Smoking Cessation
Conditions
Brief summary
The main purpose of this study is to compare the effectiveness and safety of the re-treatment of smokers with varenicline with placebo for smoking cessation during the last 4 weeks of a 12 week course of treatment. The study will also assess whether smokers remain abstinent at Week 24 (12 weeks after the end of treatment) and Week 52 (40 weeks after the end of treatment).
Interventions
DRUGVarenicline
Varenicline 1mg twice daily
DRUGPlacebo
Matched placebo twice daily
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Smokers aged 18 years or above and wanting to stop smoking * Smokers who have smoked an average of at least 10 cigarettes per day over the last 4 weeks * Smokers who have tried before to stop smoking at least once with varenicline, and who took varenicline for at least 2 weeks * The last attempt to stop smoking must be at least 3 months before entering the study
Exclusion criteria
* Individuals who have not tolerated varenicline well previously, or who have a current or prior medical or psychiatric history that would make entry into the trial inadvisable * Individuals who have previously participated in clinical trials of varenicline * Individuals who have been participating in another smoking cessation trial within the last 3 months, or other drug trial within the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Continuous Abstinence Rate (CAR) From Week 9 Through Week 12 | Week 9 through Week 12 | The percentage of participants who, from Week 9 through Week 12, reported no smoking and no use of other nicotine-containing products since the last study visit/last contact (on the Nicotine Use Inventory) and who did not have carbon monoxide (CO)\> 10ppm at any visits during this time frame. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CAR From Week 9 Through Week 52 | Week 9 through Week 52 | The percentage of participants who, from Week 9 through Week 52, reported no smoking (Weeks 9 through 52) and no use of other nicotine-containing products (Weeks 9 through 12), or no use of other tobacco products (Weeks 13 through 52), since the last study visit/last contact (on the Nicotine Use Inventory) and who did not have CO \>10 ppm at any of these visits during this time frame. |
| CAR From Week 9 Through Week 24 | Week 9 through Week 24 | The percentage of participants who, from Week 9 through Week 24, reported no smoking (Weeks 9 through 24) and no use of other nicotine-containing products (Weeks 9 through 12), or no use of other tobacco products (Weeks 13 through 24), since the last study visit/last contact (on the Nicotine Use Inventory) and who did not have CO \>10 ppm at any of these visits during this time frame. |
| 7-day Point Prevalence (PP) of Abstinence at Weeks 12, 24, and 52 | Weeks 12, 24 and 52 | The secondary endpoint of 7-day point prevalence of smoking cessation was determined by evaluating a participant's cigarette smoking status, and other nicotine (and/or other tobacco) use, based on the last 7 days questions in the Nicotine Use Inventory. Additionally, a participant was not considered a responder if the expired CO was \>10 ppm at the time point being summarized. Participants were considered responders independently at each visit. |
Countries
Australia, Belgium, Canada, Czechia, France, Germany, United Kingdom, United States
Participant flow
Recruitment details
This was a Phase 4, randomized, double-blind, placebo-controlled, parallel group, 2-arm, multicenter study. A total of 498 participants were randomized into the study at 36 investigator sites.
Participants by arm
| Arm | Count |
|---|---|
| Varenicline Participants received 0.5 mg per day of varenicline on Days 1 to 3, 1.0 mg per day on Days 4 to 7, and 2.0 mg per day (1.0 mg twice daily, ie, 2 x 0.5 mg tablets in the morning and 2 x 0.5 mg tablets in the evening) from Weeks 1 to 12. | 249 |
| Placebo Participants received 1 tablet per day of placebo from Days 1 to 3, which was titrated up to 2 tablets per day from Days 4 to 7, and then to 4 tablets per day (2 tablets in the morning and 2 tablets in the evening) from Week 1 to Week 12. | 245 |
| Total | 494 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Did not meet entrance criteria | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 3 |
| Overall Study | Lost to Follow-up | 34 | 30 |
| Overall Study | Other | 8 | 19 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Randomized but not treated | 2 | 2 |
| Overall Study | Withdrawal by Subject | 29 | 46 |
Baseline characteristics
| Characteristic | Varenicline | Placebo | Total |
|---|---|---|---|
| Age, Customized 18-44 years | 94 number of participants | 94 number of participants | 188 number of participants |
| Age, Customized < 18 years | 0 number of participants | 0 number of participants | 0 number of participants |
| Age, Customized 45-64 years | 135 number of participants | 139 number of participants | 274 number of participants |
| Age, Customized >= 65 years | 20 number of participants | 12 number of participants | 32 number of participants |
| Sex: Female, Male Female | 125 Participants | 124 Participants | 249 Participants |
| Sex: Female, Male Male | 124 Participants | 121 Participants | 245 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 145 / 249 | 70 / 245 |
| serious Total, serious adverse events | 7 / 249 | 4 / 245 |
Outcome results
Primary
Continuous Abstinence Rate (CAR) From Week 9 Through Week 12
The percentage of participants who, from Week 9 through Week 12, reported no smoking and no use of other nicotine-containing products since the last study visit/last contact (on the Nicotine Use Inventory) and who did not have carbon monoxide (CO)\> 10ppm at any visits during this time frame.
Time frame: Week 9 through Week 12
Population: The Full Analysis Set (FAS) included all participants as the primary participant population for efficacy analyses in this study and was defined as all participants who had received ≥1 dose, including partial doses, of randomized study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Continuous Abstinence Rate (CAR) From Week 9 Through Week 12 | 45.0 Percentage of participants |
| Placebo | Continuous Abstinence Rate (CAR) From Week 9 Through Week 12 | 11.8 Percentage of participants |
Comparison: The study was conducted on a sample size to achieve at least 90% power for the treatment comparison in the primary efficacy endpoint assuming an odds ratio of 3.36 with a placebo abstinence rate of 12% and varenicline abstinence rate of 31%. The intent of the primary efficacy analysis was to evaluate the hypothesis that varenicline is superior to placebo for smoking cessation after 12 weeks of treatment.p-value: <0.000195% CI: [4.34, 11.55]Regression, Logistic
Secondary
7-day Point Prevalence (PP) of Abstinence at Weeks 12, 24, and 52
The secondary endpoint of 7-day point prevalence of smoking cessation was determined by evaluating a participant's cigarette smoking status, and other nicotine (and/or other tobacco) use, based on the last 7 days questions in the Nicotine Use Inventory. Additionally, a participant was not considered a responder if the expired CO was \>10 ppm at the time point being summarized. Participants were considered responders independently at each visit.
Time frame: Weeks 12, 24 and 52
Population: The FAS included all participants as the primary participant population for efficacy analyses in this study and was defined as all participants who had received ≥1 dose, including partial doses, of randomized study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | 7-day Point Prevalence (PP) of Abstinence at Weeks 12, 24, and 52 | Week 12 | 53.0 Percentage of participants |
| Varenicline | 7-day Point Prevalence (PP) of Abstinence at Weeks 12, 24, and 52 | Week 24 | 32.9 Percentage of participants |
| Varenicline | 7-day Point Prevalence (PP) of Abstinence at Weeks 12, 24, and 52 | Week 52 | 28.9 Percentage of participants |
| Placebo | 7-day Point Prevalence (PP) of Abstinence at Weeks 12, 24, and 52 | Week 12 | 14.7 Percentage of participants |
| Placebo | 7-day Point Prevalence (PP) of Abstinence at Weeks 12, 24, and 52 | Week 24 | 15.5 Percentage of participants |
| Placebo | 7-day Point Prevalence (PP) of Abstinence at Weeks 12, 24, and 52 | Week 52 | 12.2 Percentage of participants |
Comparison: Week 12 assessmentp-value: <0.000195% CI: [4.92, 12.51]Regression, Logistic
Comparison: Week 24 assessmentp-value: <0.000195% CI: [1.86, 4.64]Regression, Logistic
Comparison: Week 52 assessmentp-value: <0.000195% CI: [1.88, 4.97]Regression, Logistic
Secondary
CAR From Week 9 Through Week 24
The percentage of participants who, from Week 9 through Week 24, reported no smoking (Weeks 9 through 24) and no use of other nicotine-containing products (Weeks 9 through 12), or no use of other tobacco products (Weeks 13 through 24), since the last study visit/last contact (on the Nicotine Use Inventory) and who did not have CO \>10 ppm at any of these visits during this time frame.
Time frame: Week 9 through Week 24
Population: The FAS included all participants as the primary participant population for efficacy analyses in this study and was defined as all participants who had received ≥1 dose, including partial doses, of randomized study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | CAR From Week 9 Through Week 24 | 28.9 Percentage of participants |
| Placebo | CAR From Week 9 Through Week 24 | 7.8 Percentage of participants |
p-value: <0.000195% CI: [3.25, 10.44]Regression, Logistic
Secondary
CAR From Week 9 Through Week 52
The percentage of participants who, from Week 9 through Week 52, reported no smoking (Weeks 9 through 52) and no use of other nicotine-containing products (Weeks 9 through 12), or no use of other tobacco products (Weeks 13 through 52), since the last study visit/last contact (on the Nicotine Use Inventory) and who did not have CO \>10 ppm at any of these visits during this time frame.
Time frame: Week 9 through Week 52
Population: The FAS included all participants as the primary participant population for efficacy analyses in this study and was defined as all participants who had received ≥1 dose, including partial doses, of randomized study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | CAR From Week 9 Through Week 52 | 20.1 Percentage of participants |
| Placebo | CAR From Week 9 Through Week 52 | 3.3 Percentage of participants |
Comparison: The sample size was sufficient to achieve 80% power for the treatment comparison in the key secondary end point for an odds ratio of 2.55 with a placebo abstinence rate of 6% and varenicline abstinence rate of 14%. The intent of the key secondary efficacy analysis was to evaluate the hypothesis that varenicline is superior to placebo for smoking cessation from Week 9 to the end of non-treatment follow up period at Week 52.p-value: <0.000195% CI: [3.97, 20.41]Regression, Logistic