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Study Evaluating The Safety And Efficacy Of Varenicline and Bupropion For Smoking Cessation In Subjects With And Without A History Of Psychiatric Disorders (EAGLES)

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01456936
First received: October 14, 2011
Last updated: May 9, 2016
Last verified: May 2016
  Purpose
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).

Condition Intervention Phase
Smoking Cessation
Drug: Placebo
Drug: varenicline tartrate
Drug: bupropion hydrochloride
Drug: Nicotine Replacement Therapy Patch
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: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: Yes ]
    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:
  • Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort [ Time Frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Week 9 through Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 9 through Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 9 through Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 9 through Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 9 through Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 9 through Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]

    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 [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]

    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) [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]

    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?



Enrollment: 8144
Study Start Date: November 2011
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 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.
Drug: Placebo
Triple dummy placebo for each treatment arm
Active Comparator: varenicline Drug: varenicline tartrate
Subjects will be titrated to the full dose during the first week in the following manner: 0.5 mg (tablet form) once a day for 3 days, 0.5 mg twice a day for 4 days, then 1 mg twice a day for 11 weeks
Other Name: Chantix; Champix
Active Comparator: bupropion Drug: bupropion hydrochloride
Subjects will receive 150 mg (tablet form) once a day for 3 days and then will take 150 mg twice a day for the remainder of the treatment period (11 weeks and 4 days).
Active Comparator: Nicotine Replacement Therapy Patch Drug: Nicotine Replacement Therapy Patch
Subjects will start active dosing the morning of the Week 1 visit and will receive a 21 mg transdermal patch per day x 7 weeks, followed by a 14 mg transdermal patch per day x 2 weeks, and then a 7 mg transdermal patch x 2 weeks for a total of 11 weeks of treatment.
Other Name: NRT

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)
  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: NCT01456936

  Show 156 Study Locations
Sponsors and Collaborators
Pfizer
GlaxoSmithKline
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01456936     History of Changes
Other Study ID Numbers: A3051123  2010-022914-15  EAGLES 
Study First Received: October 14, 2011
Results First Received: January 12, 2016
Last Updated: May 9, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
smoking cessation
psychiatric disease

Additional relevant MeSH terms:
Mental Disorders
Problem Behavior
Behavioral Symptoms
Nicotine
Varenicline
Bupropion
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Dopamine Agents
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 28, 2016