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.

Official Title: “A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Pregabalin in Subjects With Generalized Anxiety Disorder (GAD) Switching From Benzodiazepine Therapy.”

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.

Intervention(s) in this Clinical Trial

• Drug: Pregabalin
  • GAD subjects on stable dose of alprazolam will be randomized to double-blind pregabalin at starting dose of 75mg twice daily. Weekly assessments of tolerability, need for rescue medication, anxiety/withdrawal symptoms will guide flexible dose titration of pregabalin at dose range between 75 and 300mg twice daily. Subjects successful in discontinuation of alprazolam while treated with pregabalin will continue to be maintained on pregabalin for 6 weeks and assessed weekly for ability to remain in the study.
• Drug: Placebo
  • GAD subjects on stable dose of alprazolam will be randomized to double-blind placebo matching assessments and study medication titration as detailed under the pregabalin arm description. Subjects successful in discontinuation of alprazolam while treated with placebo will continue to be maintained on placebo for 6 weeks and assessed weekly for ability to remain in the study.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Pregabalin
  • Pregabalin treatment for GAD during 6 week taper/discontinuation from alprazolam treatment; followed by 6 weeks pregabalin treatment 'alprazolam free'.
• Placebo Comparator: Placebo
  • Placebo treatment of GAD during 6 week taper/discontinuation of alprazolam treatment followed by 6 weeks continuation of placebo treatment 'alprazolam free'.

Primary Measures

• 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
  • Time Frame: Endpoint (Post Alprazolam Free Week 6 or LOCF Post Alprazolam Free Week 1)
    Safety Issue?: No

Secondary Measures

• Mean Change From Baseline in Hamilton Anxiety Scale (HAM-A) Scores
  • Time Frame: Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (Alprazolam Free [AF] Week 6)
    Safety Issue?: No
• Number of Subjects With > = 6 Point Increase in Physician's Withdrawal Checklist (PWC) Scores
  • Time Frame: Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)
    Safety Issue?: No
• Number of Subjects With > = 5 New PWC Symptoms
  • Time Frame: Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)
    Safety Issue?: No
• Mean Change From Baseline in Physician's Withdrawal Checklist (PWC) Scores
  • Time Frame: Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)
    Safety Issue?: No
• Mean Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Scores.
  • Time Frame: Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )
    Safety Issue?: No
• Mean Scores for Clinical Global Impression-Improvement (CGI-I) Scale
  • Time Frame: Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )
    Safety Issue?: No
• Mean Scores for Patient Global Impression-Improvement (PGI-I)
  • Time Frame: Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )
    Safety Issue?: No
• Mean Change From Baseline in Digit Symbol Substitution Test (DSST) Scores
  • Time Frame: Baseline, Endpoint (AF Week 6 )
    Safety Issue?: No
• Time to Discontinuation
  • Time Frame: Baseline, Week 13 (Final Visit/Early Termination)
    Safety Issue?: Yes
• Time to First Use of Rescue Medication
  • Time Frame: Baseline, Week 13 (Final Visit/Early Termination)
    Safety Issue?: Yes
• Number of Subjects in Relapse Free State at 6-week Benzodiazepine-free Endpoint (Alprazolam Free Week 6)
  • Time Frame: Alprazolam Free Week 6
    Safety Issue?: No

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)

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Pfizer Industry

Overall Clinical Trial Officials and Contacts

Pfizer CT.gov Call Center Study Director Pfizer  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00368745

Study ID Number: A0081092

ClinicalTrials.gov Identifier: NCT00368745

Health Authority: Mexico: Secretaria de Salud de Mexico

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