Smoking Cessation
Conditions
Keywords
smoking cessation, smoking cessation in COPD
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.
Interventions
DRUGplacebo
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)
DRUGVarenicline 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)
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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). |
| 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. |
Countries
France, Italy, Spain, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Varenicline 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. | 248 |
| Placebo 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. | 251 |
| Total | 499 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Assigned to Study Treatment (Tx) | Other | 2 | 3 |
| Received Study Tx | Adverse Event | 5 | 11 |
| Received Study Tx | Death | 2 | 1 |
| Received Study Tx | Lack of Efficacy | 0 | 3 |
| Received Study Tx | Lost to Follow-up | 29 | 31 |
| Received Study Tx | Other | 5 | 5 |
| Received Study Tx | Withdrawal by Subject | 31 | 43 |
Baseline characteristics
| Characteristic | Varenicline | Placebo | Total |
|---|---|---|---|
| Age Continuous | 57.2 years STANDARD_DEVIATION 9.1 | 57.1 years STANDARD_DEVIATION 9 | 57.1 years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 93 Participants | 95 Participants | 188 Participants |
| Sex: Female, Male Male | 155 Participants | 156 Participants | 311 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 157 / 248 | 121 / 251 |
| serious Total, serious adverse events | 6 / 248 | 11 / 251 |
Outcome results
Primary
Number of Subjects With Four Week Continuous Quit Rate (CQR)
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
Population: All subjects population: received at least 1 dose, including partial doses, of randomized study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Number of Subjects With Four Week Continuous Quit Rate (CQR) | 105 participants |
| Placebo | Number of Subjects With Four Week Continuous Quit Rate (CQR) | 22 participants |
Comparison: 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.p-value: <0.000195% CI: [4.99, 14.14]Regression, Logistic
Secondary
Change From Baseline in Body Weight
Change from baseline calculated as mean at observation minus baseline value; body weight measured in kilograms (kg).
Time frame: Baseline, Week 52
Population: Subjects with change in body weight in the All subjects population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Change From Baseline in Body Weight | 2.4 kg | Standard Deviation 6.3 |
| Placebo | Change From Baseline in Body Weight | 1.5 kg | Standard Deviation 4 |
Secondary
Change From Baseline in Clinical COPD Questionnaire (CCQ)
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
Population: All subjects; (n) = subjects with analyzable data at observation for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 24 Mental State (n=191, 161) | -0.72 scores on scale | Standard Deviation 1.36 |
| Varenicline | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 12 Respiratory Symptoms (n=213, 193) | -1.16 scores on scale | Standard Deviation 1.19 |
| Varenicline | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 12 Functional State (n=214, 192) | -0.41 scores on scale | Standard Deviation 0.98 |
| Varenicline | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 24 Respiratory Symptoms (n=191, 161) | -0.98 scores on scale | Standard Deviation 1.08 |
| Varenicline | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 12 Mental State (n=214, 193) | -0.81 scores on scale | Standard Deviation 1.25 |
| Varenicline | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 24 Functional State (n=191, 160) | -0.40 scores on scale | Standard Deviation 1.01 |
| Varenicline | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 12 Total Score (n=213, 192) | -0.79 scores on scale | Standard Deviation 0.91 |
| Varenicline | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 52 Mental State (n=174, 155) | -0.58 scores on scale | Standard Deviation 1.37 |
| Varenicline | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 24 Total Score (n=191, 160) | -0.70 scores on scale | Standard Deviation 0.89 |
| Varenicline | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 52 Functional State (n=175, 154) | -0.35 scores on scale | Standard Deviation 0.96 |
| Varenicline | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 52 Total Score (n=174, 154) | -0.62 scores on scale | Standard Deviation 0.89 |
| Varenicline | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 52 Respiratory Symptoms (n=175, 155) | -0.90 scores on scale | Standard Deviation 1.16 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 52 Total Score (n=174, 154) | -0.39 scores on scale | Standard Deviation 1.05 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 12 Mental State (n=214, 193) | -0.64 scores on scale | Standard Deviation 1.31 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 24 Mental State (n=191, 161) | -0.49 scores on scale | Standard Deviation 1.43 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 52 Mental State (n=174, 155) | -0.46 scores on scale | Standard Deviation 1.39 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 12 Functional State (n=214, 192) | -0.35 scores on scale | Standard Deviation 1 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 24 Functional State (n=191, 160) | -0.25 scores on scale | Standard Deviation 1.02 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 52 Functional State (n=175, 154) | -0.12 scores on scale | Standard Deviation 1.06 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 12 Respiratory Symptoms (n=213, 193) | -0.88 scores on scale | Standard Deviation 1.17 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 24 Respiratory Symptoms (n=191, 161) | -0.82 scores on scale | Standard Deviation 1.14 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 52 Respiratory Symptoms (n=175, 155) | -0.63 scores on scale | Standard Deviation 1.36 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 12 Total Score (n=213, 192) | -0.62 scores on scale | Standard Deviation 0.93 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire (CCQ) | Week 24 Total Score (n=191, 160) | -0.52 scores on scale | Standard Deviation 0.93 |
Comparison: Week 12 Mental Statep-value: 0.078ANCOVA
Comparison: Week 24 Mental Statep-value: 0.109ANCOVA
Comparison: Week 52 Mental Statep-value: 0.281ANCOVA
Comparison: Week 12 Functional Statep-value: 0.581ANCOVA
Comparison: Week 24 Functional Statep-value: 0.29ANCOVA
Comparison: Week 52 Functional Statep-value: 0.063ANCOVA
Comparison: Week 12 Respiratory Symptomsp-value: 0.002ANCOVA
Comparison: Week 24 Respiratory Symptomsp-value: 0.081ANCOVA
Comparison: Week 52 Respiratory Symptomsp-value: 0.016ANCOVA
Comparison: Week 12 Total Scorep-value: 0.033ANCOVA
Comparison: Week 24 Total Scorep-value: 0.078ANCOVA
Comparison: Week 52 Total Scorep-value: 0.023ANCOVA
Secondary
Change From Baseline in Inflammatory Biomarkers: C-Reactive Protein (CRP) and Fibrinogen Antigen
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
Population: All subjects population; (n) = number of subjects with analyzable data at observation for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in Inflammatory Biomarkers: C-Reactive Protein (CRP) and Fibrinogen Antigen | Week 12 CRP (n=210, 197) | -0.0 mg/dl | Standard Deviation 1 |
| Varenicline | Change From Baseline in Inflammatory Biomarkers: C-Reactive Protein (CRP) and Fibrinogen Antigen | Week 52 CRP (n=162, 146) | 0.0 mg/dl | Standard Deviation 0.9 |
| Varenicline | Change From Baseline in Inflammatory Biomarkers: C-Reactive Protein (CRP) and Fibrinogen Antigen | Week 12 Fibrinogen (n=183, 174) | -25.2 mg/dl | Standard Deviation 100.6 |
| Varenicline | Change From Baseline in Inflammatory Biomarkers: C-Reactive Protein (CRP) and Fibrinogen Antigen | Week 52 Fibrinogen (n=150, 130) | -8.2 mg/dl | Standard Deviation 102.1 |
| Placebo | Change From Baseline in Inflammatory Biomarkers: C-Reactive Protein (CRP) and Fibrinogen Antigen | Week 52 Fibrinogen (n=150, 130) | 14.9 mg/dl | Standard Deviation 79.2 |
| Placebo | Change From Baseline in Inflammatory Biomarkers: C-Reactive Protein (CRP) and Fibrinogen Antigen | Week 12 CRP (n=210, 197) | -0.0 mg/dl | Standard Deviation 1 |
| Placebo | Change From Baseline in Inflammatory Biomarkers: C-Reactive Protein (CRP) and Fibrinogen Antigen | Week 12 Fibrinogen (n=183, 174) | -1.4 mg/dl | Standard Deviation 86.9 |
| Placebo | Change From Baseline in Inflammatory Biomarkers: C-Reactive Protein (CRP) and Fibrinogen Antigen | Week 52 CRP (n=162, 146) | 0.1 mg/dl | Standard Deviation 0.8 |
Secondary
Change From Baseline in Pre-bronchodilator and Post-bronchodilator Forced Expiratory Volume in First Second (FEV1)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline in Pre-bronchodilator and Post-bronchodilator Forced Expiratory Volume in First Second (FEV1) | Week 12 [LOCF] Pre-bronchodilator (n= 244, 248) | 33.69 ml | Standard Deviation 281.08 |
| Varenicline | Change From Baseline in Pre-bronchodilator and Post-bronchodilator Forced Expiratory Volume in First Second (FEV1) | Week 12 [LOCF] Post-bronchodilator (n=237, 246) | 73.84 ml | Standard Deviation 287.2 |
| Varenicline | Change From Baseline in Pre-bronchodilator and Post-bronchodilator Forced Expiratory Volume in First Second (FEV1) | Week 52 [LOCF] Pre-bronchodilator (n=244, 248) | -29.59 ml | Standard Deviation 276.53 |
| Varenicline | Change From Baseline in Pre-bronchodilator and Post-bronchodilator Forced Expiratory Volume in First Second (FEV1) | Week 52 [LOCF] Post-bronchodilator (n=237, 246) | -8.10 ml | Standard Deviation 285.8 |
| Placebo | Change From Baseline in Pre-bronchodilator and Post-bronchodilator Forced Expiratory Volume in First Second (FEV1) | Week 52 [LOCF] Post-bronchodilator (n=237, 246) | -9.51 ml | Standard Deviation 277.46 |
| Placebo | Change From Baseline in Pre-bronchodilator and Post-bronchodilator Forced Expiratory Volume in First Second (FEV1) | Week 12 [LOCF] Pre-bronchodilator (n= 244, 248) | 1.77 ml | Standard Deviation 282.28 |
| Placebo | Change From Baseline in Pre-bronchodilator and Post-bronchodilator Forced Expiratory Volume in First Second (FEV1) | Week 52 [LOCF] Pre-bronchodilator (n=244, 248) | -37.90 ml | Standard Deviation 286.47 |
| Placebo | Change From Baseline in Pre-bronchodilator and Post-bronchodilator Forced Expiratory Volume in First Second (FEV1) | Week 12 [LOCF] Post-bronchodilator (n=237, 246) | 15.61 ml | Standard Deviation 223.02 |
Comparison: Varenicline vs placebo at Week 12 \[LOCF\] pre-bronchodilatorp-value: 0.14ANCOVA
Comparison: Varenicline vs placebo at Week 12 \[LOCF\] post-bronchodilatorp-value: 0.007ANCOVA
Comparison: Varenicline vs placebo at Week 52 \[LOCF\] pre-bronchodilatorp-value: 0.684ANCOVA
Comparison: Varenicline vs placebo at Week 52 \[LOCF\] post-bronchodilatorp-value: 0.901ANCOVA
Secondary
Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period
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
Population: All subjects population; (n) = number of subjects who smoked at least 1 cigarette at the given day for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 17 (n=128, 176) | 10.5 cigarettes per day | Standard Deviation 8.3 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 1 (n=226, 231) | 19.9 cigarettes per day | Standard Deviation 11 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 2 (n=232, 230) | 18.8 cigarettes per day | Standard Deviation 10.6 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 3 (n=233, 233) | 17.7 cigarettes per day | Standard Deviation 9.9 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 4 (n=230, 232) | 17.1 cigarettes per day | Standard Deviation 9.7 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 5 (n=224, 228) | 16.5 cigarettes per day | Standard Deviation 9.6 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 6 (n=222, 230) | 16.4 cigarettes per day | Standard Deviation 9.9 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 7 (n=214, 228) | 15.9 cigarettes per day | Standard Deviation 11.3 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 8 (n=176, 201) | 13.9 cigarettes per day | Standard Deviation 12 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 9 (n=168, 193) | 12.2 cigarettes per day | Standard Deviation 9.8 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 10 (155, 187) | 12.1 cigarettes per day | Standard Deviation 9.1 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 11 (n=151, 190) | 11.6 cigarettes per day | Standard Deviation 8.3 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 12 (n=145, 188) | 11.4 cigarettes per day | Standard Deviation 8.5 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 13 (n=144, 184) | 11.1 cigarettes per day | Standard Deviation 8.5 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 14 (n=134, 183) | 11.1 cigarettes per day | Standard Deviation 8.8 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 15 (n=131, 180) | 11.1 cigarettes per day | Standard Deviation 8.5 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 16 (n=132, 179) | 10.8 cigarettes per day | Standard Deviation 8.7 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 18 (n=123, 176) | 10.7 cigarettes per day | Standard Deviation 8.3 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 19 (n=120, 176) | 10.1 cigarettes per day | Standard Deviation 7.9 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 20 (n=121, 162) | 9.7 cigarettes per day | Standard Deviation 8.6 |
| Varenicline | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 21 (n=100, 132) | 9.8 cigarettes per day | Standard Deviation 8.8 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 16 (n=132, 179) | 11.9 cigarettes per day | Standard Deviation 9.2 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 11 (n=151, 190) | 12.1 cigarettes per day | Standard Deviation 9 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 1 (n=226, 231) | 18.7 cigarettes per day | Standard Deviation 9.8 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 17 (n=128, 176) | 11.9 cigarettes per day | Standard Deviation 9.3 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 2 (n=232, 230) | 18.4 cigarettes per day | Standard Deviation 9.7 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 12 (n=145, 188) | 11.9 cigarettes per day | Standard Deviation 8.9 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 3 (n=233, 233) | 17.4 cigarettes per day | Standard Deviation 9.6 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 21 (n=100, 132) | 10.4 cigarettes per day | Standard Deviation 8.2 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 4 (n=230, 232) | 17.1 cigarettes per day | Standard Deviation 9.5 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 13 (n=144, 184) | 11.9 cigarettes per day | Standard Deviation 8.9 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 5 (n=224, 228) | 16.9 cigarettes per day | Standard Deviation 9.3 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 18 (n=123, 176) | 11.9 cigarettes per day | Standard Deviation 9.3 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 6 (n=222, 230) | 16.0 cigarettes per day | Standard Deviation 9.1 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 14 (n=134, 183) | 12.9 cigarettes per day | Standard Deviation 11.6 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 7 (n=214, 228) | 15.3 cigarettes per day | Standard Deviation 9.9 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 20 (n=121, 162) | 11.3 cigarettes per day | Standard Deviation 7.9 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 8 (n=176, 201) | 13.4 cigarettes per day | Standard Deviation 9.9 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 15 (n=131, 180) | 11.5 cigarettes per day | Standard Deviation 8.7 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 9 (n=168, 193) | 12.7 cigarettes per day | Standard Deviation 9.5 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 19 (n=120, 176) | 11.6 cigarettes per day | Standard Deviation 8.7 |
| Placebo | Number of Cigarettes Smoked Daily During First 3 Weeks of the 12-Week Treatment Period | Day 10 (155, 187) | 12.6 cigarettes per day | Standard Deviation 8.9 |
Secondary
Number of Subjects With 4-Week Point Prevalence of Abstinence
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
Population: All subjects population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Number of Subjects With 4-Week Point Prevalence of Abstinence | 65 particpants |
| Placebo | Number of Subjects With 4-Week Point Prevalence of Abstinence | 33 particpants |
Comparison: Varenicline vs placebo at Week 52p-value: 0.000295% CI: [1.52, 3.95]Regression, Logistic
Secondary
Number of Subjects With 7-Day Point Prevalence of Abstinence
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
Population: All subjects population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Subjects With 7-Day Point Prevalence of Abstinence | Week 12 | 119 participants |
| Varenicline | Number of Subjects With 7-Day Point Prevalence of Abstinence | Week 24 | 74 participants |
| Varenicline | Number of Subjects With 7-Day Point Prevalence of Abstinence | Week 52 | 65 participants |
| Placebo | Number of Subjects With 7-Day Point Prevalence of Abstinence | Week 12 | 31 participants |
| Placebo | Number of Subjects With 7-Day Point Prevalence of Abstinence | Week 24 | 34 participants |
| Placebo | Number of Subjects With 7-Day Point Prevalence of Abstinence | Week 52 | 36 participants |
Comparison: Varenicline vs placebo at Week 12p-value: <0.000195% CI: [4.39, 11.11]Regression, Logistic
Comparison: Varenicline vs placebo at Week 24p-value: <0.000195% CI: [1.79, 4.54]Regression, Logistic
Comparison: Varenicline vs placebo at Week 52p-value: 0.000895% CI: [1.37, 3.48]Regression, Logistic
Secondary
Number of Subjects With Continuous Abstinence (CA)
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
Population: All subjects population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Subjects With Continuous Abstinence (CA) | Week 52 | 46 participants |
| Varenicline | Number of Subjects With Continuous Abstinence (CA) | Week 9 | 125 participants |
| Varenicline | Number of Subjects With Continuous Abstinence (CA) | Week 24 | 64 participants |
| Placebo | Number of Subjects With Continuous Abstinence (CA) | Week 9 | 28 participants |
| Placebo | Number of Subjects With Continuous Abstinence (CA) | Week 24 | 18 participants |
| Placebo | Number of Subjects With Continuous Abstinence (CA) | Week 52 | 14 participants |
Comparison: Varenicline versus (vs) placebo at Week 24p-value: <0.000195% CI: [2.75, 8.65]Regression, Logistic
Comparison: Varenicline vs placebo at Week 52p-value: <0.000195% CI: [2.13, 7.67]Regression, Logistic
Secondary
Number of Subjects With Long Term Quit Rate (LTQR)
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
Population: All subjects population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Subjects With Long Term Quit Rate (LTQR) | Week 24 | 70 participants |
| Varenicline | Number of Subjects With Long Term Quit Rate (LTQR) | Week 52 | 53 participants |
| Placebo | Number of Subjects With Long Term Quit Rate (LTQR) | Week 24 | 19 participants |
| Placebo | Number of Subjects With Long Term Quit Rate (LTQR) | Week 52 | 17 participants |
Comparison: Varenicline vs placebo at Week 24p-value: <0.000195% CI: [2.96, 9.02]Regression, Logistic
Comparison: Varenicline vs placebo at Week 52p-value: <0.000195% CI: [2.18, 7.07]Regression, Logistic