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A Study of Duloxetine in Elderly Generalized Anxiety Disorder

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ClinicalTrials.gov Identifier: NCT01118780
Recruitment Status : Completed
First Posted : May 7, 2010
Results First Posted : September 2, 2013
Last Update Posted : September 2, 2013
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Generalized Anxiety Disorder
Interventions Drug: Duloxetine
Drug: Placebo
Enrollment 291
Recruitment Details  
Pre-assignment Details Study had 3 periods: a screening period (3 to 30 days prior to randomization, no study drug administered), a treatment period (10 weeks), and a taper period (2 weeks). Participants who completed the treatment period were considered to have completed the study. Participant Flow and results, unless specified otherwise, are during treatment period.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Period Title: Overall Study
Started 151 140
Completed 115 105
Not Completed 36 35
Reason Not Completed
Adverse Event             15             15
Death             1             0
Lack of Efficacy             2             6
Physician Decision             2             0
Protocol Violation             3             6
Withdrawal by Subject             13             8
Arm/Group Title Duloxetine Placebo Total
Hide Arm/Group Description

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other). Total of all reporting groups
Overall Number of Baseline Participants 151 140 291
Hide Baseline Analysis Population Description
All randomized participants.
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 151 participants 140 participants 291 participants
71.43  (5.39) 71.70  (5.04) 71.56  (5.22)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 151 participants 140 participants 291 participants
Female
114
  75.5%
112
  80.0%
226
  77.7%
Male
37
  24.5%
28
  20.0%
65
  22.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 151 participants 140 participants 291 participants
Hispanic or Latino
55
  36.4%
47
  33.6%
102
  35.1%
Not Hispanic or Latino
96
  63.6%
93
  66.4%
189
  64.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 151 participants 140 participants 291 participants
American Indian or Alaska Native
17
  11.3%
18
  12.9%
35
  12.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
   3.3%
0
   0.0%
5
   1.7%
White
129
  85.4%
120
  85.7%
249
  85.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
2
   1.4%
2
   0.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 151 participants 140 participants 291 participants
Argentina 17 12 29
Austria 13 10 23
Canada 10 8 18
Germany 20 20 40
Mexico 21 21 42
Poland 27 29 56
Puerto Rico 7 5 12
Spain 9 9 18
United Kingdom 10 7 17
United States 17 19 36
Hamilton Anxiety Rating Scale (HAMA) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 151 participants 140 participants 291 participants
24.62  (6.40) 24.36  (7.11) 24.49  (6.74)
[1]
Measure Description: The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA Total Score consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.
Years Since Onset of Generalized Anxiety Disorder (GAD)   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 151 participants 140 participants 291 participants
12.78  (16.40) 11.83  (14.55) 12.32  (15.52)
[1]
Measure Description: GAD was defined as excessive anxiety and worry, present more days than not, for at least 6 months, in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revised (DSM-IV TR). The excessive anxiety and worry must have been difficult to control and must have caused significant distress or impairment in normal functioning.
1.Primary Outcome
Title Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) Total Score
Hide Description The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and at least 1 post-baseline HAMA Total Score.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 143 131
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-15.86  (0.63) -11.69  (0.67)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 4.17
Confidence Interval (2-Sided) 95%
2.47 to 5.88
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.86
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
2.Secondary Outcome
Title Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Global Functional Impairment Score
Hide Description The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Functional Impairment Score (SDS Global Score) was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated a higher functional impairment in the participant's work/social/family life. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and at least 1 post-baseline SDS Global Functional Impairment Score.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 140 131
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-8.60  (0.60) -5.37  (0.64)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 3.23
Confidence Interval (2-Sided) 95%
1.61 to 4.85
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.82
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
3.Secondary Outcome
Title Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item)
Hide Description The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Psychic Anxiety Factor Score was the sum of Items 1 to 6 and Item 14 and could have ranged from 0 to 28. The HAMA Somatic Anxiety Factor Score was the sum of Items 7 to 13 and could have ranged from 0 to 28. The HAMA Anxious Mood Item Score was the score for Item 1 and the HAMA Tension Item Score was the score for Item 2. In each case, higher scores indicated a greater degree of symptom severity. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and at least 1 post-baseline HAMA factor or item score.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 143 131
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
HAMA Psychic Anxiety Factor Score (n=143, 131) -8.59  (0.36) -6.19  (0.38)
HAMA Somatic Anxiety Factor Score (n=143, 131) -7.33  (0.33) -5.57  (0.35)
HAMA Anxious Mood Item Score (n=142, 131) -1.77  (0.08) -1.24  (0.09)
HAMA Tension Item Score (n=143, 131) -1.48  (0.08) -1.17  (0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for the change from baseline to Week 10 in the HAMA Psychic Anxiety Factor Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.40
Confidence Interval (2-Sided) 95%
1.43 to 3.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.49
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for the change from baseline to Week 10 in the HAMA Somatic Anxiety Factor Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.76
Confidence Interval (2-Sided) 95%
0.87 to 2.65
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.45
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for the change from baseline to Week 10 in the HAMA Anxious Mood Item Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.30 to 0.74
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments The p-value is for the change from baseline to Week 10 in the HAMA Tension Item Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.09 to 0.53
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
4.Secondary Outcome
Title Change From Baseline to Week 10 Endpoint in Hospital Anxiety Depression Scale (HADS) Subscale Scores
Hide Description HADS was a 14-item questionnaire with 2 subscales (anxiety and depression). Each item was rated on a 4-point scale (0 to 3) and higher scores indicated a greater dysfunction. The HADS Anxiety Subscale Score was the sum of the odd numbered items and scores could have ranged from 0 to 21. The HADS Depression Subscale Score was the sum of the even numbered items and scores could have ranged from 0 to 21. Higher scores indicated a greater dysfunction. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and at least 1 post-baseline HADS Subscale Score.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 143 132
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
HADS Anxiety Subscale -7.81  (0.37) -5.62  (0.39)
HADS Depression Subscale -3.29  (0.29) -1.61  (0.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for the change from baseline to Week 10 in the HADS Anxiety Subscale Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.19
Confidence Interval (2-Sided) 95%
1.20 to 3.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.50
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for the change from baseline to Week 10 in the HADS Depression Subscale Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.69
Confidence Interval (2-Sided) 95%
0.89 to 2.49
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.41
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
5.Secondary Outcome
Title Clinical Global Impressions of Improvement Scale (CGI-Improvement) at Week 10
Hide Description CGI-Improvement measured the clinician's perception of the participant's improvement at the time of assessment compared with the start of treatment. Scores could have ranged from 1 (very much improved) to 7 (very much worse). Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit.
Time Frame Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with at least 1 post-baseline CGI-Improvement Score.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 143 132
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
2.10  (0.10) 2.63  (0.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.26 to 0.79
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.14
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
6.Secondary Outcome
Title Patient's Global Impressions of Improvement Scale (PGI-Improvement) at Week 10
Hide Description PGI-Improvement measured the participant's perception of his or her improvement at the time of assessment compared with the start of treatment. Scores could have ranged from 1 (very much better) to 7 (very much worse). Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit.
Time Frame Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with at least 1 post-baseline PGI-Improvement Score.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 143 132
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
2.35  (0.11) 2.97  (0.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.33 to 0.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.15
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
7.Secondary Outcome
Title Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales
Hide Description The BPI-SF Pain Severity Subscale was a participant-rated questionnaire that measured the severity of pain. Severity scores could have ranged from 0 (no pain) to 10 (pain as bad as you can imagine) for questions assessing worst pain, least pain, and average pain in the past 24 hours, and pain right now. The BPI-SF Interference Subscale measured the interference of pain with the participant's ability to function. Interference scores could have ranged from 0 (does not interfere) to 10 (completely interferes) for questions assessing interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Least squares (LS) means were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and at least 1 post-baseline BPI-SF Pain Severity or Interference Subscale Score.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 141 132
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Worst Pain (n=141, 132) -1.44  (0.21) -0.90  (0.22)
Least Pain (n=141, 132) -0.92  (0.17) -0.50  (0.19)
Average Pain (n=141, 132) -1.10  (0.18) -0.68  (0.19)
Pain Right Now (n=141, 132) -0.81  (0.18) -0.59  (0.20)
General Activity (n=140, 131) -1.45  (0.23) -0.92  (0.24)
Mood (n=140, 131) -1.59  (0.22) -1.19  (0.23)
Walking Ability (n=140, 131) -0.91  (0.23) -0.31  (0.24)
Normal Work (n=139, 131) -1.21  (0.23) -0.83  (0.24)
Relations With Other People (n=140, 131) -0.96  (0.21) -0.80  (0.22)
Sleep (n=140, 131) -1.58  (0.27) -1.07  (0.28)
Enjoyment of Life (n=140, 131) -1.74  (0.23) -1.24  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.059
Comments The p-value is for the change from baseline to Week 10 in BPI-SF Worst Pain Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
-0.02 to 1.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.079
Comments The p-value is for the change from baseline to Week 10 in BPI-SF Least Pain Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
-0.05 to 0.89
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.24
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.089
Comments The p-value is for the change from baseline to Week 10 in BPI-SF Average Pain Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
-0.06 to 0.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.25
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.371
Comments The p-value is for the change from baseline to Week 10 in BPI-SF Pain Right Now Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
-0.27 to 0.73
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.25
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.066
Comments The p-value is for the change from baseline to Week 10 in BPI-SF General Activity Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
-0.04 to 1.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.140
Comments The p-value is for the change from baseline to Week 10 in BPI-SF Mood Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
-0.13 to 0.95
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments The p-value is for the change from baseline to Week 10 in BPI-SF Walking Ability Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.03 to 1.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.187
Comments The p-value is for the change from baseline to Week 10 in BPI-SF Normal Work Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
-0.19 to 0.94
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.515
Comments The p-value is for the change from baseline to Week 10 in BPI-SF Relations With Other People Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.34 to 0.68
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.26
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.141
Comments The p-value is for the change from baseline to Week 10 in BPI-SF Sleep Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
-0.17 to 1.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.34
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.088
Comments The p-value is for the change from baseline to Week 10 in BPI-SF Enjoyment of Life Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
-0.07 to 1.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
8.Secondary Outcome
Title Change From Baseline to Week 10 in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Total Score
Hide Description The Q-LES-Q-SF was a participant-rated questionnaire designed to assess the degree of enjoyment and satisfaction experienced during the past week. The questionnaire consisted of 16 items rated on a 5-point scale ranging from 1 (very poor) to 5 (very good). The total raw score was the sum of Items 1 to 14 and could have ranged from 14 to 70. Total raw scores were converted to, and expressed as, the percentage of the maximum possible score. Percent=100*(total raw score – 14)/56. Higher scores indicated higher levels of enjoyment/satisfaction. Least squares (LS) mean were calculated and analyzed using analysis of covariance (ANCOVA) adjusted for treatment, pooled investigator, age category, and baseline.
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and at least 1 post-baseline Q-LES-Q-SF Total Score; Last observation carried forward (LOCF).
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 134 125
Least Squares Mean (Standard Error)
Unit of Measure: percent of maximum possible score
15.11  (1.45) 9.35  (1.52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -5.76
Confidence Interval (2-Sided) 95%
-9.4 to -2.1
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.87
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Negative values indicated improvement over placebo.
9.Secondary Outcome
Title Number of Participants With Treatment-Emergent Suicide-Related Ideation and Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS)
Hide Description The C-SSRS captured the occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Suicidal behavior: a "yes" answer to any 1 of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Treatment-emergent was the worsening or new occurrence of suicidal behavior or ideation during treatment compared with baseline (Week 0).
Time Frame Baseline through 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and at least 1 post-baseline C-SSRS Score.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 144 133
Measure Type: Number
Unit of Measure: participants
Treatment-Emergent Suicidal Ideation 3 5
Treatment-Emergent Suicidal Behavior 0 0
10.Secondary Outcome
Title Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Work/School, Social Life, and Family/Home Management Individual Impairment Scores
Hide Description The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). Higher values indicated a higher functional impairment in the participant's work/social/family life. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and at least 1 post-baseline SDS Work/School, Social Life/Leisure Activities, or Family/Home Management Individual Impairment Scores.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 140 131
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Work/School (n=56, 51) -2.21  (0.33) -1.08  (0.40)
Social Life/Leisure Activities (n=140, 131) -2.84  (0.22) -1.94  (0.23)
Family/Home Management (n=140, 131) -2.82  (0.22) -1.61  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments The p-value is for the change from baseline to Week 10 in SDS for Work/School Impairment Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.27 to 1.98
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.43
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments The p-value is for the change from baseline to Week 10 in SDS for Social Life/Leisure Activities Impairment Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.32 to 1.48
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for the change from baseline to Week 10 in SDS for Family/Home Management Impairment Score.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
0.61 to 1.81
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.30
Estimation Comments LS mean difference was calculated by placebo minus duloxetine. Positive values indicated improvement over placebo.
11.Secondary Outcome
Title Percentage of Participants With Response or Remission at Week 10 (Response and Remission Rates)
Hide Description Response was a ≥50% improvement (reduction) in the Hamilton Anxiety Rating Scale (HAMA) Total Score at treatment period endpoint compared with baseline. Two definitions were used to determine remission: Definition 1 (HAMA Total Score ≤7 at endpoint) and Definition 2 (HAMA Total Score ≤10 at endpoint). The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and 1 post-baseline HAMA Total Score; Last observation carried forward (LOCF).
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 143 132
Measure Type: Number
Unit of Measure: percentage of participants
Response 71.3 45.5
Remission (HAMA Total Score ≤7) 44.8 29.5
Remission (HAMA Total Score ≤10) 62.2 40.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for percentage of participants having HAMA response at Week 10 and was adjusted for pooled investigator.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for percentage of participants having remission (HAMA Total Score ≤7) at Week 10 and was adjusted for pooled investigator.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for percentage of participants having remission (HAMA Total Score ≤10) at Week 10 and was adjusted for pooled investigator.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants With Functional Remission at Week 10 (Functional Remission Rate)
Hide Description Two definitions, using the Sheehan Disability Scale (SDS) Global Functional Impairment Score (SDS Global Score), were used to determine functional remission: Definition 1 (SDS Global Score ≤5 at endpoint) and Definition 2 (SDS Global Score ≤6 at endpoint). The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Score was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated a higher functional impairment in the participant's work/social/family life.
Time Frame Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with at least 1 post-baseline SDS Global Score; Last observation carried forward (LOCF).
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 151 140
Measure Type: Number
Unit of Measure: percentage of participants
Functional Remission (SDS Global Score ≤5) 55.0 32.9
Functional Remission (SDS Global Score ≤6) 60.9 40.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for the percentage of participants having functional remission (SDS Global Score ≤5) at Week 10 and was adjusted for pooled investigator.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for the percentage of participants having functional remission (SDS Global Score ≤6) at Week 10 and was adjusted for pooled investigator.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
13.Secondary Outcome
Title Percentage of Participants With Sustained Improvement (Sustained Improvement Rate)
Hide Description Two definitions, using the Hamilton Anxiety Rating Scale (HAMA) Total Score at endpoint compared with baseline, were used to determine sustained improvement: Definition 1 [sustained improvement overall required a ≥30% improvement (reduction) in the HAMA Total Score at treatment period endpoint, at an earlier visit prior to endpoint, and at all visits in between] and Definition 2 (sustained improvement from Week 2 required a ≥30% reduction at treatment period endpoint, at Week 2, and at all visits in between). Both definitions required at least 2 post-baseline visits. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.
Time Frame (Baseline through 10 weeks) and (Baseline, Week 2 through Week 10)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who had baseline and the required number of post-baseline HAMA Total Scores.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 134 124
Measure Type: Number
Unit of Measure: percentage of participants
Sustained Improvement Overall (n=134, 124) 74.6 55.6
Sustained Improvement From Week 2 (n=134, 123) 26.9 17.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments The p-value is for the percentage of participants having HAMA sustained improvement overall and was adjusted for pooled investigator.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments The p-value is for the percentage of participants having HAMA sustained improvement from Week 2 and was adjusted for pooled investigator.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
14.Secondary Outcome
Title Adverse Events (AEs) Leading to Discontinuation From Study
Hide Description The number of participants who discontinued from the study due to an AE (serious or other AE) during the treatment period. A summary of serious and other AEs is located in the Reported Adverse Events module.
Time Frame Baseline through 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 151 140
Measure Type: Number
Unit of Measure: participants
16 15
15.Secondary Outcome
Title Percentage of Participants Reporting Falling Down
Hide Description The percentage of participants who reported 1 or more falls at or before Week 10.
Time Frame Baseline through 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with no falls recorded at Baseline and at least 1 post-baseline assessment for falls.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 113 114
Measure Type: Number
Unit of Measure: percentage of participants
6.2 3.5
16.Secondary Outcome
Title Time to First Response
Hide Description The time (days) to first response, defined as a ≥50% improvement (reduction) from baseline in the Hamilton Anxiety Rating Scale (HAMA) Total Score. Participants who did not have a response were censored at the last treatment period visit. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.
Time Frame Baseline through 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. The number of censored participants (n)=36 participants in the duloxetine treatment arm and n=60 participants in the placebo treatment arm.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 151 140
Median (95% Confidence Interval)
Unit of Measure: days
50.00
(48.00 to 51.00)
70.00
(50.00 to 72.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments The p-value was adjusted for pooled investigator.
Method Log Rank
Comments [Not Specified]
17.Secondary Outcome
Title Time to First Remission
Hide Description The time (days) to first remission. Two definitions, using the Hamilton Anxiety Rating Scale (HAMA) Total Score, were used to determine remission: Definition 1 (HAMA Total Score ≤7 at endpoint) and Definition 2 (HAMA Total Score ≤10 at endpoint). Participants who did not have remission were censored at the last treatment period visit. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.
Time Frame Baseline through 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (pts). The number of censored pts (n)=72 pts in the duloxetine treatment arm and n=92 pts in the placebo treatment arm for time to first remission (HAMA Total Score ≤7) and n=49 pts in the duloxetine treatment arm and n=71 pts in the placebo treatment arm for the time to first remission (HAMA Total Score ≤10).
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 151 140
Median (95% Confidence Interval)
Unit of Measure: days
Remission (HAMA Total Score ≤7)
71.00
(69.00 to 72.00)
NA [1] 
(72.00 to NA)
Remission (HAMA Total Score ≤10)
51.00
(50.00 to 57.00)
71.00
(70.00 to 75.00)
[1]
The median and upper confidence interval was not calculable because an insufficient number of participants reached the event (HAMA Total Score ≤7).
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for the time to first remission (HAMA Total Score ≤10) and was adjusted for pooled investigator.
Method Log Rank
Comments [Not Specified]
18.Secondary Outcome
Title Time to Sustained Improvement Overall
Hide Description Time (days) to the earliest visit at which the Hamilton Anxiety Rating Scale (HAMA) Total Score was a ≥30% improvement (reduction) from baseline that was sustained through the last treatment period visit. Participants who did not meet sustained improvement criteria were censored at the last treatment period visit. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.
Time Frame Baseline through 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. The number of participants censored (n)=43 participants in the duloxetine treatment arm and n=63 participants in the placebo treatment arm.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 151 140
Median (95% Confidence Interval)
Unit of Measure: days
30.00
(29.00 to 48.00)
50.00 [1] 
(30.00 to NA)
[1]
The upper 95% confidence interval was not calculable due to an insufficient number of participants reaching the event by 10 weeks.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments The p-value was adjusted for pooled investigator.
Method Log Rank
Comments [Not Specified]
19.Secondary Outcome
Title Time to First Functional Remission
Hide Description Time (days) to first functional remission. Two definitions, using the Sheehan Disability Scale (SDS) Global Functional Impairment Score (SDS Global Score), were used to determine functional remission: Definition 1 (SDS Global Score ≤5 at endpoint) and Definition 2 (SDS Global Score ≤6 at endpoint). Participants, who did not have an SDS Global Score ≤5 or ≤6, were censored at the last treatment period visit. The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Score was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated a higher functional impairment in the participant's work/social/family life.
Time Frame Baseline through 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants (pts). Number of pts censored (n)=50 pts in duloxetine treatment arm and n=73 pts in placebo treatment arm for time to first functional remission (SDS Global Score ≤5) and n=37 pts in duloxetine treatment arm and n=60 pts in placebo treatment arm time to first functional remission (SDS Global Score ≤6).
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 151 140
Median (95% Confidence Interval)
Unit of Measure: days
Functional Remission (SDS Global Score ≤5)
50.00
(48.00 to 68.00)
72.00 [1] 
(71.00 to NA)
Functional Remission (SDS Global Score ≤6)
31.00
(29.00 to 49.00)
71.00
(50.00 to 73.00)
[1]
The upper 95% confidence interval was not calculable because an insufficient number of participants had functional remission (SDS Global Score ≤5) by endpoint.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments The p-value is for the time to first functional remission (SDS Global Functional Impairment Score ≤5) and was adjusted for pooled investigator.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments The p-value is for time to first functional remission (SDS Global Functional Impairment Score ≤6) and was adjusted for pooled investigator.
Method Log Rank
Comments [Not Specified]
20.Secondary Outcome
Title Time to First Improvement
Hide Description The time (days) to first improvement, defined as a Clinical Global Impression of Improvement (CGI-Improvement) Score ≤2. Participants who did not have a CGI-I Score ≤2 were censored at the last treatment period visit. CGI-Improvement measured the clinician's perception of the participant's improvement at the time of assessment compared with the start of treatment. Scores could have ranged from 1 (very much improved) to 7 (very much worse). A CGI-Improvement Score of ≤2 was much improved or very much improved.
Time Frame Baseline through 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. The number of participants censored (n)=37 participants in the duloxetine treatment arm and n=58 participants in the placebo treatment arm.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
Overall Number of Participants Analyzed 151 140
Median (95% Confidence Interval)
Unit of Measure: days
31.00
(29.00 to 50.00)
52.00
(49.00 to 71.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value was adjusted for pooled investigator.
Method Log Rank
Comments [Not Specified]
21.Other Pre-specified Outcome
Title Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period
Hide Description Treatment-emergent AEs were newly occurring AEs or a worsening of AEs during the taper period. A summary of serious AEs and other AEs during the treatment period (baseline through 10 weeks) is located in the Reported Adverse Events module.
Time Frame 2 weeks during the taper period
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who entered the taper period.
Arm/Group Title Duloxetine 30 mg Then Placebo Duloxetine 60 mg Then 30 mg Placebo
Hide Arm/Group Description:
Participants, whose final dose during the treatment period was duloxetine 60 mg, were administered a 30-mg duloxetine capsule orally, once daily for 1 week followed by a placebo capsule orally, once daily for 1 week, during the 2-week taper period.
Participants, whose final dose during the treatment period was 90 mg or 120 mg duloxetine, were administered duloxetine 60 mg (two 30-mg duloxetine capsules) orally, once daily for 1 week followed by a 30-mg duloxetine capsule orally, once daily for 1 week, during the 2-week taper period.
Participants, whose final dose during the treatment period was either placebo or duloxetine 30 mg, were administered a placebo capsule orally, once daily for 2 weeks, during the 2-week taper period.
Overall Number of Participants Analyzed 31 34 114
Measure Type: Number
Unit of Measure: participants
Any Serious AE 0 0 0
Non-Serious AE, Dizziness 1 1 1
Non-Serious AE, Fatigue 0 1 2
Non-Serious AE, Hyperhidrosis 0 0 2
Non-Serious AE, Nausea 0 1 1
Non-Serious AE, Tinnitus 2 0 0
Non-Serious AE, Constipation 0 0 1
Non-Serious AE, Cystitis 0 0 1
Non-Serious AE, Headache 0 0 1
Non-Serious AE, Musculoskeletal Chest Pain 0 1 0
Non-Serious AE, Nightmare 0 1 0
Non-Serious AE, Oropharyngeal Pain 0 1 0
Non-Serious AE, Pain 0 0 1
Non-Serious AE, Vertigo 1 0 0
Time Frame Baseline through 10 weeks.
Adverse Event Reporting Description Serious adverse events and other adverse events during the treatment period. Refer to the Other Pre-Specified Outcome Measure 21 for a summary of serious adverse events and other adverse events during the taper period.
 
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description

30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).

Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks.

A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other).
All-Cause Mortality
Duloxetine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Duloxetine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/151 (1.99%)      0/140 (0.00%)    
Cardiac disorders     
Angina pectoris  1  1/151 (0.66%)  1 0/140 (0.00%)  0
Gastrointestinal disorders     
Large intestinal obstruction  1 [1]  1/151 (0.66%)  1 0/140 (0.00%)  0
Vascular disorders     
Hypertensive crisis  1  1/151 (0.66%)  1 0/140 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
[1]
Event resulted in death
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Duloxetine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   89/151 (58.94%)      71/140 (50.71%)    
Ear and labyrinth disorders     
Vertigo  1  5/151 (3.31%)  5 1/140 (0.71%)  1
Gastrointestinal disorders     
Abdominal pain upper  1  6/151 (3.97%)  6 4/140 (2.86%)  4
Constipation  1  14/151 (9.27%)  14 5/140 (3.57%)  5
Diarrhoea  1  7/151 (4.64%)  8 5/140 (3.57%)  5
Dry mouth  1  11/151 (7.28%)  11 2/140 (1.43%)  2
Nausea  1  17/151 (11.26%)  18 9/140 (6.43%)  9
Infections and infestations     
Nasopharyngitis  1  3/151 (1.99%)  3 10/140 (7.14%)  10
Injury, poisoning and procedural complications     
Fall  1  6/151 (3.97%)  9 2/140 (1.43%)  2
Metabolism and nutrition disorders     
Decreased appetite  1  6/151 (3.97%)  6 1/140 (0.71%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  1/151 (0.66%)  1 6/140 (4.29%)  6
Nervous system disorders     
Dizziness  1  12/151 (7.95%)  13 10/140 (7.14%)  11
Headache  1  16/151 (10.60%)  18 9/140 (6.43%)  10
Somnolence  1  9/151 (5.96%)  9 3/140 (2.14%)  3
Psychiatric disorders     
Insomnia  1  2/151 (1.32%)  2 7/140 (5.00%)  7
Skin and subcutaneous tissue disorders     
Hyperhidrosis  1  5/151 (3.31%)  5 0/140 (0.00%)  0
Pruritus  1  6/151 (3.97%)  6 2/140 (1.43%)  2
Indicates events were collected by 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.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01118780     History of Changes
Other Study ID Numbers: 12866
F1J-MC-HMGF ( Other Identifier: Eli Lilly and Company )
First Submitted: May 5, 2010
First Posted: May 7, 2010
Results First Submitted: June 25, 2013
Results First Posted: September 2, 2013
Last Update Posted: September 2, 2013