A Second Study of Cytisinicline for Smoking Cessation in Adult Smokers

Study Overview
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Brief Summary
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This placebo-controlled Phase 3 study is being conducted at sites within the United States to evaluate 3 mg cytisinicline TID for treatment duration of 42 days/6 weeks as well as repeating that duration for a total of 84 days/12 weeks treatment.

Official Title
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A Second Multicenter, Double-blind, Randomized, Placebo-controlled Phase 3 Trial Evaluating the Efficacy and Safety of Cytisinicline in Adult Smokers

Conditions
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Smoking Cessation

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. Current daily cigarette smokers (averaging at least 10 cigarettes per day upon completing a 7-day screening smoking diary) and who intend to quit smoking. Expired air carbon monoxide (CO) ≥ 10 ppm. Failed at least one previous attempt to stop smoking with or without therapeutic support. Willing to initiate study treatment on the day after randomization and set a quit date within 5-7 days of starting treatment. Willing to actively participate in the study's smoking cessation behavioral support provided throughout the study. Able to fully understand all study requirements, willing to participate, and comply with dosing schedule. Sign the Informed Consent Form. Exclusion Criteria: More than 1 study participant in same household during the 12-week treatment period. Previous cytisinicline treatment in a prior clinical study or any other cytisine usage. 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. Clinically significant abnormal serum chemistry or hematology values within 28 days of randomization (ie, requiring treatment or monitoring). Clinically significant abnormalities in 12-lead ECG determined after minimum of 5 minutes in supine position within 28 days of randomization (ie, 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). Currently psychotic or having had a psychotic event within 3 months. If any subject becomes psychotic during the study, they must be removed from treatment and/or additional study visits. Currently having suicidal ideation or risk for suicide (Yes to either question 4 or question 5 OR Yes to any suicidal behavior question on the C-SSRS with clear suicidal intent or previous attempt). Current symptoms of moderate to severe depression (depression score ≥11on the HADS). 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). 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 during the study treatment period. Participation in a clinical study with an investigational drug in the 4 weeks prior to randomization. Treatment with other smoking cessation medications (bupropion, varenicline, nortriptyline, or any nicotine replacement therapy [NRT]) in the 4 weeks prior to randomization or planned use of these other smoking cessation medications during the study. Use within the 2 weeks prior to randomization or planned use during the study of non-cigarette and/or noncombustible nicotine products (pipe tobacco, cigars, snuff, smokeless tobacco, hookah, e-cigarettes/vaping) or marijuana smoking or vaping. 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 subject about their attempt to quit smoking. Each session will last approximately 10 minutes.<br>|
| Experimental: Cytisinicline + Placebo + Behavioral Support<br>one cytisinicline tablet PO TID plus behavioral support for 6 weeks followed by one placebo tablet PO TID plus behavioral support for 6 weeks | Drug: Cytisinicline<br>* film-coated oral tablets containing 3 mg cytisinicline<br>* Other names: Cytisine;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 subject about their attempt to quit smoking. 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 subject about their attempt to quit smoking. 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 Smoking Abstinence During the Last 4 Weeks of 6 Weeks Cytisinicline Treatment Versus Placebo Treatment (Wk 3-6) | Smoking abstinence as verified by weekly expired carbon monoxide (CO) measurements ≤ 10 parts per million (ppm). | Week 3-6 | 
| Proportion of Participants With Smoking Abstinence During the Last 4 Weeks of 12 Weeks Cytisinicline Treatment Versus Placebo Treatment (Wk 9-12) | Smoking abstinence as verified by weekly expired carbon monoxide (CO) measurements ≤ 10 parts per million (ppm). | Week 9-12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Continuous Smoking Abstinence to Week 24 | Smoking abstinence as verified by monthly expired CO measurements ≤ 10 ppm. | Week 24 | 
| Proportion of Participants Who are Relapse-Free at Week 24 | Relapse is defined as participant reported resuming smoking or an expired CO measure ≥ 10 ppm. | Week 24 |