Generalized Anxiety Disorder
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of pregabalin as compared to placebo in the treatment of patients with general anxiety disorder (GAD). Efficacy will be measured by the improvement in the total Hamilton Anxiety Rating Scale (HAM-A) scores from baseline observed following 8 weeks of double-blind treatment or at earlier termination during the double-blind treatment phase and analyzed using a mixed linear model for repeated measures.
Detailed description
Further enrollment in this study was stopped on January 28, 2008 based on the recommendation of an independent data monitoring committee. The recommendation to stop the study was not based on any safety findings.
Interventions
DRUGpregabalin
pregabalin 150-600 mg/day flexibly dosed for the first 6 weeks and fixed dosed for the last 2 weeks of total 8 weeks of double blind study period, + concurrent GAD treatment from the open-label study period
DRUGplacebo
placebo + concurrent GAD treatment from the open-label study period
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult male and female subjects with primary DSM-IV diagnosis of GAD, as confirmed by the MINI structured interview. * Historical failure to respond optimally to a GAD treatment
Exclusion criteria
* Current primary DSM-IV (Diagnostic and Statistical Manual of Mental Disorders 4th edition) diagnosis of major depressive disorder with or without seasonal pattern, dysthmic disorder, depressive disorder NOS (not otherwise specified), social phobia, panic disorder with or without agoraphobia, post traumatic stress disorder, dissociative disorder, borderline personality disorder, obsessive-compulsive disorder, antisocial personality disorder, as defined in the DSM-IV TR (Diagnostic and Statistical Manual of Mental Disorders 4th edition, Text Revision). * Past and/or current DSM-IV diagnosis of schizophrenia, schizoaffective disorder, other psychotic disorders, bipolar disorders (I or II), factitious disorder or cognitive disorder (including delirium, dementia, and amnestic disorder).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Anxiety Rating Scale (HAM-A) Total Scores | Baseline, 8 weeks | Change from baseline: average across visit weeks using mixed model. HAM-A=clinician-rated interview measuring presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges from 0 to 56; higher score indicates greater anxiety. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Weeks 1 through Week 8 | Responders = YES if subjects achieved a \>= 50% decrease in HAM-A total score from Baseline to respective study week. HAM-A is a clinician-rated interview measuring the presence of anxiety-related symptoms in 14 areas. Total score ranges from 0 to 56; higher score indicates greater anxiety. |
| Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 1 through Week 8 | Participant in remission defined as HAM-A total score of \<= 7. HAM-A=clinician-rated interview measuring presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges 0 - 56; higher score indicates greater anxiety. |
| Time to Onset of Sustained Hamilton Anxiety Rating Scale (HAM-A) Improvement | Week 8 | Time to sustained improvement was defined as time to 50% or greater reduction in HAM-A total score from Baseline, which was sustained for the remainder of the study. HAM-A is a clinician-rated interview measuring the presence of anxiety-related symptoms in 14 areas. Total score ranges from 0 to 56; a higher score indicates greater anxiety. |
| Change in HAM-A Total Score at Weekly Visits | Baseline, Weeks 1 through Week 8 | Change: score at each study week minus score at baseline. HAM-A, a clinician-rated interview, measures presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges from 0 to 56; higher score indicates greater anxiety. |
| Clinical Global Impression of Severity (CGI-S) Score | Week 8 | CGI-S is a clinician-rated instrument measuring the severity of a subject's symptoms on a 7-point categorical scale. Scores range from 1 (not at all ill) to 7 (among the most extremely ill patients). Higher score indicates that the subject is more ill. |
| Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Weeks 1 through Week 8 | Change: score at each study week minus score at baseline. HAM-D, clinician-rated interview, measures presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, & weight loss). Total score ranges from 0 to 52; higher scores indicate more depression. |
| Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 1 through Week 8 | Responders = YES using CGI-I if score indicated much improved or very much improved at the last study week. CGI-I is a clinician-rated instrument that measures change in subject's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). |
Countries
Czechia, Estonia, Finland, Hungary, Russia, Serbia, Ukraine, United States
Participant flow
Recruitment details
The study was conducted in 55 centers in 8 countries (United States, Russian Federation, Czech Republic, Ukraine, Serbia, Hungary, Finland, and Estonia).
Pre-assignment details
After a screening phase (Period 1), subjects entered an 8-week open-label treatment optimzation phase (Period 2). Only those subjects who partially responded to background Generalized Anxiety Disorder (GAD) treatment (escitalopram, paroxetine, or venlafaxine XR) and met all inclusion/exclusion criteria were eligible for randomization (Period 3).
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin Pregabalin doses of 150 milligrams (mg)/day, 300 mg/day, 450 mg/day, and 600 mg/day was administered orally, twice daily (BID), with or without food, during the double-blind phase. Flexible dosing of pregabalin was allowed during the first 6 weeks; fixed dosing was required for the last 2 weeks of this period.Subjects were required to remain on a stable dose of their concurrent Generalized Anxiety Disorder (GAD) treatment (ie, escitalopram, paroxetine, or venlafaxine XR). | 180 |
| Placebo Placebo was administrated orally, twice daily (BID) with or without food, during the double-blind phase. Subjects were required to remain on a stable dose of their concurrent GAD treatment (ie, escitalopram, paroxetine, or venlafaxine XR). | 176 |
| Total | 356 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 4 |
| Overall Study | Due to termination of the study | 54 | 52 |
| Overall Study | Laboratory abnormality | 0 | 2 |
| Overall Study | Lack of Efficacy | 0 | 3 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 2 |
Baseline characteristics
| Characteristic | Total | Pregabalin | Placebo |
|---|---|---|---|
| Age, Continuous | 43.6 years STANDARD_DEVIATION 12 | 43.7 years STANDARD_DEVIATION 11.5 | 43.5 years STANDARD_DEVIATION 12.5 |
| Sex: Female, Male Female | 244 Participants | 129 Participants | 115 Participants |
| Sex: Female, Male Male | 112 Participants | 51 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 81 / — | 59 / — |
| serious Total, serious adverse events | 1 / — | 3 / — |
Outcome results
Primary
Change in Hamilton Anxiety Rating Scale (HAM-A) Total Scores
Change from baseline: average across visit weeks using mixed model. HAM-A=clinician-rated interview measuring presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges from 0 to 56; higher score indicates greater anxiety.
Time frame: Baseline, 8 weeks
Population: Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment. All efficacy analyses included the ITT subjects who had a Baseline and a post-Baseline assessment of the respective efficacy endpoints.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change in Hamilton Anxiety Rating Scale (HAM-A) Total Scores | -7.6 score on scale | Standard Error 0.35 |
| Placebo | Change in Hamilton Anxiety Rating Scale (HAM-A) Total Scores | -6.4 score on scale | Standard Error 0.36 |
Comparison: Null hypothesis: no difference between Pregabalin (150-600 mg/day) BID and Placebo BID treatment groups. An initial sample size of 173 subjects per double-blind treatment group was calculated to provide at least 90% power to detect an effect size (ie, difference in the true means between 2 treatment groups/standard deviation) of 0.36 for the HAM-A total score change from Baseline using a 2-sided nominal significance level of 4.9%.95% CI: [-2.16, -0.26]Mixed Models Analysis
Secondary
Change in HAM-A Total Score at Weekly Visits
Change: score at each study week minus score at baseline. HAM-A, a clinician-rated interview, measures presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges from 0 to 56; higher score indicates greater anxiety.
Time frame: Baseline, Weeks 1 through Week 8
Population: Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment. All efficacy analyses included the ITT subjects who had a Baseline and a post-Baseline assessment of the respective efficacy endpoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change in HAM-A Total Score at Weekly Visits | Week 3 (n=157;n=160) | -7.0 score on scale | Standard Error 0.45 |
| Pregabalin | Change in HAM-A Total Score at Weekly Visits | Week 5 (n=135;n=130) | -8.4 score on scale | Standard Error 0.49 |
| Pregabalin | Change in HAM-A Total Score at Weekly Visits | Week 2 (n=166;n=163) | -6.3 score on scale | Standard Error 0.43 |
| Pregabalin | Change in HAM-A Total Score at Weekly Visits | Week 6 (n=122;n=125) | -9.2 score on scale | Standard Error 0.49 |
| Pregabalin | Change in HAM-A Total Score at Weekly Visits | Week 4 (n=153;n=150) | -8.3 score on scale | Standard Error 0.46 |
| Pregabalin | Change in HAM-A Total Score at Weekly Visits | Week 8 (n=126;n=127) | -9.3 score on scale | Standard Error 0.56 |
| Pregabalin | Change in HAM-A Total Score at Weekly Visits | Week 1 (n=164;n=169) | -4.4 score on scale | Standard Error 0.37 |
| Placebo | Change in HAM-A Total Score at Weekly Visits | Week 8 (n=126;n=127) | -8.0 score on scale | Standard Error 0.56 |
| Placebo | Change in HAM-A Total Score at Weekly Visits | Week 1 (n=164;n=169) | -3.1 score on scale | Standard Error 0.37 |
| Placebo | Change in HAM-A Total Score at Weekly Visits | Week 2 (n=166;n=163) | -5.2 score on scale | Standard Error 0.43 |
| Placebo | Change in HAM-A Total Score at Weekly Visits | Week 3 (n=157;n=160) | -5.5 score on scale | Standard Error 0.45 |
| Placebo | Change in HAM-A Total Score at Weekly Visits | Week 4 (n=153;n=150) | -7.0 score on scale | Standard Error 0.47 |
| Placebo | Change in HAM-A Total Score at Weekly Visits | Week 5 (n=135;n=130) | -7.6 score on scale | Standard Error 0.49 |
| Placebo | Change in HAM-A Total Score at Weekly Visits | Week 6 (n=122;n=125) | -8.0 score on scale | Standard Error 0.49 |
Comparison: Week 195% CI: [-2.3, -0.4]Mixed Models Analysis
Comparison: Week 295% CI: [-2.2, 0.1]Mixed Models Analysis
Comparison: Week 395% CI: [-2.7, -0.2]Mixed Models Analysis
Comparison: Week 495% CI: [-2.6, -0.1]Mixed Models Analysis
Comparison: Week 595% CI: [-2.1, 0.5]Mixed Models Analysis
Comparison: Week 695% CI: [-2.5, 0.1]Mixed Models Analysis
Comparison: Week 895% CI: [-2.9, 0.2]Mixed Models Analysis
Secondary
Change in Hamilton Depression Rating Scale (HAM-D) Total Score
Change: score at each study week minus score at baseline. HAM-D, clinician-rated interview, measures presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, & weight loss). Total score ranges from 0 to 52; higher scores indicate more depression.
Time frame: Weeks 1 through Week 8
Population: Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment, and had a baseline and post-baseline efficacy assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 3 n=156,160 | -3.5 score on scale | Standard Error 0.32 |
| Pregabalin | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 5 n=135, 130 | -4.3 score on scale | Standard Error 0.33 |
| Pregabalin | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 2 n=165,164 | -3.1 score on scale | Standard Error 0.3 |
| Pregabalin | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 6 n=122, 125 | -4.7 score on scale | Standard Error 0.33 |
| Pregabalin | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 4 n=153, 149 | -4.7 score on scale | Standard Error 0.29 |
| Pregabalin | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 8 n= 126, 127 | -4.8 score on scale | Standard Error 0.4 |
| Pregabalin | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 1 n=165,168 | -2.1 score on scale | Standard Error 0.28 |
| Placebo | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 8 n= 126, 127 | -3.8 score on scale | Standard Error 0.4 |
| Placebo | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 1 n=165,168 | -1.3 score on scale | Standard Error 0.28 |
| Placebo | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 2 n=165,164 | -2.4 score on scale | Standard Error 0.31 |
| Placebo | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 3 n=156,160 | -2.8 score on scale | Standard Error 0.32 |
| Placebo | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 4 n=153, 149 | -3.3 score on scale | Standard Error 0.29 |
| Placebo | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 5 n=135, 130 | -3.9 score on scale | Standard Error 0.34 |
| Placebo | Change in Hamilton Depression Rating Scale (HAM-D) Total Score | Week 6 n=122, 125 | -3.8 score on scale | Standard Error 0.33 |
Comparison: Week 195% CI: [-1.5, 0]ANCOVA
Comparison: Week 295% CI: [-1.5, 0.2]ANCOVA
Comparison: Week 395% CI: [-1.6, 0.1]ANCOVA
Comparison: Week 495% CI: [-2.1, -0.6]ANCOVA
Comparison: Week 595% CI: [-1.3, 0.5]ANCOVA
Comparison: Week 695% CI: [-1.8, 0]ANCOVA
Comparison: Week 895% CI: [-2.1, 0.1]ANCOVA
Secondary
Clinical Global Impression of Severity (CGI-S) Score
CGI-S is a clinician-rated instrument measuring the severity of a subject's symptoms on a 7-point categorical scale. Scores range from 1 (not at all ill) to 7 (among the most extremely ill patients). Higher score indicates that the subject is more ill.
Time frame: Week 8
Population: Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment, and had a baseline and post-baseline efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Clinical Global Impression of Severity (CGI-S) Score | Normal, not ill at all | 28 participants |
| Pregabalin | Clinical Global Impression of Severity (CGI-S) Score | Borderline, mentally ill | 49 participants |
| Pregabalin | Clinical Global Impression of Severity (CGI-S) Score | Mildly ill | 49 participants |
| Pregabalin | Clinical Global Impression of Severity (CGI-S) Score | Moderately ill | 46 participants |
| Pregabalin | Clinical Global Impression of Severity (CGI-S) Score | Markedly ill | 2 participants |
| Pregabalin | Clinical Global Impression of Severity (CGI-S) Score | Severely ill | 2 participants |
| Pregabalin | Clinical Global Impression of Severity (CGI-S) Score | Among the most extremely ill | 0 participants |
| Pregabalin | Clinical Global Impression of Severity (CGI-S) Score | Not assessed | 0 participants |
| Placebo | Clinical Global Impression of Severity (CGI-S) Score | Not assessed | 1 participants |
| Placebo | Clinical Global Impression of Severity (CGI-S) Score | Normal, not ill at all | 18 participants |
| Placebo | Clinical Global Impression of Severity (CGI-S) Score | Markedly ill | 8 participants |
| Placebo | Clinical Global Impression of Severity (CGI-S) Score | Borderline, mentally ill | 37 participants |
| Placebo | Clinical Global Impression of Severity (CGI-S) Score | Among the most extremely ill | 0 participants |
| Placebo | Clinical Global Impression of Severity (CGI-S) Score | Mildly ill | 63 participants |
| Placebo | Clinical Global Impression of Severity (CGI-S) Score | Severely ill | 1 participants |
| Placebo | Clinical Global Impression of Severity (CGI-S) Score | Moderately ill | 48 participants |
Comparison: Week 8 Last Observation Carried Forward (LOCF)95% CI: [1.07, 2.3]Cumulative Logit Model
Secondary
Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score
Responders = YES using CGI-I if score indicated much improved or very much improved at the last study week. CGI-I is a clinician-rated instrument that measures change in subject's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).
Time frame: Week 1 through Week 8
Population: Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment, and had a baseline and post-baseline efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 1: Yes | 62 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 5: Yes | 89 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 3: Yes | 93 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 5: No | 45 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 2: Yes | 94 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 6: Yes | 83 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 3: No | 62 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 6: No | 38 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 1: No | 101 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 8: Yes | 80 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 8 (LOCF): No | 61 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 4: Yes | 97 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 2: No | 72 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 8: No | 43 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 4: No | 55 participants |
| Pregabalin | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 8 (LOCF): Yes | 113 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 4: No | 61 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 1: Yes | 49 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 1: No | 120 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 2: Yes | 74 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 2: No | 89 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 3: Yes | 76 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 3: No | 86 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 4: Yes | 88 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 8 (LOCF): Yes | 110 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 5: Yes | 81 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 5: No | 50 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 6: Yes | 76 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 6: No | 49 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 8 (LOCF): No | 66 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 8: Yes | 82 participants |
| Placebo | Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score | Week 8: No | 45 participants |
Comparison: Week 195% CI: [0.96, 2.47]Regression, Logistic
Comparison: Week 295% CI: [1.01, 2.47]Regression, Logistic
Comparison: Week 395% CI: [1.09, 2.82]Regression, Logistic
Comparison: Week 495% CI: [0.77, 2.05]Regression, Logistic
Comparison: Week 595% CI: [0.72, 2.11]Regression, Logistic
Comparison: Week 695% CI: [0.84, 2.5]Regression, Logistic
Comparison: Week 895% CI: [0.61, 1.84]Regression, Logistic
Comparison: Week 8 (LOCF) Last Observation Carried Forward95% CI: [0.71, 1.76]Regression, Logistic
Secondary
Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A)
Responders = YES if subjects achieved a \>= 50% decrease in HAM-A total score from Baseline to respective study week. HAM-A is a clinician-rated interview measuring the presence of anxiety-related symptoms in 14 areas. Total score ranges from 0 to 56; higher score indicates greater anxiety.
Time frame: Weeks 1 through Week 8
Population: Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment, and had a baseline and post-baseline efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 1 Responder: Yes | 21 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 1 Responder: No | 143 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 2 Responder: Yes | 39 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 2 Responder: No | 127 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 3 Responder: Yes | 51 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 3 Responder: No | 106 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 4 Responder: Yes | 64 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 4 Responder: No | 89 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 5 Responder: Yes | 58 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 5 Responder: No | 77 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 6 Responder: Yes | 57 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 6 Responder: No | 65 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 8 Responder: Yes | 63 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 8 Responder: No | 63 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 8 (LOCF) Responder: Yes | 84 participants |
| Pregabalin | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 8 (LOCF) Responder: No | 93 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 8 (LOCF) Responder: No | 114 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 1 Responder: Yes | 8 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 5 Responder: Yes | 46 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 1 Responder: No | 161 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 8 Responder: Yes | 47 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 2 Responder: Yes | 26 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 5 Responder: No | 84 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 2 Responder: No | 137 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 8 (LOCF) Responder: Yes | 62 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 3 Responder: Yes | 23 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 6 Responder: Yes | 48 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 3 Responder: No | 137 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 8 Responder: No | 80 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 4 Responder: Yes | 46 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 6 Responder: No | 77 participants |
| Placebo | Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A) | Week 4 Responder: No | 104 participants |
Comparison: Week 195% CI: [1.37, 8.24]Regression, Logistic
Comparison: Week 295% CI: [0.9, 2.87]Regression, Logistic
Comparison: Week 395% CI: [1.76, 5.66]Regression, Logistic
Comparison: Week 495% CI: [1.06, 3.05]Regression, Logistic
Comparison: Week 595% CI: [0.9, 2.73]Regression, Logistic
Comparison: Week 695% CI: [0.86, 2.66]Regression, Logistic
Comparison: Week 895% CI: [1.08, 3.22]Regression, Logistic
Comparison: Week 8 (last observation carried forward, LOCF)95% CI: [1.12, 2.79]Regression, Logistic
Secondary
Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score
Participant in remission defined as HAM-A total score of \<= 7. HAM-A=clinician-rated interview measuring presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges 0 - 56; higher score indicates greater anxiety.
Time frame: Week 1 through Week 8
Population: Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment, and had a baseline and post-baseline efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 1 Remission: Yes | 12 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 1 Remission: No | 152 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 2 Remission: Yes | 22 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 2 Remission: No | 144 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 3 Remission: Yes | 32 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 3 Remission: No | 125 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 4 Remission: Yes | 43 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 4 Remission: No | 110 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 5 Remission: No | 96 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 6 Remission: Yes | 37 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 6 Remission: No | 85 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 8 Remission: Yes | 40 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 8 Remission: No | 86 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 8 (LOCF) Remission: Yes | 55 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 8 (LOCF) Remission: No | 122 participants |
| Pregabalin | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 5 Remission: Yes | 39 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 1 Remission: Yes | 5 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 5 Remission: No | 100 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 1 Remission: No | 164 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 8 Remission: No | 96 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 2 Remission: Yes | 15 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 6 Remission: Yes | 32 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 2 Remission: No | 148 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 8 (LOCF) Remission: No | 134 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 3 Remission: Yes | 18 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 6 Remission: No | 93 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 3 Remission: No | 142 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 8 (LOCF) Remission: Yes | 42 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 4 Remission: Yes | 29 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 8 Remission: Yes | 31 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 4 Remission: No | 121 participants |
| Placebo | Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score | Week 5 Remission: Yes | 30 participants |
Comparison: Week 195% CI: [0.94, 8.8]Regression, Logistic
Comparison: Week 295% CI: [0.72, 3.06]Regression, Logistic
Comparison: Week 395% CI: [1.09, 3.97]Regression, Logistic
Comparison: Week 495% CI: [0.99, 3.28]Regression, Logistic
Comparison: Week 595% CI: [0.82, 2.85]Regression, Logistic
Comparison: Week 695% CI: [0.71, 2.48]Regression, Logistic
Comparison: Week 895% CI: [0.85, 2.83]Regression, Logistic
Comparison: Week 8 Last Observation Carried Foward (LOCF)95% CI: [0.92, 2.53]Regression, Logistic
Secondary
Time to Onset of Sustained Hamilton Anxiety Rating Scale (HAM-A) Improvement
Time to sustained improvement was defined as time to 50% or greater reduction in HAM-A total score from Baseline, which was sustained for the remainder of the study. HAM-A is a clinician-rated interview measuring the presence of anxiety-related symptoms in 14 areas. Total score ranges from 0 to 56; a higher score indicates greater anxiety.
Time frame: Week 8
Population: Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment, and had a baseline and post-baseline efficacy assessment. CI for placebo patients was not estimable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pregabalin | Time to Onset of Sustained Hamilton Anxiety Rating Scale (HAM-A) Improvement | 57 days |
Comparison: Kaplan Meier product limit estimate for calculating median time in days to onset sustained HAM-A Improvement.p-value: 0.0137Log Rank