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

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety and efficacy in patients with generalized anxiety disorder after short- (3 months) and long-term (6 months) use of Pregabalin (Lyrica).

Official Title
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Long Term Safety And Efficacy Study Of Pregabalin (Lyrica) In Subjects With Generalized Anxiety Disorder

Conditions
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Generalized Anxiety Disorder

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Lorazepam
* Drug: Pregabalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis Generalized Anxiety Disorder HAM-A score >=18 and HAM-D (item 1) score >=2 at screening and baseline Needs pharmacological treatment Exclusion Criteria: Current or past diagnosis of any other DSM IV Axis I disorders A history of failed treatment with a benzodiazepine Any clinically significant, serious, or unstable hematologic, autoimmune, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Experimental: 1<br> | Drug: Pregabalin<br>* Pregabalin 150-300 mg given twice a day<br>* Other names: Lyrica;|
| Active Comparator: 2<br> | Drug: Lorazepam<br>* Lorazepam 3-4 mg given twice a day<br>|
| Experimental: 3<br> | Drug: Pregabalin<br>* Pregabalin 450-600 mg given twice a day<br>* Other names: Lyrica;|
| Placebo Comparator: 4<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Baseline, Week 1 post-treatment discontinuation (discontinuation occurred prior to Week 9) | 
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Baseline, Week 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) | 
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Baseline, Week 1 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | 
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Baseline, Week 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | 
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Baseline, Week 1 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | 
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. | Baseline, Week 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | 
| Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. | Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred prior to Week 9) | 
| Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2 | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. | Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) | 
| Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. | Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | 
| Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2 | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. | Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | 
| Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. | Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | 
| Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. | Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Rebound Anxiety for Cohort 1 (Less Than 3-Month Last Visit) | Rebound anxiety was defined as a rapid return of the participant's original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value. | 2 weeks post-treatment discontinuation (discontinuation occurred prior to Week 9) | 
| Number of Participants With Rebound Anxiety for Cohort 2 (3-Month Last Visit) | Rebound anxiety was defined as a rapid return of the participant's original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value. | 2 weeks post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | 
| Number of Participants With Rebound Anxiety for Cohort 3 (6-Month Last Visit) | Rebound anxiety was defined as a rapid return of the participant's original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value. | 2 weeks post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | 
| Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 1 (Less Than 3-Month Last Visit) | DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2. | 2 weeks post-treatment discontinuation (discontinuation occurred prior to Week 9) | 
| Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 2 (3-Month Last Visit) | DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2. | 2 weeks post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | 
| Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) | DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2. | 2 weeks post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | 
| Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. | Baseline, Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) | 
| Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. | Baseline, Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | 
| Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. | Baseline, Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24) | 
| Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. | Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) | 
| Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. | Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | 
| Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) | PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. | Week 1, 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) | 
| Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) | 
| Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. | Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | 
| Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24) | 
| Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) | 
| Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. | Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) | 
| Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24) | 
| Hamilton Anxiety Scale (HAM-A) Score for Period 1 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Baseline, Week 12 | 
| Hamilton Anxiety Scale (HAM-A) Score for Period 2 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Baseline, Week 24 | 
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 12 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Baseline, Week 12 | 
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 24 | HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. | Baseline, Week 24 | 
| Clinical Global Impression - Severity (CGI-S) Score for Period 1 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. | Baseline, Week 12 | 
| Clinical Global Impression - Severity (CGI-S) Score for Period 2 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected | Baseline, Week 24 | 
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 12 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. | Baseline, Week 12 | 
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 24 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected | Baseline, Week 24 | 
| Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 1 | CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. | Week 12 | 
| Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 2 | CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. | Week 24 |