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

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

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 Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: Placebo; Drug: varenicline tartrate; Drug: bupropion hydrochloride; Drug: Nicotine Replacement Therapy Patch

• Study Type: Interventional
• Enrollment (Actual): 8144
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autonoma de Bs. As, Buenos Aires, Argentina, C1426ABP
      • Centro Médico Dra. De Salvo
    • Mataderos, Buenos Aires, Argentina, C1440BRR
      • Centro de Investigacion Clinica WM
• Australia
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane & Women's Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Monash Alfred Psychiatry Research Centre
• Brazil
  • CE
    • Fortaleza, CE, Brazil, 60846-190
      • Hospital de Messejana Dr. Carlos Alberto Studart Gomes
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital Sao Lucas da PUCRS - Uniao Brasileira de Educacao e Assistencia
    • Porto Alegre, RS, Brazil, 90035-074
      • Irmandade da Santa Casa de Misericórdia Porto Alegre
  • SP
    • Campinas, SP, Brazil, 13059-740
      • Hospital e Maternidade Celso Pierro - Pontifícia Universidade Católica de Campinas - Campus II
    • Sao Paulo, SP, Brazil, 05017-000
      • Instituto Jaqueline Scholz Issa e Mario Issa de cardiologia S/C Ltda
• Bulgaria
  • Bourgas, Bulgaria, 8000
    • Mental Health Center "Prof. Dr. Ivan Temkov-Bourgas" Ltd.
  • Kazanlak, Bulgaria, 6100
    • MBAL Dr. Hristo Stambolski EOOD
  • Novi Iskar, Bulgaria, 1282
    • DPB Sv. Ivan Rilski
  • Pleven, Bulgaria, 5800
    • UMBAL Dr. Georgi Stranski EAD,
  • Plovdiv, Bulgaria, 4002
    • UMBAL Sveti Georgi EAD, Klinika po psihiatriya
  • Ruse, Bulgaria, 7002
    • SBALPFZ - Ruse EOOD
  • Ruse, Bulgaria, 7004
    • Tsentar za psihichno zdrave - Ruse EOOD
  • Sofia, Bulgaria, 1113
    • MHATNP Sveti Naum SJsc.
  • Sofia, Bulgaria, 1113
    • Meditsinski Tsentar ¿Sveti Naum¿ EOOD
  • Troyan, Bulgaria, 5600
    • Specializirana Bolnitsa za Aktivno Lechenie na Belodrobni Bolesti-Troyan EOOD,
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8M 1K7
      • Hamilton Medical Research Group
    • Mississauga, Ontario, Canada, L5M 4N4
      • Medical Research Associates
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
    • Toronto, Ontario, Canada, M3J 2C5
      • Canadian Phase Onward Inc.
    • Toronto, Ontario, Canada, M5S 2S1
      • Centre for Addiction and Mental Health (CAMH)
    • Toronto, Ontario, Canada, M4W 3C7
      • Dr. Felix Yaroshevsky
    • Toronto, Ontario, Canada, M6J 1H4
      • Centre of Addiction and Mental Health Pharmacy
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • Diex Research Sherbrooke Inc.
• Chile
  • Maule
    • Talca, Maule, Chile, 3460001
      • Hospital Regional de Talca, Unidad de Enfermedades Respiratorias
  • Valparaiso, V Region
    • Quillota, Valparaiso, V Region, Chile, 2260877
      • Centro Respiratorio Integral (CENRESIN Ltda.)
• Denmark
  • Ballerup, Denmark, 2750
    • CCBR A/S
  • Vejle, Denmark, 7100
    • CCBR A/S
• Finland
  • Espoo, Finland, 02600
    • Mehiläinen Leppävaara
  • Kuopio, Finland, 70110
    • Savon Psykiatripalvelu Oy
  • Nummela, Finland, 03100
    • Mehiläinen Nummela
  • Oulu, Finland, 90100
    • Oulu Mentalcare
  • Pori, Finland, 28100
    • Porin Lääkäritalo Oy
  • Turku, Finland, 20100
    • PEL, Psykiatrian ErikoiLääkärit
• Germany
  • Berlin, Germany, 10629
    • emovis GmbH
  • Berlin, Germany, 10117
    • Klinische Forschung Berlin-Mitte GmbH
  • Freiburg, Germany, 79104
    • Universitaetsklinikum Freiburg
  • Hamburg, Germany, 20253
    • Klinische Forschung Hamburg GmbH
  • Muenchen, Germany, 80336
    • Ludwig Maximilians-Universitaet Muenchen
  • Tuebingen, Germany, 72076
    • Universitaetsklinik Tuebingen
  • Sachsen
    • Leipzig, Sachsen, Germany, 04157
      • ZSL - Zentrum fuer Medizinische Studien Leipzig GmbH
• Mexico
  • D.f.
    • Mexico, D.f., Mexico, 14050
      • Centro Respiratorio de Mexico S.C.
  • Mexico DF
    • Colonia Hipodromo Condesa, Mexico DF, Mexico, 06100
      • Consultarios de Medicina Especializada del Sector Privado
  • Michoacan
    • Morelia, Michoacan, Mexico, 58249
      • Clinica de Enfermedades Cronicas y de Procedimientos Especiales S.C.
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64620
      • Centro de Estudios Clínicos y Especialidades Médicas S.C.
• New Zealand
  • Rotorua, New Zealand, 3010
    • Lakeland Clinical Trials
• Russian Federation
  • Moscow, Russian Federation, 107076
    • FSBI "Federal Medical Research Center of Psychiatry and Addiction Medicine"
  • Moscow, Russian Federation, 117152
    • Moscow State Public Healthcare Institution Mental Clinical Hospital #1 n.a. N.A. Alexeeva
  • Moscow, Russian Federation, 125367
    • Clinical Mental Hospital #12 of Moscow Healthcare Department
  • Moscow, Russian Federation, 107076
    • FSBI Moscow Scientific Research Institute of Psychiatry"
  • Nizhni Novgorod, Russian Federation, 603155
    • Clinical Psychiatric Hospital #1 of Nizhni Novgorod
  • Saint-Petersburg, Russian Federation, 192019
    • FSBI "Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev" of MoH
  • Smolensk, Russian Federation, 214019
    • SBEI HPE ##Smolensk State Medical Academy## of MoH of RF
  • Smolensk, Russian Federation, 214019
    • Smolensk State Medical Academy of Ministry of Healthcare of Russian Federation
  • St. Petersburg, Russian Federation, 190121
    • St. Petersburg State Healthcare Institution, St. Nikolay Chudotvorets Mental Hospital
  • St. Petersburg, Russian Federation, 197341
    • State Healthcare Institution "Psychoneurological Dispensary #2
• Slovakia
  • Bratislava, Slovakia, 82007
    • Psychiatricka ambulancia, Mentum, s.r.o.
  • Bratislava, Slovakia, 851 01
    • Vavrusová consulting s.r.o., Nestatna psychiatricka ambulancia, MUDr. Livia Vavrusova, PhD
  • Levice, Slovakia, 93401
    • Psychiatricka ambulancia MUDr. Nada Kuriackova, s.r.o.
  • Rimavska Sobota, Slovakia, 979 01
    • Psychiatricka ambulancia, PsychoLine s.r.o.
  • Roznava, Slovakia, 04801
    • Nemocnica s poliklinikou sv. Barbory Roznava a.s.
• South Africa
  • Cape Town
    • Bellville, Cape Town, South Africa, 7530
      • Flexivest Fourteen Research Center
  • Gauteng
    • Benoni, Johannesburg, Gauteng, South Africa, 1500
      • Worthwhile Clinical Trials
    • Centurion, Gauteng, South Africa, 0157
      • Vista Clinic
    • Johannesburg, Gauteng, South Africa, 1818
      • Soweto Clinical Trials Centre
    • Lyttelton, Gauteng, South Africa, 0157
      • I Engelbrecht Research Pty, Ltd
    • Midrand, Gauteng, South Africa, 1685
      • Midrand Medical Centre
  • Kwa-Zulu Natal
    • Durban, Kwa-Zulu Natal, South Africa, 4091
      • Private Practice
  • Kwazulu Natal
    • Durban, Kwazulu Natal, South Africa, 4091
      • Randles Road Medical Centre
  • Western Cape
    • Cape Town, Western Cape, South Africa, 8001
      • Dr John OBrien Incorporated
• Spain
  • Barcelona, Spain, 08025
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Barcelona, Spain, 08035
    • Hospital General Universitari Vall d'Hebron
  • Caceres, Spain, 10003
    • Hospital San Pedro de Alcantara
  • Madrid, Spain, 28015
    • Unidad Especializada en Tabaquismo de la Comunidad de Madrid
  • Zaragoza, Spain, 50007
    • Centro de Salud Torrero La Paz
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research, Inc.
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • NoesisPharma Research
  • California
    • Encino, California, United States, 91316
      • Pharmacology Research Institute
    • Escondido, California, United States, 92025
      • Synergy Clinical Research of Escondido
    • Imperial, California, United States, 92251
      • Sun Valley Research Center
    • La Habra, California, United States, 90631
      • Omega Clinical Trials
    • La Jolla, California, United States, 92037
      • Pacific Treatment and Research Center UC San Diego Health System
    • Los Alamitos, California, United States, 90720
      • Pharmacology Research Institute
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at University of California, Los Angeles
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
    • Oceanside, California, United States, 92056
      • North County Clinical Research
    • Orange, California, United States, 92868
      • Neuropsychiatric Research Center of Orange County
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, Inc.
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver, Anschutz Medical Campus , Behavioral Health and Wellness Program
    • Denver, Colorado, United States, 80209
      • Western Affiliated Research Institute
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Comprehensive Psychiatric Care
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Neuropsychiatric Research Center of Southwest Florida
    • Hollywood, Florida, United States, 33024
      • Broward Research Group
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions,Inc.
    • Lakeland, Florida, United States, 33805
      • Meridien Research
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
    • Ocala, Florida, United States, 34474
      • Ocala Psychiatric Associates
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc
    • Tampa, Florida, United States, 33634
      • Meridien Research
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Behavioral Research Center
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research
    • Meridian, Idaho, United States, 83642
      • Northwest Neurobehavioral Health
  • Illinois
    • Naperville, Illinois, United States, 60563
      • AMR-Baber Research Inc.
  • Indiana
    • Indianaopolis, Indiana, United States, 46254
      • American Health Network of IN, LLC
    • Indianapolis, Indiana, United States, 46260
      • Goldpoint Clinical Research, LLC
    • Indianapolis, Indiana, United States, 46250
      • Davis Clinic, Incorporated
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates, Inc.
    • Louisville, Kentucky, United States, 40218
      • Kentucky Research Group
  • Louisiana
    • Metairie, Louisiana, United States, 70002
      • A Professional Corporation dba The Center for Sexual Health
  • Maine
    • Auburn, Maine, United States, 04210
      • Maine Research Associates
    • Lewiston, Maine, United States, 04240
      • Community Clinical Services
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Milford, Massachusetts, United States, 01757
      • Milford Emergency Associates, Incorporated
    • Milford, Massachusetts, United States, 01757
      • Rahim Shafa, MD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota- TC
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research, PC
    • St.Louis, Missouri, United States, 63141
      • Mercy Health Research
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes LLC; Princeton Medical Institute Woodlands Professional Building
  • New York
    • Brooklyn, New York, United States, 11235
      • Social Psychiatry Research Institute Clinical Trials LLC
    • Endwell, New York, United States, 13760
      • Regional Clinical Research, Inc.
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • PMG Research of Raleigh, LLC d/b/a PMG Research of Cary
    • Cary, North Carolina, United States, 27511
      • Tooley Group
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Internal Medicine Consultants, Inc
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health and Sciences University
  • Pennsylvania
    • Broomall, Pennsylvania, United States, 19008
      • Southeastern PA Medical Institute
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Worldwide, LLC
    • Philadelphia, Pennsylvania, United States, 19131
      • Belmont Center For Comprehensive Treatment
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Lincoln Research
    • Lincoln, Rhode Island, United States, 02865
      • East Side Clinical Laboratory
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center for Clinical Research
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc.
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates, Inc.
    • Nashville, Tennessee, United States, 37203
      • James G. Kyser, MD
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Clinical Trials, L.P.
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research
    • Houston, Texas, United States, 77230-1439
      • The University of Texas M.D. Anderson Cancer Center
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Peninsula Psychotherapy Center, LLC
    • Norfolk, Virginia, United States, 23507
      • Clinical Research Associates of Tidewater
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Madison, Wisconsin, United States, 53711-2027
      • University of Wisconsin School of Medicine and Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Chantix; Champix
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: 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 Names: NRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Neuropsychiatric (NPS) Adverse Events (AE) - the Primary Study Endpoint	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.	Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.
Estimated NPS AE Rate (%), by Cohort	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.	Treatment emergent is first dose date to last dose date (up to 12 weeks) plus 30 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of the Components of the NPS AE Primary Endpoint, Non-psychiatric History Cohort	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.	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	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.	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)	The NPS AE composite results (as previously described) are for the two cohorts combined and are presented below.	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	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.	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	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.	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	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.	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)	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.	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	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.	Baseline to Week 24
HADS Total Score, Psychiatric History Cohort	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.	Baseline to Week 24
HADS Total Score (Overall)	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.	Baseline to Week 24
Positive Responses for Suicidal Behavior and/or Ideation by Columbia Suicide Severity Rating Scale (C-SSRS) - Non-psychiatric History Cohort	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.	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	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.	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	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.	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	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.	Baseline to Week 24
CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Non-psychiatric History Cohort	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).	Week 9 through Week 12
CO-Confirmed Continuous Abstinence for Weeks 9 Through 12, Psychiatric History Cohort	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).	Week 9 through Week 12
CO-Confirmed Continuous Abstinence for Weeks 9 Through 12 (Overall)	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).	Week 9 through Week 12
CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Non-psychiatric History Cohort	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).	Week 9 through Week 24
CO-confirmed Continuous Abstinence From Week 9 Through Week 24, Psychiatric History Cohort	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).	Week 9 through Week 24
CO-confirmed Continuous Abstinence From Week 9 Through Week 24 (Overall)	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).	Week 9 through Week 24
7-Day Point Prevalence of Abstinence, Non-psychiatric History Cohort	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?	24 Weeks
7-Day Point Prevalence of Abstinence, Psychiatric History Cohort	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?	24 Weeks
7-Day Point Prevalence of Abstinence (Overall)	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?	24 Weeks

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: GlaxoSmithKline

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): January 1, 2015
• Study Completion (ACTUAL): January 1, 2015

Study Registration Dates

• First Submitted: October 14, 2011
• First Submitted That Met QC Criteria: October 19, 2011
• First Posted (ESTIMATE): October 21, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): June 10, 2016
• Last Update Submitted That Met QC Criteria: May 9, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: smoking cessation; psychiatric disease
• Additional Relevant MeSH Terms: Behavioral Symptoms; Problem Behavior; Mental Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Cytochrome P-450 Enzyme Inhibitors; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Dopamine Uptake Inhibitors; Nicotine; Bupropion; Varenicline
• Other Study ID Numbers: A3051123; 2010-022914-15 (EUDRACT_NUMBER); EAGLES (Alias Study Number)