 11) -0.41  (0.21) -0.04  (0.32)
AT Week 5 (n=7, 5) -0.77  (0.27) -0.05  (0.40)
AT Week 6 (n=16, 9) -0.63  (0.32) 0.08  (0.43)
Alprazolam Free (AF) Week 1 (n=38, 28) -0.46  (0.17) 0.23  (0.21)
AF Week 2 (n=34, 24) -0.98  (0.20) -0.48  (0.26)
AF Week 3 (n=30, 26) -0.88  (0.22) -0.32  (0.27)
AF Week 4 (n=30, 19) -0.87  (0.18) -0.84  (0.25)
AF Week 5 (n=26, 18) -0.82  (0.19) -0.75  (0.26)
AF Week 6 (n=21, 15) -1.33  (0.20) -1.02  (0.25)
Endpoint [LOCF] (n=45, 41) -0.45  (0.21) 0.31  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Alprazolam Taper (AT) Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0052
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.45
Confidence Interval 95%
-0.76 to -0.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.16
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.74
Confidence Interval 95%
-1.11 to -0.38
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.18
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0528
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.50
Confidence Interval 95%
-1.00 to 0.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.25
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3085
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.37
Confidence Interval 95%
-1.11 to 0.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.35
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1807
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.72
Confidence Interval 95%
-1.92 to 0.47
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.47
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1074
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.71
Confidence Interval 95%
-1.58 to 0.17
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Alprazolam Free (AF) Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.69
Confidence Interval 95%
-1.10 to -0.28
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.20
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0503
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.50
Confidence Interval 95%
-0.99 to 0.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.25
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0364
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.56
Confidence Interval 95%
-1.09 to -0.04
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.26
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9140
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.03
Confidence Interval 95%
-0.51 to 0.46
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.24
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7789
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.08
Confidence Interval 95%
-0.62 to 0.47
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3189
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.32
Confidence Interval 95%
-0.95 to 0.32
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.31
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Endpoint [LOCF]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0031
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.76
Confidence Interval 95%
-1.26 to -0.27
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.25
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Mean Scores for Clinical Global Impression-Improvement (CGI-I) Scale
Hide Description CGI-I: 7-point scale to assess global change in subject condition compared to baseline; range 1 (very much improved) to 7 (very much worse); higher score = more affected.
Time Frame Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )
Hide Outcome Measure Data
Hide Analysis Population Description
ITT; subject has a baseline and endpoint measurement; endpoint = AF Week 6 or LOCF; (n) = number of subjects with data for analysis for pregabalin and placebo, respectively.
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 46 41
Least Squares Mean (Standard Error)
Unit of Measure: scores on scale
Alprazolam Taper (AT) Week 1 (n=46, 39) 3.52  (0.20) 3.90  (0.24)
AT Week 2 (n=45, 37) 3.17  (0.27) 3.98  (0.31)
AT Week 3 (n=33, 27) 2.88  (0.31) 3.47  (0.39)
AT Week 4 (n=18, 11) 3.09  (0.35) 3.01  (0.54)
AT Week 5 (n=8, 5) 2.63  (0.30) 3.44  (0.47)
AT Week 6 (n=17, 9) 3.00  (0.31) 3.86  (0.46)
Alprazolam Free (AF) Week 1 (n=39, 28) 2.93  (0.28) 3.90  (0.36)
AF Week 2 (n=35, 24) 2.39  (0.28) 3.27  (0.35)
AF Week 3 (n=30, 26) 2.15  (0.28) 2.93  (0.35)
AF Week 4 (n=31, 19) 2.20  (0.29) 2.46  (0.39)
AF Week 5 (n=27, 18) 2.29  (0.32) 2.77  (0.42)
AF Week 6 (n=22, 15) 1.52  (0.28) 2.18  (0.34)
Endpoint [LOCF] (n= 46, 41) 2.57  (0.30) 3.52  (0.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Alprazolam Taper (AT) Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1260
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.37
Confidence Interval 95%
-0.86 to 0.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.24
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0074
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.81
Confidence Interval 95%
-1.40 to -0.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1250
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.59
Confidence Interval 95%
-1.35 to 0.17
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.38
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8991
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.08
Confidence Interval 95%
-1.17 to 1.32
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.60
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1747
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.81
Confidence Interval 95%
-2.07 to 0.46
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.53
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0744
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.85
Confidence Interval 95%
-1.79 to 0.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.45
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Alprazolam Free (AF) Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0063
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.98
Confidence Interval 95%
-1.67 to -0.29
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.35
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0140
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.87
Confidence Interval 95%
-1.56 to -0.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.34
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0267
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.78
Confidence Interval 95%
-1.46 to -0.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.34
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5104
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.26
Confidence Interval 95%
-1.03 to 0.52
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.38
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2702
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.48
Confidence Interval 95%
-1.35 to 0.39
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.43
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1241
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.66
Confidence Interval 95%
-1.52 to 0.19
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Endpoint [LOCF]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0109
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.95
Confidence Interval 95%
-1.67 to -0.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.36
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Mean Scores for Patient Global Impression-Improvement (PGI-I)
Hide Description PGI-I: subject rated 7-point scale measures change in overall status; range 1 (very much improved) to 7 (very much worse).
Time Frame Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )
Hide Outcome Measure Data
Hide Analysis Population Description
ITT; endpoint = AF Week 6 or LOCF; (n) = number of subjects with data for analysis for pregabalin and placebo, respectively.
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 46 41
Least Squares Mean (Standard Error)
Unit of Measure: scores on scale
Alprazolam Taper (AT) Week 1 (n=46, 40) 3.16  (0.23) 3.82  (0.27)
AT Week 2 (n= 45, 37) 3.13  (0.32) 4.03  (0.36)
AT Week 3 (n=33, 26) 2.93  (0.28) 3.31  (0.35)
AT Week 4 (n=18, 11) 3.12  (0.34) 2.98  (0.52)
AT Week 5 (n=8, 5) 2.91  (0.37) 3.75  (0.58)
AT Week 6 (n=17, 9) 2.93  (0.42) 3.38  (0.63)
Alprazolam Free (AF) Week 1 (n=39, 28) 2.95  (0.26) 3.45  (0.33)
AF Week 2 (n=35, 24) 2.34  (0.27) 2.94  (0.34)
AF Week 3 (n=31, 26) 2.28  (0.28) 2.92  (0.35)
AF Week 4 (n=30, 19) 2.43  (0.29) 2.73  (0.38)
AF Week 5 (n=27, 18) 2.32  (0.31) 2.70  (0.41)
AF Week 6 (n=22, 14) 1.53  (0.27) 2.48  (0.35)
Endpoint [LOCF] (n=46, 41) 2.71  (0.32) 3.74  (0.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Alprazolam Taper (AT) Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0226
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.66
Confidence Interval 95%
-1.22 to -0.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0099
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.90
Confidence Interval 95%
-1.58 to -0.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.34
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2827
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.38
Confidence Interval 95%
-1.07 to 0.32
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.35
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8232
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.13
Confidence Interval 95%
-1.07 to 1.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.58
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2409
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.85
Confidence Interval 95%
-2.41 to 0.72
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.66
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4760
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.45
Confidence Interval 95%
-1.73 to 0.84
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.61
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Alprazolam Free (AF) Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1252
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.50
Confidence Interval 95%
-1.14 to 0.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.32
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0717
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.60
Confidence Interval 95%
-1.26 to 0.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.33
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0707
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.64
Confidence Interval 95%
-1.33 to 0.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.35
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4341
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.30
Confidence Interval 95%
-1.08 to 0.47
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3700
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.38
Confidence Interval 95%
-1.23 to 0.47
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0328
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.96
Confidence Interval 95%
-1.83 to -0.08
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.43
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Endpoint [LOCF]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0096
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.03
Confidence Interval 95%
-1.80 to -0.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.39
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Mean Change From Baseline in Digit Symbol Substitution Test (DSST) Scores
Hide Description DSST: subject-rated; evaluates aspects of cognition (includes attending to directions, processing speed, sustained attention, visual-motor integration, learning and psychomotor speed). Subject matches symbol (1 to 9) with corresponding number key (1 to 9); number of correct symbol-number pairs completed by subject over a 90-second test period determines DSST score. Change: mean at observation minus mean at baseline. Data summarized as change from baseline to endpoint.
Time Frame Baseline, Endpoint (AF Week 6 )
Hide Outcome Measure Data
Hide Analysis Population Description
ITT; subject has baseline and endpoint (final visit) measurement; endpoint = AF Week 6 or LOCF.
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 33 29
Least Squares Mean (Standard Error)
Unit of Measure: scores on scale
13.10  (2.64) 13.47  (2.95)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8897
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country and baseline as the covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.37
Confidence Interval 95%
-5.74 to 4.99
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.68
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Time to Discontinuation
Hide Description The 25th percentile estimate of time until discontinuation is based on Kaplan-Meier estimates. Event day is the study day when the subject discontinued from study.
Time Frame Baseline, Week 13 (Final Visit/Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT; Week 13 (Final Visit/Early Termination) or LOCF.
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 19 24
Measure Type: Number
Unit of Measure: days
51 33
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0626
Comments p-value is from the log-rank statistic from the tests for equality over treatment as strata and country used as covariate
Method Log Rank
Comments [Not Specified]
11.Secondary Outcome
Title Time to First Use of Rescue Medication
Hide Description The 25th percentile estimate of time until first use of rescue medication is based on Kaplan-Meier estimates. Event day is the study day when the subject first used rescue medication. Rescue medication: packet with 2 doses alprazolam to take only in the event subject experiences severe symptoms of benzodiazepine withdrawal or rebound anxiety.
Time Frame Baseline, Week 13 (Final Visit/Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT; Week 13 (Final Visit/Early Termination) or LOCF
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 11 17
Measure Type: Number
Unit of Measure: days
63 30
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0148
Comments p-value is from the log-rank statistic from the tests for equality over treatment as strata and country used as covariate
Method Log Rank
Comments [Not Specified]
12.Secondary Outcome
Title Number of Subjects in Relapse Free State at 6-week Benzodiazepine-free Endpoint (Alprazolam Free Week 6)
Hide Description Number of subjects benzodiazepine free: < 2 doses rescue medication; negative urine toxicology assay (each visit Alprazolam Free phase), negative urine alcohol assay (Alprazolam Free Week 6 = endpoint or LOCF). Relapse: > = 2 intakes rescue medication, positive urine and /or alcohol assays, unable to tolerate alprazolam taper, or discontinuation.
Time Frame Alprazolam Free Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT; endpoint = AF Week 6 or LOCF.
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 22 15
Measure Type: Number
Unit of Measure: participants
21 12
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1159
Comments p-value is obtained using Cochran-Mantel-Haenszel option
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
13.Post-Hoc Outcome
Title Mean Scores Physician's Withdrawal Checklist (PWC)
Hide Description Mean scores at each visit for PWC: 20-item physician-rated interview measures presence of anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception, and cognition); range 0 (not present) to 3 (severe). Total score: 0 to 60; higher score = more affected. Mean scores entered as post-hoc analysis as Mean change from baseline in PWS scores not analyzed: PWS not measured at baseline.
Time Frame Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6 )
Hide Outcome Measure Data
Hide Analysis Population Description
ITT; (n) = number of subjects with data for analysis for pregabalin and placebo, respectively. Endpoint = AF Week 6 or LOCF. Refer to measure Mean Change From Baseline in Physician's Withdrawal Checklist (PWC) Scores.
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description:
Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.
Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Overall Number of Participants Analyzed 46 41
Least Squares Mean (Standard Error)
Unit of Measure: scores on scale
Alprazolam Taper (AT) Week 1 (n=43, 40) 6.32  (1.40) 8.50  (1.45)
AT Week 2 (n=44,37) 6.37  (1.18) 10.00  (1.34)
AT Week 3 (n=33, 26) 6.56  (1.40) 9.41  (1.76)
AT Week 4 (n=18, 11) 5.63  (0.89) 9.04  (1.37)
AT Week 5 (n=7, 5) 7.30  (1.52) 9.58  (2.32)
AT Week 6 (n=17, 9) 6.82  (1.39) 12.55  (2.07)
Alprazolam Free (AF) Week 1 (n=39, 28) 6.78  (1.15) 10.70  (1.45)
AF Week 2 (n=33, 24) 4.71  (0.93) 6.43  (1.19)
AF Week 3 (n=30, 26) 6.86  (0.85) 7.16  (1.05)
AF Week 4 (n=30, 19) 7.43  (0.89) 6.99  (1.17)
AF Week 5 (n=27, 18) 7.87  (0.76) 8.25  (1.00)
AF Week 6 (n=22, 15) 2.40  (0.94) 5.51  (1.16)
Endpoint [LOCF] (n=46, 41) 6.48  (1.23) 10.28  (1.44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Alprazolam Taper (AT) Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1220
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.18
Confidence Interval 95%
-4.97 to 0.60
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.40
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0053
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.63
Confidence Interval 95%
-6.15 to -1.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.26
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1048
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.85
Confidence Interval 95%
-6.32 to 0.62
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.73
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0357
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.41
Confidence Interval 95%
-6.57 to -0.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.52
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4263
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.28
Confidence Interval 95%
-8.82 to 4.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.67
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AT Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0104
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.73
Confidence Interval 95%
-9.96 to -1.51
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.02
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Alprazolam Free (AF) Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0069
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.92
Confidence Interval 95%
-6.73 to -1.12
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.40
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2185
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.71
Confidence Interval 95%
-4.47 to 1.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.37
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7832
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.29
Confidence Interval 95%
-2.41 to 1.83
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.06
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7062
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.44
Confidence Interval 95%
-1.90 to 2.79
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.16
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7161
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.38
Confidence Interval 95%
-2.49 to 1.73
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.04
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments AF Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0376
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.11
Confidence Interval 95%
-6.03 to -0.19
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.43
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
Comments Endpoint [LOCF]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0122
Comments contrasts performed using Dunnett's Test
Method ANCOVA
Comments LS Means from the ANCOVA model with treatment as the main effect and country as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.80
Confidence Interval 95%
-6.74 to -0.85
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.48
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Hide Arm/Group Description Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper. Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
All-Cause Mortality
Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Affected / at Risk (%) Affected / at Risk (%)
Total   0/56 (0.00%)   0/50 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pregabalin 75 mg to 300 mg PO BID Placebo 75 mg to 300 mg PO BID
Affected / at Risk (%) Affected / at Risk (%)
Total   33/56 (58.93%)   29/50 (58.00%) 
Ear and labyrinth disorders     
Hyperacusis  1  3/56 (5.36%)  1/50 (2.00%) 
Eye disorders     
Vision blurred   5/56 (8.93%)  2/50 (4.00%) 
Gastrointestinal disorders     
Diarrhoea   3/56 (5.36%)  5/50 (10.00%) 
Nausea   5/56 (8.93%)  7/50 (14.00%) 
Vomiting   3/56 (5.36%)  0/50 (0.00%) 
General disorders     
Asthenia   3/56 (5.36%)  5/50 (10.00%) 
Fatigue   2/56 (3.57%)  3/50 (6.00%) 
Irritability   0/56 (0.00%)  4/50 (8.00%) 
Oedema peripheral   5/56 (8.93%)  0/50 (0.00%) 
Musculoskeletal and connective tissue disorders     
Pain in extremity   3/56 (5.36%)  0/50 (0.00%) 
Nervous system disorders     
Dizziness   12/56 (21.43%)  3/50 (6.00%) 
Headache   7/56 (12.50%)  13/50 (26.00%) 
Paraesthesia *  6/56 (10.71%)  0/50 (0.00%) 
Somnolence   3/56 (5.36%)  2/50 (4.00%) 
Tremor   2/56 (3.57%)  4/50 (8.00%) 
Psychiatric disorders     
Anxiety   11/56 (19.64%)  10/50 (20.00%) 
Insomnia   4/56 (7.14%)  7/50 (14.00%) 
Skin and subcutaneous tissue disorders     
Hyperhidrosis   3/56 (5.36%)  0/50 (0.00%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v11.1
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 < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 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: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00368745     History of Changes
Other Study ID Numbers: A0081092
First Submitted: August 23, 2006
First Posted: August 25, 2006
Results First Submitted: August 10, 2009
Results First Posted: November 9, 2009
Last Update Posted: November 11, 2009