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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01456936




Registration number
NCT01456936
Ethics application status
Date submitted
14/10/2011
Date registered
21/10/2011
Date last updated
10/06/2016

Titles & IDs
Public title
Study Evaluating The Safety And Efficacy Of Varenicline and Bupropion For Smoking Cessation In Subjects With And Without A History Of Psychiatric Disorders
Scientific 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
Secondary ID [1] 0 0
2010-022914-15
Secondary ID [2] 0 0
A3051123
Universal Trial Number (UTN)
Trial acronym
EAGLES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Smoking Cessation 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - varenicline tartrate
Treatment: Drugs - bupropion hydrochloride
Treatment: Drugs - Nicotine Replacement Therapy Patch

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.

Active comparator: varenicline -

Active comparator: bupropion -

Active comparator: Nicotine Replacement Therapy Patch -


Treatment: Drugs: Placebo
Triple dummy placebo for each treatment arm

Treatment: Drugs: 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

Treatment: Drugs: 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).

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint
Timepoint [1] 0 0
Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Primary outcome [2] 0 0
Estimated NPS AE Rate (%), by Cohort
Timepoint [2] 0 0
Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Secondary outcome [1] 0 0
Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort
Timepoint [1] 0 0
Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Secondary outcome [2] 0 0
Occurrence of the Components of the NPS AE Primary Endpoint, Psychiatric History Cohort
Timepoint [2] 0 0
Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Secondary outcome [3] 0 0
Occurrence of the Components of NPS AE Primary Endpoint (Overall)
Timepoint [3] 0 0
Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Secondary outcome [4] 0 0
Occurrence of Severe-only NPS AEs in the Primary Endpoint, by Cohort
Timepoint [4] 0 0
Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Secondary outcome [5] 0 0
Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Non-psychiatric History Cohort
Timepoint [5] 0 0
Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Secondary outcome [6] 0 0
Occurrence of the Components of the Observed Severe-only NPS AE Primary Endpoint, Psychiatric History Cohort
Timepoint [6] 0 0
Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Secondary outcome [7] 0 0
Occurrence of the Components of Severe-only NPS AE Endpoint (Overall)
Timepoint [7] 0 0
Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Secondary outcome [8] 0 0
Hospital Anxiety and Depression Scale (HADS) Total Score, Non-psychiatric History Cohort
Timepoint [8] 0 0
Baseline to Week 24
Secondary outcome [9] 0 0
HADS Total Score, Psychiatric History Cohort
Timepoint [9] 0 0
Baseline to Week 24
Secondary outcome [10] 0 0
HADS Total Score (Overall)
Timepoint [10] 0 0
Baseline to Week 24
Secondary outcome [11] 0 0
Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort
Timepoint [11] 0 0
Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Secondary outcome [12] 0 0
Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Psychiatric History Cohort
Timepoint [12] 0 0
Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Secondary outcome [13] 0 0
Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Overall
Timepoint [13] 0 0
Lifetime, Baseline and Treatment-Emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Secondary outcome [14] 0 0
Clinical Global Impression of Improvement (CGI-I), "No Change" Rating by Visit
Timepoint [14] 0 0
Baseline to Week 24
Secondary outcome [15] 0 0
CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Non-psychiatric History Cohort
Timepoint [15] 0 0
Week 9 through Week 12
Secondary outcome [16] 0 0
CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Psychiatric History Cohort
Timepoint [16] 0 0
Week 9 through Week 12
Secondary outcome [17] 0 0
CO-Confirmed Continuous Abstinence for Weeks 9 Through 12 (Overall)
Timepoint [17] 0 0
Week 9 through Week 12
Secondary outcome [18] 0 0
CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Non-psychiatric History Cohort
Timepoint [18] 0 0
Week 9 through Week 24
Secondary outcome [19] 0 0
CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Psychiatric History Cohort
Timepoint [19] 0 0
Week 9 through Week 24
Secondary outcome [20] 0 0
CO-confirmed Continuous Abstinence From Week 9 Through Week 24 (Overall)
Timepoint [20] 0 0
Week 9 through Week 24
Secondary outcome [21] 0 0
7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort
Timepoint [21] 0 0
24 Weeks
Secondary outcome [22] 0 0
7-Day Point Prevalence of Abstinence, Psychiatric History Cohort
Timepoint [22] 0 0
24 Weeks
Secondary outcome [23] 0 0
7-Day Point Prevalence of Abstinence (Overall)
Timepoint [23] 0 0
24 Weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2015
Sample size
Target
Accrual to date
Final
8144
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [2] 0 0
Monash Alfred Psychiatry Research Centre - Melbourne
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
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United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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United States of America
State/province [3] 0 0
California
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United States of America
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Colorado
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Connecticut
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Florida
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Georgia
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Idaho
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Illinois
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Indiana
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Kansas
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Kentucky
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Louisiana
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Maine
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Massachusetts
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Minnesota
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Mississippi
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Missouri
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New Jersey
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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Tennessee
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Texas
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State/province [29] 0 0
Virginia
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United States of America
State/province [30] 0 0
Wisconsin
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Argentina
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Buenos Aires
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Brazil
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CE
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Brazil
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RS
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Brazil
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SP
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Bulgaria
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Bourgas
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Bulgaria
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Kazanlak
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Bulgaria
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Novi Iskar
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Bulgaria
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Pleven
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Bulgaria
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Plovdiv
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Bulgaria
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Ruse
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Bulgaria
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Sofia
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Bulgaria
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Troyan
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Canada
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Ontario
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Quebec
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Chile
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Maule
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Chile
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Valparaiso, V Region
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Denmark
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Ballerup
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Denmark
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Vejle
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Finland
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Espoo
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Finland
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Kuopio
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Finland
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Nummela
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Finland
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Oulu
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Finland
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Pori
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Finland
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Turku
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Germany
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Sachsen
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Germany
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Berlin
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Germany
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Freiburg
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Germany
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Hamburg
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Germany
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Muenchen
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Germany
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Tuebingen
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Mexico
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D.f.
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Mexico
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Mexico DF
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Mexico
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Michoacan
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Mexico
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Nuevo Leon
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New Zealand
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Rotorua
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Russian Federation
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Moscow
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Russian Federation
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Nizhni Novgorod
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Russian Federation
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Saint-Petersburg
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Russian Federation
State/province [69] 0 0
Smolensk
Country [70] 0 0
Russian Federation
State/province [70] 0 0
St. Petersburg
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Slovakia
State/province [71] 0 0
Bratislava
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Slovakia
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Levice
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Slovakia
State/province [73] 0 0
Rimavska Sobota
Country [74] 0 0
Slovakia
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Roznava
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South Africa
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Cape Town
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South Africa
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Gauteng
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South Africa
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Kwa-Zulu Natal
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South Africa
State/province [78] 0 0
Kwazulu Natal
Country [79] 0 0
South Africa
State/province [79] 0 0
Western Cape
Country [80] 0 0
Spain
State/province [80] 0 0
Barcelona
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Spain
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Caceres
Country [82] 0 0
Spain
State/province [82] 0 0
Madrid
Country [83] 0 0
Spain
State/province [83] 0 0
Zaragoza

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
GlaxoSmithKline
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT01456936
Trial related presentations / publications
Tonnesen P, Lawrence D, Tonstad S. Medication-assisted quit rates in participants with smoking-related diseases in EAGLES: Post hoc analyses of a double-blind, randomized, placebo-controlled clinical trial. Tob Induc Dis. 2022 May 10;20:46. doi: 10.18332/tid/146567. eCollection 2022.
Cinciripini PM, Kypriotakis G, Green C, Lawrence D, Anthenelli RM, Minnix J, Blalock JA, Beneventi D, Morris C, Karam-Hage M. The effects of varenicline, bupropion, nicotine patch, and placebo on smoking cessation among smokers with major depression: A randomized clinical trial. Depress Anxiety. 2022 May;39(5):429-440. doi: 10.1002/da.23259.
Ebbert JO, Jimenez-Ruiz C, Dutro MP, Fisher M, Li J, Hays JT. In Reply: Changing the Culture of Tobacco Dependence Treatment Among Not Only Patients, But Also Prescribers. Mayo Clin Proc. 2021 Sep;96(9):2495. doi: 10.1016/j.mayocp.2021.07.010. No abstract available.
Ebbert J, Jimenez-Ruiz C, Dutro MP, Fisher M, Li J, Hays JT. Frequently Reported Adverse Events With Smoking Cessation Medications: Post Hoc Analysis of a Randomized Trial. Mayo Clin Proc. 2021 Jul;96(7):1801-1811. doi: 10.1016/j.mayocp.2020.10.046. Epub 2021 Jun 8.
Beard E, Jackson SE, Anthenelli RM, Benowitz NL, Aubin LS, McRae T, Lawrence D, Russ C, Krishen A, Evins AE, West R. Estimation of risk of neuropsychiatric adverse events from varenicline, bupropion and nicotine patch versus placebo: secondary analysis of results from the EAGLES trial using Bayes factors. Addiction. 2021 Oct;116(10):2816-2824. doi: 10.1111/add.15440. Epub 2021 Apr 22.
Correa JB, Lawrence D, McKenna BS, Gaznick N, Saccone PA, Dubrava S, Doran N, Anthenelli RM. Psychiatric Comorbidity and Multimorbidity in the EAGLES Trial: Descriptive Correlates and Associations With Neuropsychiatric Adverse Events, Treatment Adherence, and Smoking Cessation. Nicotine Tob Res. 2021 Aug 29;23(10):1646-1655. doi: 10.1093/ntr/ntab056.
Nollen NL, Ahluwalia JS, Sanderson Cox L, Okuyemi K, Lawrence D, Samuels L, Benowitz NL. Assessment of Racial Differences in Pharmacotherapy Efficacy for Smoking Cessation: Secondary Analysis of the EAGLES Randomized Clinical Trial. JAMA Netw Open. 2021 Jan 4;4(1):e2032053. doi: 10.1001/jamanetworkopen.2020.32053.
Evins AE, West R, Benowitz NL, Russ C, Lawrence D, McRae T, Maravic MC, Heffner JL, Anthenelli RM. Efficacy and Safety of Pharmacotherapeutic Smoking Cessation Aids in Schizophrenia Spectrum Disorders: Subgroup Analysis of EAGLES. Psychiatr Serv. 2021 Jan 1;72(1):7-15. doi: 10.1176/appi.ps.202000032. Epub 2020 Nov 3.
Ayers CR, Heffner JL, Russ C, Lawrence D, McRae T, Evins AE, Anthenelli RM. Efficacy and safety of pharmacotherapies for smoking cessation in anxiety disorders: Subgroup analysis of the randomized, active- and placebo-controlled EAGLES trial. Depress Anxiety. 2020 Mar;37(3):247-260. doi: 10.1002/da.22982. Epub 2019 Dec 18.
Heffner JL, Evins AE, Russ C, Lawrence D, Ayers CR, McRae T, Aubin LS, Krishen A, West R, Anthenelli RM. Safety and efficacy of first-line smoking cessation pharmacotherapies in bipolar disorders: Subgroup analysis of a randomized clinical trial. J Affect Disord. 2019 Sep 1;256:267-277. doi: 10.1016/j.jad.2019.06.008. Epub 2019 Jun 3.
Anthenelli RM, Gaffney M, Benowitz NL, West R, McRae T, Russ C, Lawrence D, St Aubin L, Krishen A, Evins AE. Predictors of Neuropsychiatric Adverse Events with Smoking Cessation Medications in the Randomized Controlled EAGLES Trial. J Gen Intern Med. 2019 Jun;34(6):862-870. doi: 10.1007/s11606-019-04858-2. Epub 2019 Mar 7.
West R, Evins AE, Benowitz NL, Russ C, McRae T, Lawrence D, St Aubin L, Krishen A, Maravic MC, Anthenelli RM. Factors associated with the efficacy of smoking cessation treatments and predictors of smoking abstinence in EAGLES. Addiction. 2018 Aug;113(8):1507-1516. doi: 10.1111/add.14208. Epub 2018 Mar 30.
Anthenelli RM, Benowitz NL, West R, St Aubin L, McRae T, Lawrence D, Ascher J, Russ C, Krishen A, Evins AE. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016 Jun 18;387(10037):2507-20. doi: 10.1016/S0140-6736(16)30272-0. Epub 2016 Apr 22.
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01456936