A Study of Cytisinicline for Vaping Cessation in Adult Smokers

Study Overview
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Brief Summary
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This placebo-controlled Phase 2 study is being conducted at sites within the United States to evaluate the safety profile of 3 mg cytisinicline administered TID for 12 weeks.

Official Title
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A Multicenter, Double-blind, Randomized, Placebo-controlled Phase 2 Trial Evaluating the Efficacy and Safety of Cytisinicline in Adults Using Nicotine-containing E-cigarettes

Conditions
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Vaping, E-Cig Use

Intervention / Treatment
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* Drug: cytisinicline
* Drug: Placebo
* Behavioral: Behavioral support


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects, age ≥ 18 years. Test positive for cotinine using the Alere iScreen® OFD Cotinine Oral Fluid Screening Device (Positive testing at ≥ 30 ng/mL cotinine level). Current daily nicotine-containing electronic cigarette usage as recorded in a screening diary for at least 7 consecutive days. Willing to bring the e-cigarette or nicotine device used to the clinical site so that the specific product type, flavor, and nicotine level can be documented. Willing to initiate study treatment on the day after randomization and set a quit date within 7-14 days of starting treatment. Willing to actively participate in the study's vaping cessation behavioral support provided throughout the study. Able to fully understand study requirements, willing to participate, and comply with dosing schedule. Sign the Informed Consent Form. Exclusion Criteria: Currently smoking, or having smoked within 4 weeks prior to study randomization, any combustible cigarettes, other combustible tobacco products or non-combustible tobacco products (such as heat not burn products) (i.e., dual users). Expired carbon monoxide (CO) levels ≥ 10 ppm, indicating recent combustible tobacco use. More than 1 study participant in same household during the study treatment period. Known hypersensitivity to cytisinicline or any of the excipients. Positive urinary drugs of abuse screen determined within 28 days before the first dose of cytisinicline (Note: tetrahydrocannabinol (THC) is not part of the abuse screen). Clinically significant abnormal serum chemistry or hematology values within 28 days of randomization (i.e., requiring treatment or monitoring). Clinically significant abnormalities in 12-lead electrocardiogram determined after minimum of 5 minutes in supine position within 28 days of randomization (i.e., requiring treatment or further assessment). Recent history (within 3 months) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident or hospitalization for congestive heart failure. Current uncontrolled hypertension (blood pressure ≥ 160/100 mmHg). Documented diagnosis of schizophrenia or bipolar psychiatric illness; currently psychotic; having suicidal ideation within the last 3 months (corresponding to question 4 or 5 on the Columbia - Suicide Severity Rating Scale [C-SSRS]); or current symptoms of moderate to severe depression (depression score ≥ 11 on the HADS) within the last 3 months. Renal impairment defined as a creatinine clearance (CrCl) < 60 mL/min (estimated with the Cockroft-Gault equation). Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.0 x the upper limit of normal (ULN). Recent history or symptoms (within 4 weeks of randomization) of unstable respiratory disease (e.g., pneumonia, product-use associated lung injury or e-cigarette or vaping use-associated lung injury [EVALI], etc.) Women who are pregnant or breast-feeding. Male or female subjects of childbearing potential who do not agree to use acceptable methods of birth control starting at the time of consent, during the study treatment period, and continuing for one month after ending study treatment. Participation in a clinical study with an investigational drug in the 4 weeks prior to study randomization. Use of other smoking cessation medications (bupropion, varenicline, nortriptyline, or any nicotine replacement therapy [NRT]) in the 4 weeks prior to study randomization, any previous cytisine use, or planned use of these or other nicotine replacement medications during the study. Any planned use during the study of combustible cigarettes or other nicotine-containing, non-vaping products (e.g., pipe tobacco, cigars, snuff, smokeless tobacco, hookah, ZYN pouches, etc). Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + Behavioral Support<br>one placebo tablet orally (PO) three times daily (TID) plus behavioral support for 12 weeks | Drug: Placebo<br>* film-coated oral tablets containing matched placebo<br>Behavioral: Behavioral support<br>* Behavioral support sessions by a qualified study site staff member will be participant-driven and will include direct engagement with the participant about their attempt to quit vaping. Each session will last approximately 10 minutes.<br>|
| Experimental: Cytisinicline + Behavioral Support<br>one cytisinicline tablet PO TID plus behavioral support for 12 weeks | Drug: cytisinicline<br>* film-coated oral tablets containing 3 mg cytisinicline<br>* Other names: cytisine;Behavioral: Behavioral support<br>* Behavioral support sessions by a qualified study site staff member will be participant-driven and will include direct engagement with the participant about their attempt to quit vaping. Each session will last approximately 10 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Vaping Abstinence During Weeks 9 to 12 | Vaping abstinence using quantitative saliva cotinine levels at < 10 ng/mL for biochemical verification and participants' self-report of no vaping in the past 7 days. | Week 9-12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Vaping Abstinence During Weeks 3 to 6 | Vaping abstinence using quantitative saliva cotinine levels at < 10 ng/mL for biochemical verification and participants' self-report of no vaping in the past 7 days. | Weeks 3-6 | 
| Proportion of Participants With Vaping Abstinence During Weeks 6 to 9 | Vaping abstinence using quantitative saliva cotinine levels at < 10 ng/mL for biochemical verification and participants' self-report of no vaping in the past 7 days. | Weeks 6-9 | 
| Number of Participants Who Achieve Vaping Abstinence at Any Time Between Week 2 and Week 12 (Seven-Day Point Prevalence Rates) | Vaping abstinence using quantitative saliva cotinine levels at < 10 ng/mL for biochemical verification and participants' self-report of no vaping in the past 7 days. | Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 | 
| Changes From Baseline in Quantitative Cotinine Levels from Week 2 to Week 12 | Changes in nicotine vaping using weekly quantitative cotinine levels from Week 2 to Week 12. | Baseline, Weeks 2-12 | 
| Proportion of Participants With Vaping Abstinence During Weeks 9 to 16 | Vaping abstinence using quantitative saliva cotinine levels at < 10 ng/mL for biochemical verification and participants' self-report of no vaping in the past 7 days. | Weeks 9 to 16 |