Tobacco Use Cessation
Conditions
Brief summary
The primary goal of this study is to compare efficacy of varenicline to placebo for cessation of use of smokeless tobacco.
Interventions
Subjects will be up-titrated during the first week of treatment in the following manner: 0.5 mg once daily for 3 days followed by 0.5 mg twice daily for 4 days, and then 1 mg twice daily for the following 11 weeks of the treatment period.
DRUGPlacebo
Subjects will be up-titrated during the first week of treatment in the following manner: 0.5 mg once daily for 3 days followed by 0.5 mg twice daily for 4 days, and then 1 mg twice daily for the following 11 weeks of the treatment period.
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
* Male or female daily smokeless tobacco users aged 18 years and older, who are motivated to stop use of all tobacco products. * Subjects must be daily users of nicotine containing smokeless tobacco and using smokeless tobacco on at least 8 occasions per day averaged over a week. * Have used smokeless tobacco for at least 1 year prior to screening with no period of abstinence \>3 months in the past year.
Exclusion criteria
* Subjects using nicotine containing products (including smoking tobacco) other than smokeless tobacco for 3 months prior to screening. * Subjects with exhaled Carbon Monoxide (CO) \>10 ppm at baseline. * Subjects who have used varenicline, bupropion, or NRT within 3 months of screening. * Subjects currently or within the past 12 months requiring treatment for depression or have a current or prior history of panic disorder, psychosis, bipolar disorder or any other serious mental illness.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With a 4 Week Continuous Quit Rate (CQR) From Smokeless Tobacco | Weeks 9 through 12 | Number of subjects who reported no use of nicotine-containing products by answering No to the nicotine use inventory (NUI) question: Has the subject used any nicotine-containing products in the last 7 days (Week 9) or since last study visit (Week 10 through 12) and confirmed salivary cotinine \<= 15 ng/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Continuous Abstinence (CA) of Smokeless Tobacco Use | Week 9 through 12, Week 26 | Number of subjects who remainded abstinent from the period defined as start of the primary endpoint (Week 9) through the end of follow up (Week 26) by reporting no use of nicotine-containing products and confirmed salivary cotinine \<= 15 ng/mL. |
| Number of Subjects With Long Term Quit Rate (LTQR) of Smokeless Tobacco | Week 26 | 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 using nicotine containing products from Week 12 through Week 26. |
| Number of Subjects With 7-day Point Prevalence (PP) of Abstinence at the End of Treatment (Week 12) and at the End of Study (Week 26) | Week 12, Week 26 | Number of subjects at Week 12 and Week 26 reporting no use of nicotine-containing products in the last 7 days and confirmed salivary cotinine \<= 15 ng/mL. |
Countries
Norway, Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Varenicline Tartrate Subjects will be up-titrated during the first week of treatment in the following manner: 0.5 mg once daily for 3 days followed by 0.5 mg twice daily for 4 days, and then 1 mg twice daily for the following 11 weeks of the treatment period. | 213 |
| Placebo Subjects will be up-titrated with a matching placebo during the first week of treatment in the following manner: 0.5 mg once daily for 3 days followed by 0.5 mg twice daily for 4 days, and then 1 mg twice daily for the following 11 weeks of the treatment period. | 218 |
| Total | 431 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 19 | 9 |
| Overall Study | Lack of Efficacy | 3 | 13 |
| Overall Study | Lost to Follow-up | 9 | 6 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Randomized but not treated | 1 | 0 |
| Overall Study | Withdrawal by Subject | 12 | 19 |
Baseline characteristics
| Characteristic | Varenicline Tartrate | Placebo | Total |
|---|---|---|---|
| Age, Customized 18 - 44 years | 117 participants | 115 participants | 232 participants |
| Age, Customized 45 - 64 years | 88 participants | 93 participants | 181 participants |
| Age, Customized >= 65 years | 8 participants | 10 participants | 18 participants |
| Sex: Female, Male Female | 24 Participants | 22 Participants | 46 Participants |
| Sex: Female, Male Male | 189 Participants | 196 Participants | 385 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 151 / 213 | 107 / 218 |
| serious Total, serious adverse events | 2 / 213 | 3 / 218 |
Outcome results
Primary
Number of Subjects With a 4 Week Continuous Quit Rate (CQR) From Smokeless Tobacco
Number of subjects who reported no use of nicotine-containing products by answering No to the nicotine use inventory (NUI) question: Has the subject used any nicotine-containing products in the last 7 days (Week 9) or since last study visit (Week 10 through 12) and confirmed salivary cotinine \<= 15 ng/mL.
Time frame: Weeks 9 through 12
Population: Intent to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline Tartrate | Number of Subjects With a 4 Week Continuous Quit Rate (CQR) From Smokeless Tobacco | 125 participants |
| Placebo | Number of Subjects With a 4 Week Continuous Quit Rate (CQR) From Smokeless Tobacco | 85 participants |
p-value: <0.000195% CI: [1.59, 3.58]Regression, Logistic
Secondary
Number of Subjects With 7-day Point Prevalence (PP) of Abstinence at the End of Treatment (Week 12) and at the End of Study (Week 26)
Number of subjects at Week 12 and Week 26 reporting no use of nicotine-containing products in the last 7 days and confirmed salivary cotinine \<= 15 ng/mL.
Time frame: Week 12, Week 26
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline Tartrate | Number of Subjects With 7-day Point Prevalence (PP) of Abstinence at the End of Treatment (Week 12) and at the End of Study (Week 26) | Week 12 | 123 participants |
| Varenicline Tartrate | Number of Subjects With 7-day Point Prevalence (PP) of Abstinence at the End of Treatment (Week 12) and at the End of Study (Week 26) | Week 26 | 102 participants |
| Placebo | Number of Subjects With 7-day Point Prevalence (PP) of Abstinence at the End of Treatment (Week 12) and at the End of Study (Week 26) | Week 12 | 85 participants |
| Placebo | Number of Subjects With 7-day Point Prevalence (PP) of Abstinence at the End of Treatment (Week 12) and at the End of Study (Week 26) | Week 26 | 88 participants |
Comparison: Week 12p-value: <0.000195% CI: [1.52, 3.41]Regression, Logistic
Comparison: Week 26p-value: 0.091995% CI: [0.94, 2.13]Regression, Logistic
Secondary
Number of Subjects With Continuous Abstinence (CA) of Smokeless Tobacco Use
Number of subjects who remainded abstinent from the period defined as start of the primary endpoint (Week 9) through the end of follow up (Week 26) by reporting no use of nicotine-containing products and confirmed salivary cotinine \<= 15 ng/mL.
Time frame: Week 9 through 12, Week 26
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline Tartrate | Number of Subjects With Continuous Abstinence (CA) of Smokeless Tobacco Use | Week 10 | 135 participants |
| Varenicline Tartrate | Number of Subjects With Continuous Abstinence (CA) of Smokeless Tobacco Use | Week 12 | 125 participants |
| Varenicline Tartrate | Number of Subjects With Continuous Abstinence (CA) of Smokeless Tobacco Use | Week 11 | 132 participants |
| Varenicline Tartrate | Number of Subjects With Continuous Abstinence (CA) of Smokeless Tobacco Use | Week 26 | 95 participants |
| Varenicline Tartrate | Number of Subjects With Continuous Abstinence (CA) of Smokeless Tobacco Use | Week 9 | 140 participants |
| Placebo | Number of Subjects With Continuous Abstinence (CA) of Smokeless Tobacco Use | Week 26 | 73 participants |
| Placebo | Number of Subjects With Continuous Abstinence (CA) of Smokeless Tobacco Use | Week 9 | 101 participants |
| Placebo | Number of Subjects With Continuous Abstinence (CA) of Smokeless Tobacco Use | Week 10 | 96 participants |
| Placebo | Number of Subjects With Continuous Abstinence (CA) of Smokeless Tobacco Use | Week 11 | 93 participants |
| Placebo | Number of Subjects With Continuous Abstinence (CA) of Smokeless Tobacco Use | Week 12 | 85 participants |
Comparison: Week 26p-value: 0.011895% CI: [1.12, 2.58]Regression, Logistic
Secondary
Number of Subjects With Long Term Quit Rate (LTQR) of Smokeless Tobacco
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 using nicotine containing products from Week 12 through Week 26.
Time frame: Week 26
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline Tartrate | Number of Subjects With Long Term Quit Rate (LTQR) of Smokeless Tobacco | 102 participants |
| Placebo | Number of Subjects With Long Term Quit Rate (LTQR) of Smokeless Tobacco | 78 participants |
p-value: 0.006395% CI: [1.17, 2.67]Regression, Logistic