Smoking Cessation, Tobacco Dependence, Withdrawal Symptoms
Conditions
Brief summary
The primary goal of the proposed research is to test whether varenicline (Chantix) is safe and effective as an over-the-counter (OTC) medication.
Detailed description
Given the recent research on varenicline showing that it is more effective than nicotine patch and bupropion, and with the removal of the box warning, research is needed to assess whether smokers can use varenicline without a prescription and formal behavioral support. To test this, the primary goal of the proposed research is to test whether varenicline is a candidate for switching from prescription (Rx) to OTC, and whether a dose lower than that currently approved is as effective in an OTC environment. To understand the within-person mechanisms explaining how and when OTC varenicline might improve cessation outcomes, the investigators also propose to assess experience with OTC varenicline via (a) ecological momentary assessment (EMA). Primary Objectives: 1. To assess the safety and effectiveness of the current FDA-approved 1 mg b.i.d. varenicline for smoking cessation in comparison with placebo when used in a simulated OTC study condition. 2. To assess the safety and effectiveness of .5mg b.i.d. varenicline in comparison with 1mg b.i.d. varenicline and placebo when used in a simulated OTC study condition.
Interventions
DRUG1.0mg Varenicline b.i.d.
Varenicline is classified as a selective nicotine receptor partial agonist (SNRPA) that works both to stimulate the nicotine receptor and block smoking reward at the α4β2 nicotinic receptor subtype.
DRUG0.5mg Varenicline b.i.d.
Varenicline is classified as a selective nicotine receptor partial agonist (SNRPA) that works both to stimulate the nicotine receptor and block smoking reward at the α4β2 nicotinic receptor subtype.
DRUG0.0mg placebo Varenicline b.i.d.
Product that looks like active varenicline, but contains no active ingredient
Sponsors
National Institute on Drug Abuse (NIDA)
Los Angeles Clinical Trials
University of Nevada, Reno
Pfizer
Arizona State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
for the In-person Cohort 1. 21 years of age or older 2. Self-reported daily smoker 3. Breath CO \> 10ppm 4. Motivated to quit smoking completely within five weeks of the Screening Visit (\>5 on reported motivation) 5. Capable of and agree to complete study requirements 6. Literate in English, self-report 7. Must be available for the duration of study 8. Informed consent obtained 9. Willing and able to provide additional data between visits using ecological momentary assessment (EMA) 10. Must own study compatible smart-phone (iPhone or Android)
Exclusion criteria
for the In-person Cohort 1. Any self-report, diagnosis or treatment of heart attack, unstable angina, angioedema, seizures, cerebrovascular accident (CVA) within the last six months. 2. Any self-report, diagnosis or treatment of bipolar, schizophrenia or suicidal ideation within the last six months. (For suicidal ideation a score of ≥7 on the Suicidal Behavior Questionnaire, see Appendix 15) 3. Self-report of diagnosis or treatment for depression within the past six months, unless participant has written permission by their healthcare provider to participate 4. Systolic blood pressure 160 or higher and/or diastolic blood pressure 100 or higher (see site applicable SOP for Evaluating and Reporting Blood Pressure and Appendices 5 and 6 for participant handouts) 5. History of renal disease 6. Allergy to any of the ingredients in varenicline 7. Participation in another smoking cessation program or any type of clinical trial in the past 3 months 8. Use of any smoking cessation medication in the past three months 9. Any other medical condition(s) which the licensed study physician deems unacceptable for participation in this study 10. Positive drug screen indicating possible substance abuse (eg opiates, amphetamines, benzodiazepines, cocaine or other substances), unless participant can show that the medication has been prescribed by licensed clinical provider. 11. Consume greater than 21 alcohol drinks per week. 12. No two members of the same household may participate in this study 13. No study staff or their immediate family may participate in the study 14. Females who are pregnant, breast feeding, or not currently using a medically approved form of birth control and unwilling to do so. Acceptable methods of birth control include abstinence, oral contraceptives, the contraceptive patch, the contraceptive ring, and condoms. Inclusion Criteria for the Remote Cohort 1. 21 years of age or older 2. Self-reported daily smoker 3. Positive cotinine from urine sample 4. Motivated to quit smoking completely within five weeks of the Screening Visit (\>5 on reported motivation) 5. Capable of and agree to complete study requirements 6. Literate in English, self-report 7. Must be available for the duration of study 8. Informed consent obtained 10\. Must own study compatible smart-phone (iPhone or Android) 11. Must be a current resident of the United States
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Who Have Continuous Abstinence as Verified by Breath Carbon Monoxide or Urine Cotinine | Week 12 | Participants will provide self reported smoking status that has been verified by breath carbon monoxide or cotinine - Continuous abstinence |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Breath Carbon Monoxide or Urine Cotinine Verified Abstinence From Smoking Cigarettes - Point Prevalence Abstinence | Week 12 visit | Participants will provide self reported smoking status that has been verified by breath carbon monoxide or cotinine - point prevalence abstinence |
| Breath Carbon Monoxide Verified Abstinence From Smoking Cigarettes | Week 26 | Participants who self report not smoking will be asked to have smoking status verified by breath carbon monoxide |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1.0mg Varenicline b.i.d. Days 1 through 3: 0.5mg, once daily; days 4 through 7: 0.5mg, twice daily; days 8 through end of treatment: 1mg, twice daily.
1.0mg Varenicline b.i.d.: Varenicline is classified as a selective nicotine receptor partial agonist (SNRPA) that works both to stimulate the nicotine receptor and block smoking reward at the α4β2 nicotinic receptor subtype. | 104 |
| 0.5mg Varenicline b.i.d. Days 1 through 3: 0.5mg, once daily; 0.5 mg b.i.d. dose starting at day 4 through the end of the study
0.5mg Varenicline b.i.d.: Varenicline is classified as a selective nicotine receptor partial agonist (SNRPA) that works both to stimulate the nicotine receptor and block smoking reward at the α4β2 nicotinic receptor subtype. | 104 |
| 0.0mg Placebo Varenicline b.i.d. Days 1 through 3: 0.0mg placebo once daily; days 4 through 7: 0.0mg placebo twice daily; days 8 through end of treatment: 0.0 mg placebo twice daily.
0.0mg placebo Varenicline b.i.d.: Product that looks like active varenicline, but contains no active ingredient | 105 |
| Total | 313 |
Baseline characteristics
| Characteristic | 1.0mg Varenicline b.i.d. | 0.5mg Varenicline b.i.d. | 0.0mg Placebo Varenicline b.i.d. | Total |
|---|---|---|---|---|
| Age, Continuous | 52.0 Years STANDARD_DEVIATION 10.5 | 51.4 Years STANDARD_DEVIATION 11.2 | 51.0 Years STANDARD_DEVIATION 12.3 | 51.5 Years STANDARD_DEVIATION 11.3 |
| Race/Ethnicity, Customized Race African-American | 40 Participants | 44 Participants | 35 Participants | 119 Participants |
| Race/Ethnicity, Customized Race AI/AN | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Caucasian | 60 Participants | 58 Participants | 63 Participants | 181 Participants |
| Race/Ethnicity, Customized Race Missing | 4 Participants | 0 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 104 participants | 104 participants | 105 participants | 313 participants |
| Sex: Female, Male Female | 56 Participants | 65 Participants | 33 Participants | 154 Participants |
| Sex: Female, Male Male | 47 Participants | 39 Participants | 72 Participants | 158 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 104 | 0 / 104 | 0 / 105 |
| other Total, other adverse events | 49 / 104 | 43 / 104 | 35 / 105 |
| serious Total, serious adverse events | 0 / 104 | 0 / 104 | 2 / 105 |
Outcome results
Primary
The Number of Participants Who Have Continuous Abstinence as Verified by Breath Carbon Monoxide or Urine Cotinine
Participants will provide self reported smoking status that has been verified by breath carbon monoxide or cotinine - Continuous abstinence
Time frame: Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1.0mg Varenicline b.i.d. | The Number of Participants Who Have Continuous Abstinence as Verified by Breath Carbon Monoxide or Urine Cotinine | 17 Participants |
| 0.5mg Varenicline b.i.d. | The Number of Participants Who Have Continuous Abstinence as Verified by Breath Carbon Monoxide or Urine Cotinine | 9 Participants |
| 0.0mg Placebo Varenicline b.i.d. | The Number of Participants Who Have Continuous Abstinence as Verified by Breath Carbon Monoxide or Urine Cotinine | 9 Participants |
Secondary
Breath Carbon Monoxide or Urine Cotinine Verified Abstinence From Smoking Cigarettes - Point Prevalence Abstinence
Participants will provide self reported smoking status that has been verified by breath carbon monoxide or cotinine - point prevalence abstinence
Time frame: Week 12 visit
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1.0mg Varenicline b.i.d. | Breath Carbon Monoxide or Urine Cotinine Verified Abstinence From Smoking Cigarettes - Point Prevalence Abstinence | 25 Participants |
| 0.5mg Varenicline b.i.d. | Breath Carbon Monoxide or Urine Cotinine Verified Abstinence From Smoking Cigarettes - Point Prevalence Abstinence | 12 Participants |
| 0.0mg Placebo Varenicline b.i.d. | Breath Carbon Monoxide or Urine Cotinine Verified Abstinence From Smoking Cigarettes - Point Prevalence Abstinence | 9 Participants |
Secondary
Breath Carbon Monoxide Verified Abstinence From Smoking Cigarettes
Participants who self report not smoking will be asked to have smoking status verified by breath carbon monoxide
Time frame: Week 26
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1.0mg Varenicline b.i.d. | Breath Carbon Monoxide Verified Abstinence From Smoking Cigarettes | 16 Participants |
| 0.5mg Varenicline b.i.d. | Breath Carbon Monoxide Verified Abstinence From Smoking Cigarettes | 11 Participants |
| 0.0mg Placebo Varenicline b.i.d. | Breath Carbon Monoxide Verified Abstinence From Smoking Cigarettes | 11 Participants |