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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00624780
First received: February 15, 2008
Last updated: March 5, 2013
Last verified: September 2012
  Purpose

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).


Condition Intervention Phase
Generalized Anxiety Disorder
Drug: Pregabalin
Drug: Lorazepam
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Long Term Safety And Efficacy Study Of Pregabalin (Lyrica) In Subjects With Generalized Anxiety Disorder

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 [ Time Frame: Baseline, Week 1 post-treatment discontinuation (discontinuation occurred prior to Week 9) ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2 [ Time Frame: Baseline, Week 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 [ Time Frame: Baseline, Week 1 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2 [ Time Frame: Baseline, Week 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 [ Time Frame: Baseline, Week 1 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 [ Time Frame: Baseline, Week 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred prior to Week 9) ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) ] [ Designated as safety issue: Yes ]
    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.

  • Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 [ Time Frame: Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) ] [ Designated as safety issue: Yes ]
    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.

  • Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2 [ Time Frame: Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) ] [ Designated as safety issue: Yes ]
    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.

  • Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 [ Time Frame: Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) ] [ Designated as safety issue: Yes ]
    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.

  • Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2 [ Time Frame: Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Rebound Anxiety for Cohort 1 (Less Than 3-Month Last Visit) [ Time Frame: 2 weeks post-treatment discontinuation (discontinuation occurred prior to Week 9) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Rebound Anxiety for Cohort 2 (3-Month Last Visit) [ Time Frame: 2 weeks post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Rebound Anxiety for Cohort 3 (6-Month Last Visit) [ Time Frame: 2 weeks post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 1 (Less Than 3-Month Last Visit) [ Time Frame: 2 weeks post-treatment discontinuation (discontinuation occurred prior to Week 9) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 2 (3-Month Last Visit) [ Time Frame: 2 weeks post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit) [ Time Frame: 2 weeks post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Baseline, Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2 [ Time Frame: Baseline, Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2 [ Time Frame: Baseline, Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24) ] [ Designated as safety issue: Yes ]
    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.

  • Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) [ Time Frame: Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) ] [ Designated as safety issue: Yes ]
    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.

  • Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) [ Time Frame: Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) ] [ Designated as safety issue: Yes ]
    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.

  • Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) [ Time Frame: Week 1, 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24) ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24) ] [ Designated as safety issue: Yes ]
    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.

  • Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) [ Time Frame: Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9) ] [ Designated as safety issue: Yes ]
    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.

  • Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) [ Time Frame: Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15) ] [ Designated as safety issue: Yes ]
    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.

  • Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit) [ Time Frame: Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24) ] [ Designated as safety issue: Yes ]
    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.

  • Hamilton Anxiety Scale (HAM-A) Score for Period 1 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Hamilton Anxiety Scale (HAM-A) Score for Period 2 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Clinical Global Impression - Severity (CGI-S) Score for Period 1 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Clinical Global Impression - Severity (CGI-S) Score for Period 2 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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

  • Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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

  • Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 1 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.

  • Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 2 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Sheehan-Suicidality Tracking Scale (S-STS) Score [ Time Frame: Baseline up to Week 24 ] [ Designated as safety issue: No ]
    Sheehan-Suicidality Tracking Scale (S-STS): an 8-item prospective rating scale that tracked treatment-emergent suicidal ideation and behaviors. Items 1a, 2-6, 7a, and 8 were scored on a 5-point Likert scale (ranging from 0= not at all to 4=extremely). Items 1, 1b, and 7 required yes or no responses. Total score ranged from 0 to 35, higher score indicated higher suicidal tendency.

  • Number of Participants With Treatment-Emergent Adverse Events (AEs) [ Time Frame: Baseline up to Week 12 (period 1), Week 13 up to Week 24 (period 2) ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and Week 12, for period 1, and between Week 13 and Week 24, for period 2, that were absent before treatment or that worsened relative to pretreatment state.


Enrollment: 615
Study Start Date: May 2009
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Pregabalin
Pregabalin 150-300 mg given twice a day
Other Name: Lyrica
Active Comparator: 2 Drug: Lorazepam
Lorazepam 3-4 mg given twice a day
Experimental: 3 Drug: Pregabalin
Pregabalin 450-600 mg given twice a day
Other Name: Lyrica
Placebo Comparator: 4 Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00624780

  Show 57 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00624780     History of Changes
Other Study ID Numbers: A0081147
Study First Received: February 15, 2008
Results First Received: March 5, 2013
Last Updated: March 5, 2013
Health Authority: Finland: National Agency of Medicines (Lääkelaitos)

Additional relevant MeSH terms:
Anxiety Disorders
Mental Disorders
Pregabalin
Lorazepam
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Calcium Channel Blockers
Membrane Transport Modulators
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 28, 2014