Combination of E-cigarettes and Varenicline for Tobacco Harm Reduction

Study Overview
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Brief Summary
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This open-label study will explore the impact of varenicline on the process of switching from combustible cigarettes (CC) to an e-cigarette. Varenicline is currently the most efficacious single pharmacotherapy for smoking cessation, and through its actions as an agonist or partial agonist at various nicotinic acetylcholine receptor subtypes, serves to diminish the rewarding effects of cigarette smoking. Diminishing the rewarding effects of smoking might facilitate the transition from CC to e-cigarettes. On the other hand, varenicline might attenuate the rewarding effects of nicotine-containing e-cigarettes as well, which could hamper the transition. Thus, the study will provide important information about the actions of varenicline on CC as well as e-cigarettes. There is no therapeutic intent in that smokers' nicotine/tobacco dependence will not be treated; the goal is to switch from one form of nicotine/tobacco dependence (CC) to dependence on a different tobacco product (e-cigarettes).

Official Title
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Combination of E-cigarettes and Varenicline for Tobacco Harm Reduction

Conditions
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Smoking Cessation, Harm Reduction

Intervention / Treatment
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* Drug: Varenicline
* Other: e-cigarette


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has signed the ICF and is able to read and understand the information provided in the consent form. Is 21 to 65 years of age (inclusive) at screening. Smokes at least 10 commercially available cigarettes per day (no brand restrictions), for the last 12 months. Has an expired air carbon monoxide reading of at least 10 ppm at screening. Interested in switching to an electronic cigarette. Willing and able to comply with the requirements of the study. Owns a smart phone with text message and data capabilities compatible with necessary surveys. Exclusion Criteria: Is unhealthy or cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason) as judged by the Investigator or designated medical staff based on all available assessments from the screening period (e.g., safety laboratory, vital signs, physical examination, Ankle-Brachial Index, ECG, concomitant medications and medical history). PHQ-9 score greater than 9, or a score greater than 0 on item #9 (Thoughts that you would be better off dead, or of hurting yourself in some way) at screening. Planned use of an FDA-approved smoking cessation product during the study. High blood pressure (systolic > 150 mmHg or diastolic >95 mmHg) at screening. Body mass index (BMI) less than 15.0 kg/m2 or greater than 40.0 kg/m2. Coronary heart disease, structural cardiac disease (including, but not limited to valvular heart disease or cardiac murmurs), cardiac dysrhythmias, syncope, cardiac chest pain, or history of heart attack or heart failure. Has received psychotherapy or behavioral treatments potentially impacting symptoms of depression, anxiety, or nicotine withdrawal within 30 days of screening, or during the study. Taking antidepressants, psychoactive medications (e.g. antipsychotics, benzodiazepines, hypnotics) or medications that prolong QTc. Use of any of these products in the past 30 days: a. Illegal drugs (or if the urine drug screen is positive for cocaine, THC, amphetamines, methamphetamines, or opiates); b. Experimental (investigational) drugs that are unknown to subject; c. Chronic opiate use. Use of smokeless tobacco (chewing tobacco, snuff), cigars (except for Black & Mild cigars or Cigarillos), pipes, hookah, e-cigarettes, nicotine replacement therapy or other smoking cessation treatments within 14 days of screening. Pregnant or nursing (by self-report) or has a positive pregnancy test. Enrollment requirements met.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Varenicline plus e-cigarette<br>Participants enrolled in the study will receive a G6 e-cigarette at V2 for ad libitum use. The FDA approved starter kit of varenicline will be provided to participants at V3 (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7) along with additional G6 cartomizers. After the first week of varenicline, participants will receive the FDA-approved standard dose of varenicline (1 mg twice daily) and will continue to receive enough G6 cartomizers for the next 11 weeks. | Drug: Varenicline<br>* 0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7; then 1 mg twice daily for the remaining 11 weeks.<br>* Other names: Chantix;Other: e-cigarette<br>* Each G6 prefilled cartomizer contains a 50/50 blend nicotine salt with 35mg nicotine strength.<br>* Other names: Halo G6;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participant Reporting Continuous Complete Switching From Cigarettes to Halo G6 | The primary switching outcome will be smoking abstinence during weeks 8-11 post-switching date. Complete switching from combustible cigarette use at each time point will be defined by a self-report of no cigarette smoking (not even a puff) since the prior session. | Weeks 8-11 | 
| Number of Participants Confirmed (by Expired Air CO) to Have Switched From Cigarettes to Halo G6 | The primary switching outcome will be smoking abstinence during weeks 8-11 post-switching date. Complete switching from combustible cigarette use at each time point confirmed by an expired air CO reading of less than 5 ppm. | Weeks 8-11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Point Abstinence From Smoking Cigarettes at 6 Months Post-Switch | Point abstinence will be defined by a self-report of no cigarette smoking (not even a puff) in the last seven days at six months post-switch. | 6 months |