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

Phase 3

Completed

• Conditions: Generalized Anxiety Disorder
• Interventions: Drug: Placebo; Drug: Pregabalin

• Registration Number: NCT00368745
• Lead Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Brief Summary

GAD subjects maintained on a stable dose of alprazolam for at least four weeks who meet eligibility criteria will be randomized to receive pregabalin vs matching placebo while simultaneously tapering off of alprazolam over 6 weeks. Subjects return weekly for assessment of safety/tolerability of pregabalin vs placebo as well as for assessment of anxiety and benzodiazepine withdrawal symptoms. Subjects successfully able to discontinue alprazolam, will continue 6 weeks of treatment with pregabalin vs placebo (free of benzodiazepine use). The efficacy and safety of pregabalin vs placebo for anxiety symptoms and ability to discontinue/remain free of alprazolam will be compared among pregabalin and placebo treated groups. Hypothesis is that a greater proportion of subjects will be successful in discontinuing and remaining free from benzodiazepines who were treated with pregabalin as compared to subjects treated with placebo.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2006-08-23
• Study First Submitted QC: 2006-08-23
• Study First Posted: 2006-08-25
• Study Start: 2006-09
• Primary Completion: 2008-08
• Study Completion: 2008-08
• Results First Submitted: 2009-08-10
• Results First Submitted QC: 2009-09-28
• Status Verified: 2009-11
• Results First Posted: 2009-11-09
• Last Update Submitted: 2021-01-21
• Last Update Posted: 2021-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

• Provide written informed consent
• 18-65 years old
• male and female
• A primary lifetime diagnosis of DSM-IV-TR (2000) GAD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition)

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Exclusion Criteria

• Pregnant or lactating women
• History of non-response to alprazolam, other benzodiazepines, gabapentin or pregabalin given for the treatment of anxiety as indicated by a (screening or baseline) Hamilton Anxiety Scale (HAM-A) score > 18

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo treatment of GAD during 6 week taper/discontinuation of alprazolam treatment followed by 6 weeks continuation of placebo treatment 'alprazolam free'.
Pregabalin	Pregabalin	Pregabalin treatment for GAD during 6 week taper/discontinuation from alprazolam treatment; followed by 6 weeks pregabalin treatment 'alprazolam free'.

Primary Outcome Measures

Name	Time	Method
Number of Subjects at Endpoint (Post Alprazolam Free Week 6 or Last Observation Carried Forward [LOCF] Post Alprazolam Free Week 1) Who Are Benzodiazepine Free	Endpoint (Post Alprazolam Free Week 6 or LOCF Post Alprazolam Free Week 1)	Number of subjects benzodiazepine free: \< 2 doses rescue medication; negative urine benzodiazepine psychoactive toxicology assay (each visit Alprazolam Free phase); negative serum benzodiazepine alcohol assay (endpoint or LOCF).

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Physician's Withdrawal Checklist (PWC) Scores	Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)	PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Change from baseline not analyzed as PWC was not measured at baseline. Mean PWS scores presented in Post-hoc outcome measure Mean PWS scores.
Mean Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Scores.	Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )	CGI-S: 7-point scale to assess global change in subject condition compared to baseline; range 1 (no evidence of illness) to 7 (among the most severely ill); higher score = more affected. Change from baseline: mean at observation minus mean at baseline.
Time to First Use of Rescue Medication	Baseline, Week 13 (Final Visit/Early Termination)	The 25th percentile estimate of time until first use of rescue medication is based on Kaplan-Meier estimates. Event day is the study day when the subject first used rescue medication. Rescue medication: packet with 2 doses alprazolam to take only in the event subject experiences severe symptoms of benzodiazepine withdrawal or rebound anxiety.
Mean Change From Baseline in Hamilton Anxiety Scale (HAM-A) Scores	Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (Alprazolam Free [AF] Week 6)	HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); lower score indicates less affected. Change from baseline: mean at observation minus mean at baseline.
Number of Subjects With > = 5 New PWC Symptoms	Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)	PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Data not analyzed: PWC not measured at baseline.
Time to Discontinuation	Baseline, Week 13 (Final Visit/Early Termination)	The 25th percentile estimate of time until discontinuation is based on Kaplan-Meier estimates. Event day is the study day when the subject discontinued from study.
Number of Subjects With > = 6 Point Increase in Physician's Withdrawal Checklist (PWC) Scores	Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)	PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Data not analyzed: PWC not measured at baseline.
Mean Scores for Clinical Global Impression-Improvement (CGI-I) Scale	Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )	CGI-I: 7-point scale to assess global change in subject condition compared to baseline; range 1 (very much improved) to 7 (very much worse); higher score = more affected.
Mean Scores for Patient Global Impression-Improvement (PGI-I)	Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )	PGI-I: subject rated 7-point scale measures change in overall status; range 1 (very much improved) to 7 (very much worse).
Mean Change From Baseline in Digit Symbol Substitution Test (DSST) Scores	Baseline, Endpoint (AF Week 6 )	DSST: subject-rated; evaluates aspects of cognition (includes attending to directions, processing speed, sustained attention, visual-motor integration, learning and psychomotor speed). Subject matches symbol (1 to 9) with corresponding number key (1 to 9); number of correct symbol-number pairs completed by subject over a 90-second test period determines DSST score. Change: mean at observation minus mean at baseline. Data summarized as change from baseline to endpoint.
Number of Subjects in Relapse Free State at 6-week Benzodiazepine-free Endpoint (Alprazolam Free Week 6)	Alprazolam Free Week 6	Number of subjects benzodiazepine free: \< 2 doses rescue medication; negative urine toxicology assay (each visit Alprazolam Free phase), negative urine alcohol assay (Alprazolam Free Week 6 = endpoint or LOCF). Relapse: \> = 2 intakes rescue medication, positive urine and /or alcohol assays, unable to tolerate alprazolam taper, or discontinuation.

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇪🇸 Zamora, Spain