Trial of Cytisine in Adult Smokers

A Multicenter, Double-blind, Randomized, Placebo-controlled Phase 2b Trial of Cytisine in Adult Smokers

This placebo-controlled Phase 2b trial is being conducted at sites within the United States (US) to evaluate the effectiveness cytisine dosage (1.5 mg, 3.0 mg) and administration schedule (commercial titration versus simplified 3 times daily [TID] schedule) within a 25-day treatment period.

Inclusion Criteria:

1. Male or female subjects, age ≥ 18 years.
2. Current daily cigarette smokers (averaging ≥ 10 cigarettes per day upon completing a 7-day screening diary) and who intend to quit smoking.
3. Expired air carbon monoxide (CO) ≥ 10 parts per million (ppm).
4. Failed at least one previous attempt to stop smoking with or without therapeutic support.
5. Willing to initiate study treatment on the day after randomization and set a quit date that is 5-7 days after starting treatment.
6. Willing to actively participate in the study's smoking cessation behavioral support provided throughout the study.
7. Able to fully understand all study requirements, willing to participate, comply with dosing schedule, and sign the Informed Consent Form.

Exclusion Criteria:

1. Known hypersensitivity to cytisine or any of the excipients.
2. Positive urinary drugs of abuse screen, determined within 28 days before the first dose of cytisine.
3. Clinically significant abnormal serum chemistry or hematology values within 28 days of randomization (i.e. requiring treatment).
4. Clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined after minimum of 5 minutes in supine position within 28 days of randomization (i.e. requiring treatment or further assessment).
5. Body mass index (BMI) classification for being underweight (< 18.5 kg/m^2) or having ≥ Class 2 obesity (≥ 35 kg/m^2).
6. Recent history (within 3 months) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident or hospitalization for congestive heart failure.
7. Current uncontrolled hypertension (blood pressure ≥ 160/100 mmHg).
8. Documented diagnosis of schizophrenia or bipolar psychiatric illness; currently psychotic; having suicidal ideation (Suicide Behaviors Questionnaire-Revised [SBQ-R] score ≥ 7); or current symptoms of moderate to severe depression (Hospital Anxiety and Depression Scale [HADS] score ≥ 11).
9. Renal impairment defined as a creatinine clearance (CrCl) < 60 mL/min (estimated with the Cockroft-Gault equation) or hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.0 times the upper limit of normal (ULN).
10. Women who are pregnant or breast-feeding.
11. Male or Female subjects of child bearing potential who do not agree to use acceptable methods of birth control during the study treatment period.
12. Participation in a clinical study with an investigational drug within 4 weeks of randomization.
13. Treatment with other smoking cessation medications (bupropion, varenicline, nortriptyline, or any nicotine replacement therapy [NRT]) within 4 weeks of randomization or planned use of these other smoking cessation medications during the study.
14. Use within 2 weeks of randomization or planned use during the study of non-cigarette nicotine products (e-cigarettes, pipe tobacco, cigars, snuff, chewing tobacco, hookah) or marijuana vaping or smoking.
15. Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.