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

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)

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.

Study Overview

• Status: Completed
• Conditions: Generalized Anxiety Disorder
• Intervention / Treatment: Drug: placebo; Drug: pregabalin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 356
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 602 00
    • Pfizer Investigational Site
  • Litomerice, Czechia, 412 01
    • Pfizer Investigational Site
  • Praha 2, Czechia, 120 00
    • Pfizer Investigational Site
  • Praha 5, Czechia, 158 00
    • Pfizer Investigational Site
  • Praha 6, Czechia, 163 00
    • Pfizer Investigational Site
  • Praha 8 - Bohnice, Czechia, 181 03
    • Pfizer Investigational Site
• Estonia
  • Tallinn, Estonia, 10614
    • Pfizer Investigational Site
  • Tartu, Estonia, 50417
    • Pfizer Investigational Site
  • Viljandi Mk.
    • Viljandi, Viljandi Mk., Estonia, 71024
      • Pfizer Investigational Site
• Finland
  • Helsinki, Finland, 00029 HUS
    • Pfizer Investigational Site
  • Joensuu, Finland, 80100
    • Pfizer Investigational Site
  • Kuopio, Finland, 70110
    • Pfizer Investigational Site
• Hungary
  • Budapest, Hungary, 1137
    • Pfizer Investigational Site
  • Budapest, Hungary, 1083
    • Pfizer Investigational Site
  • Pecs, Hungary, 7623
    • Pfizer Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 115522
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 119034
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 123367
    • Pfizer Investigational Site
  • Smolensk, Russian Federation, 214019
    • Pfizer Investigational Site
  • Smolensk, Russian Federation, 214018
    • Pfizer Investigational Site
  • St Petersburg, Russian Federation, 190121
    • Pfizer Investigational Site
  • St. Petersburg, Russian Federation, 192019
    • Pfizer Investigational Site
  • St. Petersburg, Russian Federation, 191180
    • Pfizer Investigational Site
• Serbia
  • Belgrade, Serbia, 11000
    • Pfizer Investigational Site
  • Belgrade, Serbia, 11 000
    • Pfizer Investigational Site
  • Belgrade, Serbia
    • Pfizer Investigational Site
  • Kragujevac, Serbia, 34000
    • Pfizer Investigational Site
• Ukraine
  • Dnipropetrovsk, Ukraine, 49005
    • Pfizer Investigational Site
  • Dnipropetrovsk, Ukraine, 49115
    • Pfizer Investigational Site
  • Donetsk, Ukraine, 83037
    • Pfizer Investigational Site
  • Kyiv, Ukraine, 01030
    • Pfizer Investigational Site
  • Lugansk, Ukraine, 91045
    • Pfizer Investigational Site
  • Lviv, Ukraine, 79021
    • Pfizer Investigational Site
• United States
  • California
    • Arcadia, California, United States, 91007-3462
      • Pfizer Investigational Site
    • Burbank, California, United States, 91506
      • Pfizer Investigational Site
    • Redlands, California, United States, 92374
      • Pfizer Investigational Site
    • Sherman Oaks, California, United States, 91403
      • Pfizer Investigational Site
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Pfizer Investigational Site
  • Florida
    • Destin, Florida, United States, 32541
      • Pfizer Investigational Site
    • Fort Walton Beach, Florida, United States, 32547
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33143
      • Pfizer Investigational Site
    • South Miami, Florida, United States, 33143
      • Pfizer Investigational Site
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Pfizer Investigational Site
    • Wichita, Kansas, United States, 67207
      • Pfizer Investigational Site
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Pfizer Investigational Site
    • Shreveport, Louisiana, United States, 71104
      • Pfizer Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Pfizer Investigational Site
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
      • Pfizer Investigational Site
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • Pfizer Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Pfizer Investigational Site
  • New Jersey
    • Clementon, New Jersey, United States, 08021
      • Pfizer Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10128-1708
      • Pfizer Investigational Site
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45227
      • Pfizer Investigational Site
    • Cleveland, Ohio, United States, 44109-1998
      • Pfizer Investigational Site
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Pfizer Investigational Site
    • Media, Pennsylvania, United States, 19063
      • Pfizer Investigational Site
    • Philadelphia, Pennsylvania, United States, 19136
      • Pfizer Investigational Site
    • Philadelphia, Pennsylvania, United States, 19104-3309
      • Pfizer Investigational Site
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Pfizer Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38133
      • Pfizer Investigational Site
    • Memphis, Tennessee, United States, 38117
      • Pfizer Investigational Site
  • Texas
    • Houston, Texas, United States, 77008
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77074
      • Pfizer Investigational Site
    • Lake Jackson, Texas, United States, 77566
      • Pfizer Investigational Site
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188-1660
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Rickels K, Shiovitz TM, Ramey TS, Weaver JJ, Knapp LE, Miceli JJ. Adjunctive therapy with pregabalin in generalized anxiety disorder patients with partial response to SSRI or SNRI treatment. Int Clin Psychopharmacol. 2012 May;27(3):142-50. doi: 10.1097/YIC.0b013e328350b133.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: December 15, 2006
• First Submitted That Met QC Criteria: December 18, 2006
• First Posted (Estimate): December 19, 2006

Study Record Updates

• Last Update Posted (Actual): February 10, 2021
• Last Update Submitted That Met QC Criteria: January 21, 2021
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: A0081103