Pregabalin in the Treatment of Patients With Generalized Anxiety Disorder (GAD).

Study Overview
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Brief Summary
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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
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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.

Official Title
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An 8-Week, Double-Blind, Placebo-Controlled, Phase 3 Trial of Pregabalin (150-600 mg/Day) in the Adjunctive Treatment of Patients With Generalized Anxiety Disorder (GAD) Who Have Not Optimally Responded to Existing Therapies(GAD)

Conditions
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Generalized Anxiety Disorder

Intervention / Treatment
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* Drug: pregabalin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm 2<br> | Drug: placebo<br>* placebo + concurrent GAD treatment from the open-label study period<br>|
| Experimental: Arm 1<br> | Drug: pregabalin<br>* 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<br>* Other names: Lyrica;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Weeks 1 through Week 8 | 
| 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. | Weeks 1 through Week 8 | 
| 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. | Week 1 through Week 8 | 
| 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. | Week 8 | 
| 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). | Week 1 through Week 8 | 
| 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. | Week 8 | 
| 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. | Weeks 1 through Week 8 |