Safety And Efficacy Of 12 Weeks Of Varenicline For Smoking Cessation In Smokers With Depression - Full Text View

Purpose

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.

Condition	Intervention	Phase
Smoking Cessation Depression	Drug: varenicline Drug: placebo	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Depression Quitting Smoking Smoking

Drug Information available for: Varenicline Varenicline tartrate

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Percentage of Participants With a Four-Week Continuous Quit Rate (CQR) [ Time Frame: Week 9 through Week 12 ] [ Designated as safety issue: No ]
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).

Secondary Outcome Measures:

Percentage of Participants With Continuous Abstinence Rate (CAR) [ Time Frame: Week 9 through Week 24, Week 9 through Week 52 ] [ Designated as safety issue: No ]
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.
Number of Participants With 7-day Point Prevalence (PP) of Abstinence [ Time Frame: Weeks 12, 24, 52 ] [ Designated as safety issue: No ]
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.
Number of Participants With 4-Week Point Prevalence (PP) of Abstinence [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
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.

Other Outcome Measures:

Number of Participants With Adverse Events (Including Solicited Neuropsychiatric Adverse Events) [ Time Frame: Baseline up to Week 16 ] [ Designated as safety issue: Yes ]
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.
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16, 24, 32, 40, 52 ] [ Designated as safety issue: Yes ]
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
Number of Participants With Clinical Global Impression - Severity (CGI-S) Score [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16, 24, 32, 40, 52 ] [ Designated as safety issue: Yes ]
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
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16 ] [ Designated as safety issue: Yes ]
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.
Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16 ] [ Designated as safety issue: Yes ]
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.
Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score [ Time Frame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16 ] [ Designated as safety issue: Yes ]
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.
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline, Week 1 up to 30 days after Week 12 (treatment-emergent [TE]), thereafter up to Week 52 (follow-up [FU]) ] [ Designated as safety issue: Yes ]
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").

Enrollment:	525
Study Start Date:	March 2010
Study Completion Date:	June 2012
Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: varenicline	Drug: varenicline varenicline tablets titrated to 1 mg BID during 1st week and then 1 mg BID for 11 weeks Other Name: Champix/Chantix
Placebo Comparator: placebo placebo	Drug: placebo placebo tablets matched in appearance and dosage to varenicline tablets

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01078298

Show 41 Study Locations

Sponsors and Collaborators

Pfizer

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT01078298 History of Changes
Other Study ID Numbers:	A3051122
Study First Received:	February 26, 2010
Results First Received:	January 17, 2013
Last Updated:	March 6, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pfizer:

smoking
smoking cessation
smoking cessation in depressed subjects

Additional relevant MeSH terms:

Smoking
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Habits
Varenicline

Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 17, 2013