Phase 3 Trial Evaluating the Efficacy and Safety of Cytisinicline for Vaping Cessation in Adults Using Nicotine-Containing E Cigarettes

Inclusion Criteria: * Male or female subjects, age ≥18 years. * Test positive for cotinine using a point-of-care Oral Fluid Screening Device (OFD) with positive detection at ≥30 ng/mL cotinine. * 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. * Failed at least one previous attempt to stop vaping with or without therapeutic support. * Willing to initiate study treatment on the day after randomization and set a quit date within Day 7 and Day 14. * 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 3 months prior to study randomization, any combustible cigarettes, other combustible tobacco products or non-combustible tobacco products such as heat not burn products or nicotine pouches (ie, dual users). * Currently smoking/vaping cannabis or having smoked or vaped cannabis within 4 weeks (28 days) prior to study randomization or planned use while on study. Other methods of cannabis consumption, eg, edibles, tinctures, capsules, topicals, etc. are allowed. * Expired Carbon Monoxide (CO) levels ≥6 ppm, indicating recent combustible tobacco or cannabis smoking. * A score of 0-3 on the Penn State e-Cigarette Dependence Index indicating no dependence. * More than 1 study subject in same household during the study treatment period. * Known hypersensitivity to any of the excipients, previous cytisinicline treatment in a prior clinical study, or any previous use of cytisinicline. * Positive urinary drugs of abuse screen determined within 28 days before the first dose of study drug. (Note: Although THC is part of the standard drug screen, it is not necessarily exclusionary. Refer to exclusion criteria #2). * Clinically significant abnormal serum chemistry or hematology values, as determined by the investigator, within 28 days of randomization. * Clinically significant abnormalities on screening visit 12-lead ECG, as determined by the investigator, after minimum of 5 minutes in supine position within 28 days of randomization. * Recent history (within 3 months prior to screening) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident or hospitalization for congestive heart failure. * Current uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg). * Currently psychotic or having had a psychotic event in the 3 months prior to the screening visit. 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 3, 4 or 5 OR YES to any suicidal behavior question on the C-SSRS with clear suicidal intent or suicide attempt within the last 10 years). * Current symptoms of moderate to severe depression (depression score ≥11 using depression questions on the Hospital Anxiety and Depression Scale \[HADS\] at screening visit). * Renal impairment defined as a creatinine clearance (CrCl) \<60 mL/min at screening visit (estimated with the Cockroft-Gault equation and reported by the central laboratory). * Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.0 x the upper limit of normal (ULN) at screening visit. * Recent history or symptoms (within 4 weeks of randomization) of unstable respiratory disease (eg, pneumonia, product-use associated lung injury or EVALI, etc). * Women who are pregnant or breast-feeding. * Female subjects of childbearing potential who do not agree to use acceptable methods of birth control during the study. Acceptable methods of birth control include: * True abstinence: When this is in line with the preferred and usual lifestyle of the subject. \[Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\]. * Barrier methods: * diaphragm * cervical cap * contraceptive sponge * intrauterine device (IUD) * double barrier method (condom with spermicide) * Hormonal methods: * Oral contraceptives * Vaginal ring such as NuvaRing * Skin patch such as Xulane * Injection such as Depro-Provera * Implantable rod such as Nexplanon * Intrauterine device (IUD) * Participation in a clinical study with an investigational drug or biologic in the 4 weeks prior to study randomization. * Use of any smoking cessation medications (bupropion, varenicline, nortriptyline, or any nicotine replacement therapy \[NRT\]) in the 4 weeks prior to study randomization 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 (eg, 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.