A Second Study of Cytisinicline for Smoking Cessation in Adult Smokers

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 Columbia Suicide Severity Rating Scale [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.