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 pregablin vs placebo as well as for assessment of anxiety and benzodiazepine withdrawal symptoms. Subjects sucessfully able to discontinue alprazolam, will continue 6 weeks of treatment with pregabalin vs placebo (free of benzodiazepine use). The efficacy and safety of pregablin vs placebo for anxiety symptoms and ability to discontinue/remain free of alprazolam will be compared among pregablin 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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2008

Intervention(s) in this Clinical Trial

• Drug: Pregablin
  • GAD subjects on stable dose of alprazolam will be randomized to pregabalin vs matching placebo 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 vs placebo at dose range between 75 and 300 twice daily. Subjects successful in discontinuation of alprazolam while treated with placebo vs pregabalin will continue to be maintained on their randomized medication for 6 weeks and assessed weekly for ability to remain "alprazolam free'. After 12 weeks on placebo vs pregabalin or endpoint,re-assessment of baseline measures followed by one week taper off placebo vs pregabalin will occur.
• Other: Placebo
  • GAD subjects on stable dose of alprazolam will be randomized to pregabalin vs matching placebo 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 vs placebo at dose range between 75 and 300 twice daily. Subjects successful in discontinuation of alprazolam while treated with placebo vs pregabalin will continue to be maintained on their randomized medication for 6 weeks and assessed weekly for ability to remain "alprazolam free'. After 12 weeks on placebo vs pregabalin or endpoint,re-assessment of baseline measures followed by one week taper off placebo vs pregabalin will occur.

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: Treatment
  • Placebo treatment of GAD during 6 week taper/discontinuation of alprazolam treatment followed by 6 weeks continuation of placebo treatment 'alprazolam free'.

Primary Measures

• Negative urine benzodiazepine/psychoactive toxicology assay (done at each visit of the Alprazolam-Free Phase of Double-Blind Treatment) and negative serum benzodiazepine/alcohol assay (done at endpoint).
  • Time Frame: 6 weeks
    Safety Issue?: No
• Efficacy/Safety: Following taper and discontinuation from stable benzodiazepine treatment,the proportion of subjects treated with pregabalin who remain 6 weeks free from benzodiazepine use compared to subjects treated with placebo.
  • Time Frame: 6 weeks
    Safety Issue?: No
• Negative benzodiazepine use defined as negative labs for benzodiazepines as well not requiring use of 'rescue' alprazolam packet between visits
  • Time Frame: 6 weeks
    Safety Issue?: Yes

Secondary Measures

• Proportion of subjects with > 6 point increase in PWC scores compared to baseline or compared to a previous week in the 6 week benzodiazepine free period.
  • Time Frame: weeks 0, 6-13
    Safety Issue?: Yes
• Proportion of subjects with > 5 new PWC symptoms between weekly visits during the benzodiazepine free 6 week period or between a weekly visit and baseline visit.
  • Time Frame: weeks 0, 6-13
    Safety Issue?: Yes
• Mean change between 'randomization/baseline' score of Clinical Global Impression Severity (CGI-S) and weekly scores of CGI-S.
  • Time Frame: weeks 0-13
    Safety Issue?: No
• Amount of time 'relapse free' among treatment groups during 6 week 'benzodiazepine free'phase (Relapse free-defined as negative labs for benzodiazepines and not requiring more than allowed rescue benzodiazepine medication between visits)
  • Time Frame: weeks 6-13
    Safety Issue?: No
• Mean 'Patient Global Impression-Improvement' (PGI-I) score at each visit.
  • Time Frame: week 1-13
    Safety Issue?: No
• Mean Clinician Global Impression-Improvement (CGI-I) score at each visit.
  • Time Frame: weeks 1-13
    Safety Issue?: No
• Time until first subject needs to take "rescue medication"
  • Time Frame: days 1-91
    Safety Issue?: Yes
• Mean change in weekly 'Physician Withdrawal Checklist' (PWC) scores compared to randomization /baseline
  • Time Frame: weeks 0-13
    Safety Issue?: Yes
• Mean change from randomization /baseline to endpoint in 'Digit Symbol Substitution Test'(DSST) scores
  • Time Frame: week 0, 13
    Safety Issue?: No
• Mean change in weekly anxiety scores compared to baseline (measured by Hamilton Anxiety Scale or HAM-A)
  • Time Frame: weeks 0-13
    Safety Issue?: No
• Time until subject discontinuation (inability to tolerate benzodiazepine taper or free state)
  • Time Frame: days 1-91
    Safety Issue?: Yes

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, gabapentine 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 Sponsor: Pfizer

Overall Clinical Trial Officials and Contacts

Pfizer CT.gov Call Center Study Director Pfizer  

Overall Contact: Pfizer CT.gov Call Center 1-800-718-1021 

Information obtained from ClinicalTrials.gov on September 05, 2008

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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