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Smoking Cessation in Subjects With Mild-to-moderate Chronic Obstructive Pulmonary Disease (COPD).

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00285012
Collaborator
(none)
504
Enrollment
32
Locations
2
Arms
35
Duration (Months)
15.8
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is to be conducted in subjects with mild-to-moderate COPD who are cigarette smokers with the intent of demonstrating differences in smoking cessation between varenicline and placebo.

Condition or Disease Intervention/Treatment Phase
  • Drug: placebo
  • Drug: Varenicline Tartarate
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
504 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial With 40-Week Follow-Up Evaluating The Safety And Efficacy Of Varenicline Tartrate For Smoking Cessation In Patients With Mild-To-Moderate Chronic Obstructive Pulmonary Disease
Study Start Date :
May 1, 2006
Actual Primary Completion Date :
Jul 1, 2008
Actual Study Completion Date :
Apr 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: placebo

Drug: placebo
1mg (placebo) by mouth twice daily for 12 weeks (first week is up titration schedule---0.5mg once daily for 3 days, 0.5mg twice daily for 4 days)
Experimental: varenicline

Drug: Varenicline Tartarate
1 mg by mouth twice daily for 12 weeks (first week is up titration schedule---0.5mg once daily for 3 days, 0.5mg twice daily for 4 days)
Other Names:
  • Chantix, Champix

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Subjects With Four Week Continuous Quit Rate (CQR) [Week 9 through Week 12]

      Number of subjects who reported no smoking and no use of other nicotine-containing products since the last study visit (on the Nicotine Use Inventory [NUI]) and with end-expiratory exhaled carbon monoxide (CO) measurement less than or equal to 10 parts per million (ppm) for weeks 9 through 12 (inclusive).

    Secondary Outcome Measures

    1. Number of Subjects With Continuous Abstinence (CA) [Week 9 through Week 24 and Week 52]

      Number of subjects who reported no smoking and no use of other nicotine-containing products (treatment phase = through week 12) or tobacco products (non-treatment phase = after treatment phase; follow up through week 52) at each contact (on the NUI) and with end-expiratory exhaled CO measurement less than or equal to 10 ppm from week 9 through week 24 and week 52. CO confirmed in-clinic visit.

    2. Number of Subjects With Long Term Quit Rate (LTQR) [Week 24, Week 52]

      Number of subjects who were responders for the primary endpoint (4-week CQR for Weeks 9 through 12) and who had no more than 6 cumulative days of smoking from Week 12 through the given visit (Week 24 and Week 52). CO confirmed in-clinic visit.

    3. Number of Subjects With 7-Day Point Prevalence of Abstinence [Week 12, Week 24, Week 52]

      Number of subjects at given visit (Week 12, Week 24, Week 52) or telephone contact, reported no smoking and no use of other nicotine-containing products (treatment phase) or tobacco products (non-treatment phase) in the last 7 days and with end-expiratory exhaled CO measurement less than or equal to 10 ppm. CO confirmed in-clinic visit.

    4. Number of Subjects With 4-Week Point Prevalence of Abstinence [Week 52]

      Number of subjects at Week 52 visit reporting no smoking and no use of other tobacco products in the last 4 weeks and with end-expiratory exhaled CO measurement less than or equal to 10 ppm.

    5. Change From Baseline in Pre-bronchodilator and Post-bronchodilator Forced Expiratory Volume in First Second (FEV1) [Baseline, Week 12, Week 52]

      Change from baseline in mean FEV1 (forced expiratory volume in the first second of forced exhalation) measured in millimeters (ml) as mean at observation minus baseline value. Directly after pre-bronchodilator measurement, subject inhaled albuterol or salbutamol delivered by metered-dose inhaler (MDI); post-bronchodilator lung function repeated 30 to 45 minutes following administration of albuterol or salbutamol.

    6. Change From Baseline in Clinical COPD Questionnaire (CCQ) [Baseline, Week, 12, Week 24, Week 52]

      Change from baseline: mean at observation minus baseline value. Subject-administered 10-item instrument to systematically assess COPD symptoms (items 1, 2, 5, and 6), functional states (items 7, 8, 9, and 10) and mental states (items 3 and 4); For each domain score = sum of items divided by the number of items; total score = sum of scores divided by 10; range from 0 (very good health) to 6 (extremely poor health). Assessed at each visit based on subject's experience during the week prior to visit.

    7. Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period [Day 1 through Day 21]

      Number of cigarettes smoked daily collected during the first 3 weeks of study after randomization using patient smoking diaries.

    8. Change From Baseline in Inflammatory Biomarkers: C-Reactive Protein (CRP) and Fibrinogen Antigen [Baseline, Week 12, Week 52]

      Change from baseline in CRP and Fibrinogen antigen (blood markers of inflammation) calculated as mean at observation minus baseline value; measured as milligrams per deciliter (mg/dl).

    9. Change From Baseline in Body Weight [Baseline, Week 52]

      Change from baseline calculated as mean at observation minus baseline value; body weight measured in kilograms (kg).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    35 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Subjects will be current cigarette smokers who have smoked an average of at least 10 cigarettes per day during the past year and during the month prior to the screening visit.

    • mild to moderate COPD confirmed by spirometry

    • Subjects must have a clinical diagnosis of COPD.

    Exclusion Criteria:

    • Subjects who have made a serious attempt to quit smoking in the past 3 months.

    • Subjects who have been previously randomized in a study that has included varenicline.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pfizer Investigational Site Birmingham Alabama United States 35249-2181
    2 Pfizer Investigational Site Los Angeles California United States 90095-1690
    3 Pfizer Investigational Site Los Angeles California United States 90095-6984
    4 Pfizer Investigational Site Denver Colorado United States 80206
    5 Pfizer Investigational Site Farmington Connecticut United States 06030-2810
    6 Pfizer Investigational Site Farmington Connecticut United States 06030
    7 Pfizer Investigational Site Miami Florida United States 33143
    8 Pfizer Investigational Site Lexington Kentucky United States 40509
    9 Pfizer Investigational Site Portland Maine United States 04102
    10 Pfizer Investigational Site North Dartmouth Massachusetts United States 02747
    11 Pfizer Investigational Site Rochester Minnesota United States 55905
    12 Pfizer Investigational Site Omaha Nebraska United States 68198-5885
    13 Pfizer Investigational Site Rochester New York United States 14609
    14 Pfizer Investigational Site Chapel Hill North Carolina United States 27517
    15 Pfizer Investigational Site Chapel Hill North Carolina United States 27599-7020
    16 Pfizer Investigational Site Raleigh North Carolina United States 27607
    17 Pfizer Investigational Site Winston-Salem North Carolina United States 27103
    18 Pfizer Investigational Site Winston-Salem North Carolina United States 27157
    19 Pfizer Investigational Site Portland Oregon United States 97239-3098
    20 Pfizer Investigational Site Philadelphia Pennsylvania United States 19107
    21 Pfizer Investigational Site Nashville Tennessee United States 37203
    22 Pfizer Investigational Site Houston Texas United States 77030-1608
    23 Pfizer Investigational Site Brest France 29609
    24 Pfizer Investigational Site Montpellier Cedex 5 France 34295
    25 Pfizer Investigational Site Nice France 06000
    26 Pfizer Investigational Site Paris cedex 14 France 75679
    27 Pfizer Investigational Site Modena Italy 41100
    28 Pfizer Investigational Site Pisa Italy 56124
    29 Pfizer Investigational Site Vittorio Veneto, TV Italy 31029
    30 Pfizer Investigational Site L'hospitalet Del Llobregat Barcelona Spain 08907
    31 Pfizer Investigational Site Caceres Spain 10003
    32 Pfizer Investigational Site Madrid Spain 28015

    Sponsors and Collaborators

    • Pfizer

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00285012
    Other Study ID Numbers:
    • A3051054
    First Posted:
    Feb 1, 2006
    Last Update Posted:
    Apr 20, 2010
    Last Verified:
    Apr 1, 2010
    Keywords provided by , ,
    smoking cessation
    smoking cessation in COPD
    Additional relevant MeSH terms:
    Lung Diseases, Obstructive
    Pulmonary Disease, Chronic Obstructive
    Varenicline

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Subjects were current cigarette smokers 35 years of age or older with mild to moderate Chronic Obstructive Pulmonary Disease (COPD) as defined by Global Initiative for Chronic Obstructive Lung Diseases (GOLD) criteria.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks.
    Period Title: Assigned to Study Treatment (Tx)
    STARTED 250 254
    COMPLETED 248 251
    NOT COMPLETED 2 3
    Period Title: Assigned to Study Treatment (Tx)
    STARTED 248 251
    Completed Tx (May Continue in Study) 207 193
    Discontinued Tx (May Continue in Study) 41 58
    COMPLETED 176 157
    NOT COMPLETED 72 94

    Baseline Characteristics

    Arm/Group Title Varenicline Placebo Total
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Total of all reporting groups
    Overall Participants 248 251 499
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    57.2
    (9.1)
    57.1
    (9.0)
    57.1
    (9.1)
    Sex: Female, Male (Count of Participants)
    Female
    93
    37.5%
    95
    37.8%
    188
    37.7%
    Male
    155
    62.5%
    156
    62.2%
    311
    62.3%

    Outcome Measures

    1. Primary Outcome
    Title Number of Subjects With Four Week Continuous Quit Rate (CQR)
    Description Number of subjects who reported no smoking and no use of other nicotine-containing products since the last study visit (on the Nicotine Use Inventory [NUI]) and with end-expiratory exhaled carbon monoxide (CO) measurement less than or equal to 10 parts per million (ppm) for weeks 9 through 12 (inclusive).
    Time Frame Week 9 through Week 12

    Outcome Measure Data

    Analysis Population Description
    All subjects population: received at least 1 dose, including partial doses, of randomized study drug.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks.
    Measure Participants 248 251
    Number [participants]
    105
    42.3%
    22
    8.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Primary endpoint was based on a CO confirmed 4-week CQR (weeks 4 through 12 inclusive). Intent was to evaluate the alternative hypothesis that varenicline is superior to placebo for smoking cessation after 12 weeks of treatment in subjects with mild to moderate COPD.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value obtained from a logistic regression model including the main effects of treatment and pooled center
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 8.40
    Confidence Interval () 95%
    4.99 to 14.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments odds ratio obtained from a logistic regression model including the main effects of treatment and pooled center
    2. Secondary Outcome
    Title Number of Subjects With Continuous Abstinence (CA)
    Description Number of subjects who reported no smoking and no use of other nicotine-containing products (treatment phase = through week 12) or tobacco products (non-treatment phase = after treatment phase; follow up through week 52) at each contact (on the NUI) and with end-expiratory exhaled CO measurement less than or equal to 10 ppm from week 9 through week 24 and week 52. CO confirmed in-clinic visit.
    Time Frame Week 9 through Week 24 and Week 52

    Outcome Measure Data

    Analysis Population Description
    All subjects population
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks.
    Measure Participants 248 251
    Week 9
    125
    50.4%
    28
    11.2%
    Week 24
    64
    25.8%
    18
    7.2%
    Week 52
    46
    18.5%
    14
    5.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Varenicline versus (vs) placebo at Week 24
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value obtained from a logistic regression model including the main effects of treatment and pooled center
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.88
    Confidence Interval () 95%
    2.75 to 8.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments odds ratio obtained from a logistic regression model including the main effects of treatment and pooled center
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Varenicline vs placebo at Week 52
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value obtained from a logistic regression model including the main effects of treatment and pooled center
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.04
    Confidence Interval () 95%
    2.13 to 7.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments odds ratio obtained from a logistic regression model including the main effects of treatment and pooled center
    3. Secondary Outcome
    Title Number of Subjects With Long Term Quit Rate (LTQR)
    Description Number of subjects who were responders for the primary endpoint (4-week CQR for Weeks 9 through 12) and who had no more than 6 cumulative days of smoking from Week 12 through the given visit (Week 24 and Week 52). CO confirmed in-clinic visit.
    Time Frame Week 24, Week 52

    Outcome Measure Data

    Analysis Population Description
    All subjects population
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks.
    Measure Participants 248 251
    Week 24
    70
    28.2%
    19
    7.6%
    Week 52
    53
    21.4%
    17
    6.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Varenicline vs placebo at Week 24
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value obtained from a logistic regression model including the main effects of treatment and pooled center
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.17
    Confidence Interval () 95%
    2.96 to 9.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments odds ratio obtained from a logistic regression model including the main effects of treatment and pooled center
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Varenicline vs placebo at Week 52
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value obtained from a logistic regression model including the main effects of treatment and pooled center
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.92
    Confidence Interval () 95%
    2.18 to 7.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments odds ratio obtained from a logistic regression model including the main effects of treatment and pooled center
    4. Secondary Outcome
    Title Number of Subjects With 7-Day Point Prevalence of Abstinence
    Description Number of subjects at given visit (Week 12, Week 24, Week 52) or telephone contact, reported no smoking and no use of other nicotine-containing products (treatment phase) or tobacco products (non-treatment phase) in the last 7 days and with end-expiratory exhaled CO measurement less than or equal to 10 ppm. CO confirmed in-clinic visit.
    Time Frame Week 12, Week 24, Week 52

    Outcome Measure Data

    Analysis Population Description
    All subjects population
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks.
    Measure Participants 248 251
    Week 12
    119
    48%
    31
    12.4%
    Week 24
    74
    29.8%
    34
    13.5%
    Week 52
    65
    26.2%
    36
    14.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Varenicline vs placebo at Week 12
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value obtained from a logistic regression model including the main effects of treatment and pooled center
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 6.99
    Confidence Interval () 95%
    4.39 to 11.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments odds ratio obtained from a logistic regression model including the main effects of treatment and pooled center
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Varenicline vs placebo at Week 24
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments p-value obtained from a logistic regression model including the main effects of treatment and pooled center
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.85
    Confidence Interval () 95%
    1.79 to 4.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments odds ratio obtained from a logistic regression model including the main effects of treatment and pooled center
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Varenicline vs placebo at Week 52
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0008
    Comments p-value obtained from a logistic regression model including the main effects of treatment and pooled center
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.19
    Confidence Interval () 95%
    1.37 to 3.48
    Parameter Dispersion Type:
    Value:
    Estimation Comments odds ratio obtained from a logistic regression model including the main effects of treatment and pooled center
    5. Secondary Outcome
    Title Number of Subjects With 4-Week Point Prevalence of Abstinence
    Description Number of subjects at Week 52 visit reporting no smoking and no use of other tobacco products in the last 4 weeks and with end-expiratory exhaled CO measurement less than or equal to 10 ppm.
    Time Frame Week 52

    Outcome Measure Data

    Analysis Population Description
    All subjects population
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks.
    Measure Participants 248 251
    Number [particpants]
    65
    33
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Varenicline vs placebo at Week 52
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments p-value obtained from a logistic regression model including the main effects of treatment and pooled center
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.45
    Confidence Interval () 95%
    1.52 to 3.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments odds ratio obtained from a logistic regression model including the main effects of treatment and pooled center
    6. Secondary Outcome
    Title Change From Baseline in Pre-bronchodilator and Post-bronchodilator Forced Expiratory Volume in First Second (FEV1)
    Description Change from baseline in mean FEV1 (forced expiratory volume in the first second of forced exhalation) measured in millimeters (ml) as mean at observation minus baseline value. Directly after pre-bronchodilator measurement, subject inhaled albuterol or salbutamol delivered by metered-dose inhaler (MDI); post-bronchodilator lung function repeated 30 to 45 minutes following administration of albuterol or salbutamol.
    Time Frame Baseline, Week 12, Week 52

    Outcome Measure Data

    Analysis Population Description
    All subjects population; (n) = subjects with analyzable data at observation for varenicline and placebo, respectively. Missing data imputed by carrying the last observation forward (LOCF), including baseline values.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks.
    Measure Participants 248 251
    Week 12 [LOCF] Pre-bronchodilator (n= 244, 248)
    33.69
    (281.08)
    1.77
    (282.28)
    Week 12 [LOCF] Post-bronchodilator (n=237, 246)
    73.84
    (287.20)
    15.61
    (223.02)
    Week 52 [LOCF] Pre-bronchodilator (n=244, 248)
    -29.59
    (276.53)
    -37.90
    (286.47)
    Week 52 [LOCF] Post-bronchodilator (n=237, 246)
    -8.10
    (285.80)
    -9.51
    (277.46)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Varenicline vs placebo at Week 12 [LOCF] pre-bronchodilator
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.140
    Comments
    Method ANCOVA
    Comments p-value based on ANCOVA model with treatment and center as factors and baseline value as covariate.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Varenicline vs placebo at Week 12 [LOCF] post-bronchodilator
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.007
    Comments
    Method ANCOVA
    Comments p-value based on ANCOVA model with treatment and center as factors and baseline value as covariate.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Varenicline vs placebo at Week 52 [LOCF] pre-bronchodilator
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.684
    Comments
    Method ANCOVA
    Comments p-value based on ANCOVA model with treatment and center as factors and baseline value as covariate.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Varenicline vs placebo at Week 52 [LOCF] post-bronchodilator
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.901
    Comments
    Method ANCOVA
    Comments p-value based on ANCOVA model with treatment and center as factors and baseline value as covariate.
    7. Secondary Outcome
    Title Change From Baseline in Clinical COPD Questionnaire (CCQ)
    Description Change from baseline: mean at observation minus baseline value. Subject-administered 10-item instrument to systematically assess COPD symptoms (items 1, 2, 5, and 6), functional states (items 7, 8, 9, and 10) and mental states (items 3 and 4); For each domain score = sum of items divided by the number of items; total score = sum of scores divided by 10; range from 0 (very good health) to 6 (extremely poor health). Assessed at each visit based on subject's experience during the week prior to visit.
    Time Frame Baseline, Week, 12, Week 24, Week 52

    Outcome Measure Data

    Analysis Population Description
    All subjects; (n) = subjects with analyzable data at observation for varenicline and placebo, respectively.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks.
    Measure Participants 248 251
    Week 12 Mental State (n=214, 193)
    -0.81
    (1.25)
    -0.64
    (1.31)
    Week 24 Mental State (n=191, 161)
    -0.72
    (1.36)
    -0.49
    (1.43)
    Week 52 Mental State (n=174, 155)
    -0.58
    (1.37)
    -0.46
    (1.39)
    Week 12 Functional State (n=214, 192)
    -0.41
    (0.98)
    -0.35
    (1.00)
    Week 24 Functional State (n=191, 160)
    -0.40
    (1.01)
    -0.25
    (1.02)
    Week 52 Functional State (n=175, 154)
    -0.35
    (0.96)
    -0.12
    (1.06)
    Week 12 Respiratory Symptoms (n=213, 193)
    -1.16
    (1.19)
    -0.88
    (1.17)
    Week 24 Respiratory Symptoms (n=191, 161)
    -0.98
    (1.08)
    -0.82
    (1.14)
    Week 52 Respiratory Symptoms (n=175, 155)
    -0.90
    (1.16)
    -0.63
    (1.36)
    Week 12 Total Score (n=213, 192)
    -0.79
    (0.91)
    -0.62
    (0.93)
    Week 24 Total Score (n=191, 160)
    -0.70
    (0.89)
    -0.52
    (0.93)
    Week 52 Total Score (n=174, 154)
    -0.62
    (0.89)
    -0.39
    (1.05)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Week 12 Mental State
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.078
    Comments
    Method ANCOVA
    Comments p-value obtained from ANCOVA model with fixed effect terms for center and treatment, and baseline score as a covariate.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Week 24 Mental State
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.109
    Comments
    Method ANCOVA
    Comments p-value obtained from ANCOVA model with fixed effect terms for center and treatment, and baseline score as a covariate.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Week 52 Mental State
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.281
    Comments
    Method ANCOVA
    Comments p-value obtained from ANCOVA model with fixed effect terms for center and treatment, and baseline score as a covariate.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Week 12 Functional State
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.581
    Comments
    Method ANCOVA
    Comments p-value obtained from ANCOVA model with fixed effect terms for center and treatment, and baseline score as a covariate.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Week 24 Functional State
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.290
    Comments
    Method ANCOVA
    Comments p-value obtained from ANCOVA model with fixed effect terms for center and treatment, and baseline score as a covariate.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Week 52 Functional State
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.063
    Comments
    Method ANCOVA
    Comments p-value obtained from ANCOVA model with fixed effect terms for center and treatment, and baseline score as a covariate.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Week 12 Respiratory Symptoms
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method ANCOVA
    Comments p-value obtained from ANCOVA model with fixed effect terms for center and treatment, and baseline score as a covariate.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Week 24 Respiratory Symptoms
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.081
    Comments
    Method ANCOVA
    Comments p-value obtained from ANCOVA model with fixed effect terms for center and treatment, and baseline score as a covariate.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Week 52 Respiratory Symptoms
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.016
    Comments
    Method ANCOVA
    Comments p-value obtained from ANCOVA model with fixed effect terms for center and treatment, and baseline score as a covariate.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Week 12 Total Score
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.033
    Comments
    Method ANCOVA
    Comments p-value obtained from ANCOVA model with fixed effect terms for center and treatment, and baseline score as a covariate.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Week 24 Total Score
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.078
    Comments
    Method ANCOVA
    Comments p-value obtained from ANCOVA model with fixed effect terms for center and treatment, and baseline score as a covariate.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Week 52 Total Score
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.023
    Comments
    Method ANCOVA
    Comments p-value obtained from ANCOVA model with fixed effect terms for center and treatment, and baseline score as a covariate.
    8. Secondary Outcome
    Title Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period
    Description Number of cigarettes smoked daily collected during the first 3 weeks of study after randomization using patient smoking diaries.
    Time Frame Day 1 through Day 21

    Outcome Measure Data

    Analysis Population Description
    All subjects population; (n) = number of subjects who smoked at least 1 cigarette at the given day for varenicline and placebo, respectively.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks.
    Measure Participants 248 251
    Day 1 (n=226, 231)
    19.9
    (11.0)
    18.7
    (9.8)
    Day 2 (n=232, 230)
    18.8
    (10.6)
    18.4
    (9.7)
    Day 3 (n=233, 233)
    17.7
    (9.9)
    17.4
    (9.6)
    Day 4 (n=230, 232)
    17.1
    (9.7)
    17.1
    (9.5)
    Day 5 (n=224, 228)
    16.5
    (9.6)
    16.9
    (9.3)
    Day 6 (n=222, 230)
    16.4
    (9.9)
    16.0
    (9.1)
    Day 7 (n=214, 228)
    15.9
    (11.3)
    15.3
    (9.9)
    Day 8 (n=176, 201)
    13.9
    (12.0)
    13.4
    (9.9)
    Day 9 (n=168, 193)
    12.2
    (9.8)
    12.7
    (9.5)
    Day 10 (155, 187)
    12.1
    (9.1)
    12.6
    (8.9)
    Day 11 (n=151, 190)
    11.6
    (8.3)
    12.1
    (9.0)
    Day 12 (n=145, 188)
    11.4
    (8.5)
    11.9
    (8.9)
    Day 13 (n=144, 184)
    11.1
    (8.5)
    11.9
    (8.9)
    Day 14 (n=134, 183)
    11.1
    (8.8)
    12.9
    (11.6)
    Day 15 (n=131, 180)
    11.1
    (8.5)
    11.5
    (8.7)
    Day 16 (n=132, 179)
    10.8
    (8.7)
    11.9
    (9.2)
    Day 17 (n=128, 176)
    10.5
    (8.3)
    11.9
    (9.3)
    Day 18 (n=123, 176)
    10.7
    (8.3)
    11.9
    (9.3)
    Day 19 (n=120, 176)
    10.1
    (7.9)
    11.6
    (8.7)
    Day 20 (n=121, 162)
    9.7
    (8.6)
    11.3
    (7.9)
    Day 21 (n=100, 132)
    9.8
    (8.8)
    10.4
    (8.2)
    9. Secondary Outcome
    Title Change From Baseline in Inflammatory Biomarkers: C-Reactive Protein (CRP) and Fibrinogen Antigen
    Description Change from baseline in CRP and Fibrinogen antigen (blood markers of inflammation) calculated as mean at observation minus baseline value; measured as milligrams per deciliter (mg/dl).
    Time Frame Baseline, Week 12, Week 52

    Outcome Measure Data

    Analysis Population Description
    All subjects population; (n) = number of subjects with analyzable data at observation for varenicline and placebo, respectively.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks.
    Measure Participants 248 251
    Week 12 CRP (n=210, 197)
    -0.0
    (1.0)
    -0.0
    (1.0)
    Week 52 CRP (n=162, 146)
    0.0
    (0.9)
    0.1
    (0.8)
    Week 12 Fibrinogen (n=183, 174)
    -25.2
    (100.6)
    -1.4
    (86.9)
    Week 52 Fibrinogen (n=150, 130)
    -8.2
    (102.1)
    14.9
    (79.2)
    10. Secondary Outcome
    Title Change From Baseline in Body Weight
    Description Change from baseline calculated as mean at observation minus baseline value; body weight measured in kilograms (kg).
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    Subjects with change in body weight in the All subjects population
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks.
    Measure Participants 217 205
    Mean (Standard Deviation) [kg]
    2.4
    (6.3)
    1.5
    (4.0)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks. Placebo 0.5 milligrams (mg) once daily (QD) for 3 days; followed by 0.5 mg twice daily (BID) for 4 days; then 1 mg BID for 11 weeks.
    All Cause Mortality
    Varenicline Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Varenicline Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/248 (2.4%) 11/251 (4.4%)
    Cardiac disorders
    Acute myocardial infarction 1/248 (0.4%) 1/251 (0.4%)
    Angina pectoris 1/248 (0.4%) 0/251 (0%)
    General disorders
    Chest pain 0/248 (0%) 1/251 (0.4%)
    Hepatobiliary disorders
    Cholelithiasis 0/248 (0%) 1/251 (0.4%)
    Infections and infestations
    Appendicitis 0/248 (0%) 1/251 (0.4%)
    Bronchitis 0/248 (0%) 1/251 (0.4%)
    Cellulitis 1/248 (0.4%) 0/251 (0%)
    Pneumonia 0/248 (0%) 1/251 (0.4%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/248 (0.4%) 0/251 (0%)
    Musculoskeletal pain 0/248 (0%) 1/251 (0.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung neoplasm malignant 0/248 (0%) 2/251 (0.8%)
    Nervous system disorders
    Cerebrovascular accident 1/248 (0.4%) 0/251 (0%)
    Ischaemic stroke 0/248 (0%) 1/251 (0.4%)
    Psychiatric disorders
    Anxiety 0/248 (0%) 1/251 (0.4%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/248 (0%) 1/251 (0.4%)
    Skin and subcutaneous tissue disorders
    Hyperkeratosis 1/248 (0.4%) 0/251 (0%)
    Other (Not Including Serious) Adverse Events
    Varenicline Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 157/248 (63.3%) 121/251 (48.2%)
    Gastrointestinal disorders
    Abdominal pain 7/248 (2.8%) 2/251 (0.8%)
    Abdominal pain upper 6/248 (2.4%) 0/251 (0%)
    Constipation 12/248 (4.8%) 6/251 (2.4%)
    Diarrhoea 7/248 (2.8%) 9/251 (3.6%)
    Dry mouth 12/248 (4.8%) 4/251 (1.6%)
    Dyspepsia 9/248 (3.6%) 1/251 (0.4%)
    Flatulence 18/248 (7.3%) 13/251 (5.2%)
    Gastrooesophageal reflux disease 7/248 (2.8%) 5/251 (2%)
    Nausea 67/248 (27%) 20/251 (8%)
    Vomiting 16/248 (6.5%) 6/251 (2.4%)
    General disorders
    Fatigue 11/248 (4.4%) 1/251 (0.4%)
    Irritability 6/248 (2.4%) 4/251 (1.6%)
    Infections and infestations
    Bronchitis 9/248 (3.6%) 11/251 (4.4%)
    Influenza 5/248 (2%) 3/251 (1.2%)
    Nasopharyngitis 10/248 (4%) 11/251 (4.4%)
    Rhinitis 6/248 (2.4%) 3/251 (1.2%)
    Sinusitis 6/248 (2.4%) 5/251 (2%)
    Upper respiratory tract infection 22/248 (8.9%) 20/251 (8%)
    Investigations
    Weight increased 11/248 (4.4%) 2/251 (0.8%)
    Metabolism and nutrition disorders
    Decreased appetite 5/248 (2%) 0/251 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/248 (1.2%) 5/251 (2%)
    Back pain 6/248 (2.4%) 5/251 (2%)
    Pain in extremity 2/248 (0.8%) 5/251 (2%)
    Nervous system disorders
    Dizziness 4/248 (1.6%) 7/251 (2.8%)
    Dysgeusia 7/248 (2.8%) 6/251 (2.4%)
    Headache 20/248 (8.1%) 20/251 (8%)
    Psychiatric disorders
    Abnormal dreams 27/248 (10.9%) 7/251 (2.8%)
    Anxiety 5/248 (2%) 5/251 (2%)
    Depression 5/248 (2%) 3/251 (1.2%)
    Insomnia 24/248 (9.7%) 15/251 (6%)
    Nightmare 5/248 (2%) 1/251 (0.4%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 7/248 (2.8%) 3/251 (1.2%)
    Cough 8/248 (3.2%) 7/251 (2.8%)
    Nasal congestion 5/248 (2%) 2/251 (0.8%)
    Oropharyngeal pain 5/248 (2%) 2/251 (0.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.govCallCenter@pfizer.com
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00285012
    Other Study ID Numbers:
    • A3051054
    First Posted:
    Feb 1, 2006
    Last Update Posted:
    Apr 20, 2010
    Last Verified:
    Apr 1, 2010