Study Evaluating The Safety And Efficacy Of Varenicline and Bupropion For Smoking Cessation In Subjects With And Without A History Of Psychiatric Disorders
- Conditions
- Smoking Cessation
- Interventions
- Registration Number
- NCT01456936
- Lead Sponsor
- Pfizer
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 8144
- 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.
-
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo 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. varenicline varenicline tartrate - bupropion bupropion hydrochloride - Nicotine Replacement Therapy Patch Nicotine Replacement Therapy Patch -
- Primary Outcome Measures
Name Time Method Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint 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 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 Outcome Measures
Name Time Method 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. The 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. Each of these 16 components is reported below.
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. The 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. Each of these 16 components is reported below.
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. The NPS AE composite results (as previously described) are for the two cohorts combined and are presented below.
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. 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. Only those events rated as severe are reported; this excludes any moderate events in the primary NPS AE endpoint.
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. The 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. Only those events rated as severe are reported; this excludes any moderate events in the primary NPS AE endpoint.
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. The 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. Only those events rated as severe are reported; this excludes any moderate events in the primary NPS AE endpoint.
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. The NPS AE endpoint was the occurrence of at least 1 treatment-emergent "severe" AE of anxiety, depression, feeling abnormal, or hostility and/or the occurrence of at least 1 treatment-emergent "severe" AE of agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior, or completed suicide. Only those events rated as severe are reported; this excludes any moderate events in the primary NPS AE endpoint.
Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort Baseline to Week 24 The HADS is a subject self-reporting scale completed in person at clinic visits at Baseline and Weeks 1 through 6, 8, 10, 12, 13, 16, 20, and 24. It contains 14 individual item responses ranging in increasing severity from 0 (normal) to 3 (most severe) for a total range of 0 to 42. Of the 14 items, 7 assess anxiety and 7 assess depression, providing 2 subscales with ranges of 0 to 21. For each subscale, 0 to 7 is considered normal, while 15 to 21 represents severe symptoms.
HADS Total Score, Psychiatric History Cohort Baseline to Week 24 The HADS is a subject self-reporting scale completed in person at clinic visits at Baseline and Weeks 1 through 6, 8, 10, 12, 13, 16, 20, and 24. It contains 14 individual item responses ranging in increasing severity from 0 (normal) to 3 (most severe) for a total range of 0 to 42. Of the 14 items, 7 assess anxiety and 7 assess depression, providing 2 subscales with ranges of 0 to 21. For each subscale, 0 to 7 is considered normal, while 15 to 21 represents severe symptoms.
HADS Total Score (Overall) Baseline to Week 24 The HADS is a subject self-reporting scale completed in person at clinic visits at Baseline and Weeks 1 through 6, 8, 10, 12, 13, 16, 20, and 24. It contains 14 individual item responses ranging in increasing severity from 0 (normal) to 3 (most severe) for a total range of 0 to 42. Of the 14 items, 7 assess anxiety and 7 assess depression, providing 2 subscales with ranges of 0 to 21. For each subscale, 0 to 7 is considered normal, while 15 to 21 represents severe symptoms.
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. The C-SSRS is a semi-structured interview designed to evaluate an individual's degree of suicidal ideation, preparatory acts or behavior to actual attempt, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent". Answers at screening are for lifetime history. Answers for all other visits are since last visit.The scale is also used to record any completed suicides.
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. The C-SSRS is a semi-structured interview designed to evaluate an individual's degree of suicidal ideation, preparatory acts or behavior to actual attempt, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent". Answers at screening are for lifetime history. Answers for all other visits are since last visit. The scale is also used to record any completed suicides.
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. The C-SSRS is a semi-structured interview designed to evaluate an individual's degree of suicidal ideation, preparatory acts or behavior to actual attempt, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent". Answers at screening are for lifetime history. Answers for all other visits are since last visit. The scale is also used to record any completed suicides.
Clinical Global Impression of Improvement (CGI-I), "No Change" Rating by Visit Baseline to Week 24 The CGI-I is a clinician rated instrument that measures change in participant's psychiatric condition (or lack thereof in the stratum without psychiatric disorders) on a 7 point scale ranging from 1 (very much improved) to 7 (very much worse), with 4 = no change. The ratings were applicable even to those without psychiatric diagnoses (eg, those with no psychiatric symptoms would be rated as "normal, not at all ill" on the CGI-S at baseline and assuming no psychiatric symptoms emerge during the trial, would be rated as "no change" on the CGI-I at follow-up visits). For those participants with a psychiatric diagnosis, the clinician should rate the severity of the mental illness with respect to the clinician's experience with the psychiatric population to which the participant belongs.
CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Non-psychiatric History Cohort Week 9 through Week 12 A responder to this endpoint requires the answer "no" to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 12 (inclusive).
CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Psychiatric History Cohort Week 9 through Week 12 A responder to this endpoint requires the answer "no" to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 12 (inclusive).
CO-Confirmed Continuous Abstinence for Weeks 9 Through 12 (Overall) Week 9 through Week 12 A responder to this endpoint requires the answer "no" to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 12 (inclusive).
CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Non-psychiatric History Cohort Week 9 through Week 24 A responder to this endpoint requires the answer "no" to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 24 (inclusive).
CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Psychiatric History Cohort Week 9 through Week 24 A responder to this endpoint requires the answer "no" to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 24 (inclusive).
CO-confirmed Continuous Abstinence From Week 9 Through Week 24 (Overall) Week 9 through Week 24 A responder to this endpoint requires the answer "no" to both questions 1 and 2 on the Nicotine Use Inventory at every visit from Week 9 to Week 24 (inclusive).
7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort 24 Weeks A responder to this endpoint requires the answer "no" to both questions 3 and 6 on the nicotine use inventory at that specific visit.
NUI Question 3 (Baseline through Week 24): Has the subject smoked any cigarettes (even a puff) in the last 7 days? NUI Question 6 (Baseline through Week 12): Has the subject used any other nicotine containing products in the last 7 days? NUI Question 6 (Week 13 through Week 24): Has the subject used any other tobacco products in the last 7 days?7-Day Point Prevalence of Abstinence, Psychiatric History Cohort 24 Weeks A responder to this endpoint requires the answer "no" to both questions 3 and 6 on the nicotine use inventory at that specific visit.
NUI Question 3 (Baseline through Week 24): Has the subject smoked any cigarettes (even a puff) in the last 7 days? NUI Question 6 (Baseline through Week 12): Has the subject used any other nicotine containing products in the last 7 days? NUI Question 6 (Week 13 through Week 24): Has the subject used any other tobacco products in the last 7 days?7-Day Point Prevalence of Abstinence (Overall) 24 Weeks A responder to this endpoint requires the answer "no" to both questions 3 and 6 on the nicotine use inventory at that specific visit.
NUI Question 3 (Baseline through Week 24): Has the subject smoked any cigarettes (even a puff) in the last 7 days? NUI Question 6 (Baseline through Week 12): Has the subject used any other nicotine containing products in the last 7 days? NUI Question 6 (Week 13 through Week 24): Has the subject used any other tobacco products in the last 7 days?
Trial Locations
- Locations (151)
Coastal Clinical Research, Inc.
🇺🇸Mobile, Alabama, United States
NoesisPharma Research
🇺🇸Phoenix, Arizona, United States
Pharmacology Research Institute
🇺🇸Newport Beach, California, United States
Synergy Clinical Research of Escondido
🇺🇸Escondido, California, United States
Sun Valley Research Center
🇺🇸Imperial, California, United States
Omega Clinical Trials
🇺🇸La Habra, California, United States
Pacific Treatment and Research Center UC San Diego Health System
🇺🇸La Jolla, California, United States
David Geffen School of Medicine at University of California, Los Angeles
🇺🇸Los Angeles, California, United States
North County Clinical Research
🇺🇸Oceanside, California, United States
Neuropsychiatric Research Center of Orange County
🇺🇸Orange, California, United States
Scroll for more (141 remaining)Coastal Clinical Research, Inc.🇺🇸Mobile, Alabama, United States