Safety And Efficacy Of 12 Weeks Of Varenicline For Smoking Cessation In Smokers With Depression

A Phase 4 12-week, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating The Safety And Efficacy Of Varenicline Tartrate (CP-526,555) 1mg BID For Smoking Cessation In Subjects With Depression

Patients with depression tend to have a higher prevalence of smoking as well as increased severity of nicotine dependence. Phase 2 and Phase 3 varenicline clinical trials that demonstrated its efficacy and tolerability have not included subjects with depression. This smoking cessation study focuses on the depressed population and will assess the efficacy and safety of varenicline.

Study Overview

• Status: Completed
• Conditions: Depression; Smoking Cessation
• Intervention / Treatment: Drug: varenicline; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 525
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • Psychiatric Clinic, Clinical Center Banja Luka
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Clinic of Psychiatry, Clinical Center University of Sarajevo
• Croatia
  • Zagreb, Croatia, 10000
    • "Poliklinika Neuron" - Croatian Institute for Brain Research
  • Zagreb, Croatia, 10000
    • Psychiatric Hospital Vrapce
• Germany
  • Freiburg, Germany, 79104
    • Universitaetsklinikum Freiburg
  • Muenchen, Germany, 80336
    • Ludwig Maximilians-Universitaet Muenchen
  • Tuebingen, Germany, 72076
    • Universitaetsklinik Tuebingen, Klinik fuer Psychiatrie und Psychotherapie
• Hungary
  • Budapest, Hungary, 1137
    • Processus Kft., Varoskapu Rendelo
  • Budapest, Hungary, 1135
    • Fovarosi Onkormanyzat Nyiro Gyula Korhaz, II. Pszichiatriai Osztaly
  • Gyula, Hungary, 5700
    • Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza, Pszichiatriai Osztaly
  • Kunszentmarton, Hungary, 5440
    • Varosi Egeszsegugyi Kozpont
  • Szekesfehervar, Hungary, 8000
    • Fejer Megyei Szent Gyorgy Korhaz, Pszichiatriai Osztaly
  • Szentes, Hungary, 6600
    • Donatella 99 Bt.
• Romania
  • Bucuresti, Romania, 041902
    • Spitalul Clinic de Psihiatrie Prof. Dr. Al. Obregia, sectia 2
  • Iasi, Romania, 700282
    • Spitalul Clinic de Psihiatrie Socola, sectia VII
  • Sector 4
    • Bucuresti, Sector 4, Romania
      • Spitalul Psihiatrie "Prof. Dr. Al. Obregia"
• Russian Federation
  • Moscow, Russian Federation, 107076
    • Federal State Institution Moscow Scientific Research Institute of Psychiatry of Roszdrav
  • Moscow, Russian Federation, 115522
    • Institution of Russian Academy of Medical Sciences Mental Health Research Center
  • Moscow, Russian Federation, 125367
    • Moscow State Healthcare Institution Clinical Mental Hospital No 12
  • St-Petersburg, Russian Federation, 190121
    • St-Petersburg State Healthcare Institution St. Nicholas Mental Hospital
• Spain
  • Barcelona, Spain, 08025
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain, 08035
    • Hospital General de La Vall D'Hebron
  • Zaragoza, Spain, 50007
    • Centro de Salud Torrero La Paz
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Centro de Salud Mental Ii "La Corredoria"
• United States
  • California
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, Inc.
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, Inc
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Behavioral Health and Wellness Program, University of Colorado Denver
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Comprehensive Psychiatric Care
  • Florida
    • Fort Walton Beach, Florida, United States, 32547
      • Emerald Coast Mood & Memory, PA
    • Jacksonville, Florida, United States, 32216
      • Clinical Neuroscience Solutions Incorporated
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions Incorporated
  • Kansas
    • Overland, Kansas, United States, 66211
      • Vince and Associates Clinical Research
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • NorthCoast Clinical Trials Inc.
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 45237
      • University of Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Worldwide LLC
  • Tennessee
    • Bartlett, Tennessee, United States, 38134
      • Clinical Trials of Memphis
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials
    • Houston, Texas, United States, 77008
      • Claghorn-Lesem Research Clinic, Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• 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 over past month, and exhaled carbon monoxide (CO) > 10 ppm at screening
• Current or past diagnosis of MDD without psychotic features, either single or recurrent, using DSM IV TR based on clinical assessment and confirmed by SCID and at least one of the following:
• On stable antidepressant treatment for MDD (stable dose for at least 2 months)
• Major depressive episode, using DSM IV TR, in the past 2 years successfully treated

Exclusion Criteria:

• Current or past diagnosis of dementia, schizophrenia, schizoaffective disorder, or other psychotic disorder, bipolar I disorder, bipolar II disorder.
• Subjects with antisocial, schizotypal, or any other personality disorder severe enough to compromise the subject's ability to comply with the study requirements..
• Current use of either bupropion or nortryptiline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo; placebo tablets matched in appearance and dosage to varenicline tablets
Experimental: varenicline	Drug: varenicline; varenicline tablets titrated to 1 mg BID during 1st week and then 1 mg BID for 11 weeks; Other Names: Champix/Chantix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Four-Week Continuous Quit Rate (CQR)	Percentage of participants who reported no use of nicotine-containing products by answering "No" to the nicotine use inventory (NUI) questions: 'Has the participant smoked cigarettes' and 'Has the participant used other nicotine-containing products' in the last 7 days (Week 9) or since last study visit (Week 9 through 12) confirmed by a measurement of an end-expiratory exhaled carbon monoxide (CO) measurement less than or equal to 10 parts per million (ppm).	Week 9 through Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Continuous Abstinence Rate (CAR)	Percentage of participants who remained abstinent from the period defined as start of the primary endpoint (Week 9) through Week 24 and the end of follow-up (Week 52) by reporting no use of nicotine-containing products confirmed by a measurement of an end-expiratory exhaled CO measurement less than or equal to 10 ppm.	Week 9 through Week 24, Week 9 through Week 52
Number of Participants With 7-day Point Prevalence (PP) of Abstinence	Number of participants reporting no use of nicotine-containing products in the last 7 days confirmed by a measurement of an end-expiratory exhaled CO measurement less than or equal to 10 ppm.	Weeks 12, 24, 52
Number of Participants With 4-Week Point Prevalence (PP) of Abstinence	Number of participants at Week 52 visit reporting no smoking and no use of other tobacco products in the last 4 weeks confirmed by a measurement of an end-expiratory exhaled CO measurement less than or equal to 10 ppm.	Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (Including Solicited Neuropsychiatric Adverse Events)	Adverse Event (AE):any untoward medical occurrence attributed to study drug in participant who received study drug.SAE:AE causing:death;initial/prolonged inpatient hospitalization;life-threatening experience(immediate risk of dying);persistent/significant disability/incapacity;congenital anomaly.Solicited AEs collected by semi-structured neuropsychiatric AEs interview inquiring about AEs:delusions,hallucinations,paranoia,psychosis,mania,panic,agitation,hostility,aggression,homicidal ideation. If participant had positive response,investigator determined if it met AE criteria.	Baseline up to Week 16
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I)	CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement from baseline is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected	Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16, 24, 32, 40, 52
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score	CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16, 24, 32, 40, 52
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score	Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Change: mean score at observation minus mean score at baseline.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score	HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. Change: mean score at observation minus mean score at baseline.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score	The BIS-11 is a self-administered 30 items questionnaire to assess measure of impulsivity. Items are scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Total score range from 30 to 120. Barratt suggested that a total score of greater than or equal to 75 could indicate an impulse-control disorder, whereas a total score in the range of 70 to 75 could indicate pathological impulsivity.	Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS)	C-SSRS assessed if participant experienced following: completed suicide (1), suicide attempt (2)(response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3)("Yes" on "preparatory acts or behavior"), suicidal ideation (4)("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").	Baseline, Week 1 up to 30 days after Week 12 (treatment-emergent [TE]), thereafter up to Week 52 (follow-up [FU])

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Anthenelli RM, Morris C, Ramey TS, Dubrava SJ, Tsilkos K, Russ C, Yunis C. Effects of varenicline on smoking cessation in adults with stably treated current or past major depression: a randomized trial. Ann Intern Med. 2013 Sep 17;159(6):390-400. doi: 10.7326/0003-4819-159-6-201309170-00005. Erratum In: Ann Intern Med. 2013 Oct 15;159(8):576.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: February 26, 2010
• First Submitted That Met QC Criteria: February 26, 2010
• First Posted (Estimate): March 2, 2010

Study Record Updates

• Last Update Posted (Estimate): April 16, 2013
• Last Update Submitted That Met QC Criteria: March 6, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: smoking; smoking cessation; smoking cessation in depressed subjects
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: A3051122