Varenicline OTC Trial on Efficacy and Safety

Study Overview
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Brief Summary
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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
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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: 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. 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.

Official Title
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Varenicline OTC Trial on Efficacy and Safety

Conditions
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Tobacco Dependence, Withdrawal Symptoms, Smoking Cessation

Intervention / Treatment
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* Drug: 1.0mg Varenicline b.i.d.
* Drug: 0.5mg Varenicline b.i.d.
* Drug: 0.0mg placebo Varenicline b.i.d.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for the In-person Cohort 21 years of age or older Self-reported daily smoker Breath CO > 10ppm Motivated to quit smoking completely within five weeks of the Screening Visit (>5 on reported motivation) Capable of and agree to complete study requirements Literate in English, self-report Must be available for the duration of study Informed consent obtained Willing and able to provide additional data between visits using ecological momentary assessment (EMA) Must own study compatible smart-phone (iPhone or Android) Exclusion Criteria for the In-person Cohort Any self-report, diagnosis or treatment of heart attack, unstable angina, angioedema, seizures, cerebrovascular accident (CVA) within the last six months. 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) Self-report of diagnosis or treatment for depression within the past six months, unless participant has written permission by their healthcare provider to participate 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) History of renal disease Allergy to any of the ingredients in varenicline Participation in another smoking cessation program or any type of clinical trial in the past 3 months Use of any smoking cessation medication in the past three months Any other medical condition(s) which the licensed study physician deems unacceptable for participation in this study 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. Consume greater than 21 alcohol drinks per week. No two members of the same household may participate in this study No study staff or their immediate family may participate in the study 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 21 years of age or older Self-reported daily smoker Positive cotinine from urine sample Motivated to quit smoking completely within five weeks of the Screening Visit (>5 on reported motivation) Capable of and agree to complete study requirements Literate in English, self-report Must be available for the duration of study Informed consent obtained 10. Must own study compatible smart-phone (iPhone or Android) 11. Must be a current resident of the United States Exclusion Criteria for the Remote Cohort Any self-report, diagnosis or treatment of heart attack, unstable angina, angioedema, seizures, cerebrovascular accident (CVA) within the last six months. 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) Self-report of diagnosis or treatment for depression within the past six months, unless participant has written permission by their healthcare provider to participate History of renal disease Allergy to any of the ingredients in varenicline Participation in another smoking cessation program or any type of clinical trial in the past 3 months Use of any smoking cessation medication in the past three months Any other medical condition(s) which the licensed study physician deems unacceptable for participation in this study Consume greater than 21 alcohol drinks per week. No two members of the same household may participate in this study No study staff or their immediate family may participate in the study 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.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.0mg varenicline b.i.d.<br>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. | Drug: 1.0mg Varenicline b.i.d.<br>* 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.<br>|
| Experimental: 0.5mg varenicline b.i.d.<br>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 | Drug: 0.5mg Varenicline b.i.d.<br>* 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.<br>|
| Placebo Comparator: 0.0mg placebo varenicline b.i.d.<br>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. | Drug: 0.0mg placebo Varenicline b.i.d.<br>* Product that looks like active varenicline, but contains no active ingredient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breath carbon monoxide verified abstinence from smoking cigarettes | Participants will provide self reported smoking status that has been verified by breath carbon monoxide | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Participants will be asked to report adverse events | Week 2 visit | 
| Adverse events | Participants will be asked to report adverse events | Week 4 visit | 
| Adverse events | Participants will be asked to report adverse events | Week 8 visit | 
| Adverse events | Participants will be asked to report adverse events | Week 12 visit | 
| Adverse events | Participants will be asked to report adverse events | Week 13 visit | 
| Adverse events | A subset of participants will be asked to report adverse events via ecological momentary assessment (EMA). EMA asks questions via the participant mobile phone on multiple occasions, primarily at random | Change in adverse events from baseline to week 2 as measured by 5 daily EMA prompts | 
| Withdrawal symptoms and craving | Participants will be asked to report withdrawal symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). Scores can be between 0 (absent) - 4 (severe), and the average scores will be assessed. | week 2 visit | 
| Withdrawal symptoms and craving | Participants will be asked to report withdrawal symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). Scores can be between 0 (absent) - 4 (severe), and the average scores will be assessed. | week 4 visit | 
| Withdrawal symptoms and craving | Participants will be asked to report withdrawal symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). Scores can be between 0 (absent) - 4 (severe), and the average scores will be assessed. | week 8 visit | 
| Withdrawal symptoms and craving | Participants will be asked to report withdrawal symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). Scores can be between 0 (absent) - 4 (severe), and the average scores will be assessed. | week 12 visit | 
| Withdrawal symptoms and craving | Participants will be asked to report withdrawal symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). Scores can be between 0 (absent) - 4 (severe), and the average scores will be assessed. | week 13 visit | 
| Craving | Participants will be asked to report craving via ecological momentary assessment (EMA). EMA asks questions via the participant mobile phone on multiple occasions, primarily at random | change in craving from baseline to week 2 as measured by 5 daily EMA prompts | 
| 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 | Week 26 |