A Phase 4, Randomized, Double-blind, Active And Placebo-controlled, Multicenter Study Evaluating The Neuropsychiatric Safety And Efficacy Of 12 Weeks Varenicline Tartrate 1mg Bid And Bupropion Hydrochloride 150mg Bid For Smoking Cessation In Subjects With And Without A History Of Psychiatric Disorders
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Pfizer
- Enrollment
- 8,144
- Locations
- 151
- Primary Endpoint
- Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint
Study Overview
Brief Summary
This study is being conducted to assess varenicline and bupropion as aids to smoking cessation treatment in subjects with and without an established diagnosis of major psychiatric disorder and to characterize the neuropsychiatric safety profile (pre-specified adverse events (AEs) in both of these populations).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Male or female cigarette smokers, 18- 75 years, motivated to stop smoking and considered suitable for a smoking cessation attempt.
- •Smoked an average of at least 10 cigarettes per day during past year and during the month prior to the screening visit, and exhaled carbon monoxide (CO) >10 ppm at screening.
- •For Neuropsychiatric cohort- subjects must have proper diagnosis as outlined in protocol.
Exclusion Criteria
- •Subjects with a past or current diagnosis of one of the following disorders:
- •a. Psychotic Disorders:
- •Schizophreniform
- •Delusional Disorder
- •Psychotic Disorder NOS b. All Delirium, Dementia, and Amnestic and Other Cognitive Disorders c. All Substance Induced Disorders (Other than nicotine)
Arms & Interventions
varenicline
Intervention: varenicline tartrate (Drug)
placebo
Subjects randomized to placebo will receive placebo treatments for all three study drugs. Blinded placebo will be provided for varenicline, bupropion hydrochloride and transdermal nicotine patch (NRT). In addition, subjects will receive blinded placebo treatments for the study drugs they are not randomized to receive.
Intervention: Placebo (Drug)
bupropion
Intervention: bupropion hydrochloride (Drug)
Nicotine Replacement Therapy Patch
Intervention: Nicotine Replacement Therapy Patch (Drug)
Outcomes
Primary Outcomes
Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint
Time Frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
The primary safety endpoint is the occurrence of at least one treatment emergent "severe" adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent "moderate" or "severe" adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide.
Estimated NPS AE Rate (%), by Cohort
Time Frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
The primary safety endpoint is the occurrence of at least one treatment emergent "severe" adverse event of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least one treatment emergent "moderate" or "severe" adverse event of: agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Estimated NPS AE rate (%) was calculated based on least-squares means analysis.
Secondary Outcomes
- Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort(Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.)
- Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort(Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.)
- Occurrence of the Components of NPS AE Primary Endpoint (Overall)(Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.)
- Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort(Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.)
- Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort(Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.)
- Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort(Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.)
- Occurrence of the Components of Severe-only NPS AE Endpoint (Overall)(Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.)
- Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort(Baseline to Week 24)
- HADS Total Score, Psychiatric History Cohort(Baseline to Week 24)
- HADS Total Score (Overall)(Baseline to Week 24)
- Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort(Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.)
- Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort(Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.)
- Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall(Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.)
- Clinical Global Impression of Improvement (CGI-I), "No Change" Rating by Visit(Baseline to Week 24)
- CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Non-psychiatric History Cohort(Week 9 through Week 12)
- CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Psychiatric History Cohort(Week 9 through Week 12)
- CO-Confirmed Continuous Abstinence for Weeks 9 Through 12 (Overall)(Week 9 through Week 12)
- CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Non-psychiatric History Cohort(Week 9 through Week 24)
- CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Psychiatric History Cohort(Week 9 through Week 24)
- CO-confirmed Continuous Abstinence From Week 9 Through Week 24 (Overall)(Week 9 through Week 24)
- 7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort(24 Weeks)
- 7-Day Point Prevalence of Abstinence, Psychiatric History Cohort(24 Weeks)
- 7-Day Point Prevalence of Abstinence (Overall)(24 Weeks)