Smoking
Conditions
Keywords
smoking, tobacco dependence, nicotine dependence
Brief summary
The purpose of this study is to determine if varenicline is effective in treating tobacco dependence in adults who smoke 5-10 cigarettes per day.
Detailed description
Nearly 50% of U.S. cigarette smokers smoke ≤ 10 cigarettes per day (CPD) and are considered light smokers. Most light smokers will either maintain a chronic light smoking habit or increase their level of smoking during their lifetime. Importantly, light smokers are at risk for adverse health consequences and increased all-cause mortality. While multiple factors such as reinforcement behavior, diminished autonomy, economic constraints and tobacco control policies influence light smoking, nicotine dependence appears particularly important in 5 to 10 CPD smokers. Despite the high prevalence of light smoking and its increased healthcare burden, few studies have evaluated the efficacy of pharmacotherapy for this group of smokers. Varenicline, which targets symptoms of nicotine dependence, has been shown to increase smoking abstinence rates in moderate to heavy smokers (≥ 10 cigarettes per day). However, varenicline has not been evaluated in subjects who smoke \< 10 CPD. In the current proposal we will investigate the efficacy of varenicline for smoking cessation in 5 to 10 CPD light smokers who wish to quit. This study will be conducted as a double-blind, placebo-controlled, randomized clinical trial at the Mayo Clinic, enrolling 224 eligible participants who smoke 5 to 10 CPD. Participants will receive behavior therapy and either varenicline or placebo for 12 weeks with follow up through 26 weeks. We will determine if varenicline increases smoking abstinence in light smokers at end-of-treatment and 26 weeks as compared to placebo.
Interventions
DRUGVarenicline
1 mg of varenicline twice per day for 12 weeks and brief behavioral counseling
DRUGPlacebo
1 placebo tablet twice per day for 12 weeks and brief behavioral counseling
Sponsors
Pfizer
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Subjects must be ≥ 18 years of age; 2. smokes 5 to 10 CPD for at least 6 months; 3. express interest in quitting smoking; 4. indicate ability to complete all study visits; and 5. provide written informed consent to participate in the study. 6. Subject is a female subject of non-childbearing potential or a female subject of childbearing potential - who is using contraceptives and has a negative pregnancy test result; 7. Subject is in good health as determined by the investigator; 8. Subject has the ability to participate fully in all aspects of the study and keep scheduled appointments.
Exclusion criteria
1. An active medical condition such as unstable angina, myocardial infarction, or coronary angioplasty within the past 3 months or an untreated cardiac dysrhythmia; 2. History of renal failure; 3. Cancer \[excluding non-melanoma skin cancer\] not in remission; 4. Psychosis or bipolar disorder; 5. Current unstable or untreated moderate or severe depression as assessed by the CES-D; 6. have, as defined by the C-SSRS (Columbia-Suicide Severity Rating Scale), current non-specific suicidal thoughts, or have a lifetime history of a suicidal attempt (defined as potentially self-injurious act committed with at least some wish to die, as a result of act.); 7. Substance dependence other than nicotine, defined as: a. Patient has a recent history (past month) of heavy alcohol consumption as defined by NIAAA: i. Men: More than 4 drinks on any day or 14 per week ii. Women: More than 3 drinks on any day or 7 per week. b. Use of cocaine, heroin, club drugs (i.e., MDMA/ecstasy), methamphetamine, or hallucinogens (e.g., LSD) at any time during the past month. c. Use of marijuana on a weekly basis for the past month 8. An allergy to varenicline; 9. Current use of a behavioral or pharmacologic tobacco dependence treatment and unwilling or unable to discontinue use; 10. Another member of their household already participating in this study; and 11. Current treatment with another investigational drug (within 30 days of study entry). 12. Has an unstable medical condition; 13. Subject has untreated hypertension or baseline systolic blood pressure \> 180 or diastolic \> 100; 14. Women of child-bearing potential, or who are pregnant, lactating or likely to become pregnant during the trial and are unwilling to use an acceptable form of contraception during the medication phase will also be excluded. All female subjects of childbearing potential must have a negative pregnancy test and must agree to use approved contraception during participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Point Prevalence Smoking Outcome at 12 Weeks (End of Treatment) | 12 weeks | To determine the efficacy of 12 weeks of varenicline therapy in achieving increased smoking abstinence rates in light smokers. Point prevalence is defined as no smoking in the past 7 days. |
| Prolonged Smoking Outcome at 12 Weeks (End of Treatment) | 12 weeks | To determine the efficacy of 12 weeks of varenicline therapy in achieving increased smoking abstinence rates in light smokers. Prolonged abstinence is defined as no smoking since 2 weeks after the target quit date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Point Prevalence Smoking Outcome at 24 Weeks (End of Study) | 24 weeks | To determine the efficacy of 12 weeks of varenicline therapy in achieving increased smoking abstinence rates at 6 months in light smokers. Point prevalence is defined as no smoking in the past 7 days. |
| Prolonged Smoking Outcome at 24 Weeks (End of Study) | 24 weeks | To determine the efficacy of 12 weeks of varenicline therapy in achieving increased smoking abstinence rates at 6 months in light smokers. Prolonged abstinence is defined as no smoking since 2 weeks after the target quit date. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Varenicline 1 mg of varenicline twice per day for 12 weeks.
Varenicline: 1 mg of varenicline twice per day for 12 weeks and brief behavioral counseling | 45 |
| Placebo 1 placebo tablet twice a day for 12 weeks
Placebo: 1 placebo tablet twice per day for 12 weeks and brief behavioral counseling | 48 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lack of Efficacy | 1 | 2 |
| Overall Study | Lost to Follow-up | 9 | 11 |
| Overall Study | Withdrawal by Subject | 9 | 14 |
Baseline characteristics
| Characteristic | Varenicline | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 47 Participants | 92 Participants |
| Age, Continuous | 37.1 years STANDARD_DEVIATION 11.7 | 37.2 years STANDARD_DEVIATION 11.3 | 37.2 years STANDARD_DEVIATION 11.4 |
| Baseline smoking rate (cigarettes per day) | 7.9 cigarettes per day STANDARD_DEVIATION 1.5 | 7.5 cigarettes per day STANDARD_DEVIATION 1.5 | 7.7 cigarettes per day STANDARD_DEVIATION 1.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 45 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 36 Participants | 48 Participants | 84 Participants |
| Region of Enrollment United States | 45 participants | 48 participants | 93 participants |
| Sex: Female, Male Female | 22 Participants | 34 Participants | 56 Participants |
| Sex: Female, Male Male | 23 Participants | 14 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 45 | 4 / 48 |
| serious Total, serious adverse events | 0 / 45 | 0 / 48 |
Outcome results
Primary
Point Prevalence Smoking Outcome at 12 Weeks (End of Treatment)
To determine the efficacy of 12 weeks of varenicline therapy in achieving increased smoking abstinence rates in light smokers. Point prevalence is defined as no smoking in the past 7 days.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Point Prevalence Smoking Outcome at 12 Weeks (End of Treatment) | 24 participants |
| Placebo | Point Prevalence Smoking Outcome at 12 Weeks (End of Treatment) | 7 participants |
p-value: <0.00195% CI: [2.5, 18.1]Regression, Logistic
Primary
Prolonged Smoking Outcome at 12 Weeks (End of Treatment)
To determine the efficacy of 12 weeks of varenicline therapy in achieving increased smoking abstinence rates in light smokers. Prolonged abstinence is defined as no smoking since 2 weeks after the target quit date.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Prolonged Smoking Outcome at 12 Weeks (End of Treatment) | 18 participants |
| Placebo | Prolonged Smoking Outcome at 12 Weeks (End of Treatment) | 4 participants |
p-value: 0.00195% CI: [2.2, 24]Regression, Logistic
Secondary
Point Prevalence Smoking Outcome at 24 Weeks (End of Study)
To determine the efficacy of 12 weeks of varenicline therapy in achieving increased smoking abstinence rates at 6 months in light smokers. Point prevalence is defined as no smoking in the past 7 days.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Point Prevalence Smoking Outcome at 24 Weeks (End of Study) | 18 participants |
| Placebo | Point Prevalence Smoking Outcome at 24 Weeks (End of Study) | 10 participants |
p-value: 0.04795% CI: [1, 6.3]Regression, Logistic
Secondary
Prolonged Smoking Outcome at 24 Weeks (End of Study)
To determine the efficacy of 12 weeks of varenicline therapy in achieving increased smoking abstinence rates at 6 months in light smokers. Prolonged abstinence is defined as no smoking since 2 weeks after the target quit date.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Prolonged Smoking Outcome at 24 Weeks (End of Study) | 14 participants |
| Placebo | Prolonged Smoking Outcome at 24 Weeks (End of Study) | 4 participants |
p-value: 0.00995% CI: [1.5, 16.5]Regression, Logistic