Trial of Cytisine in Adult Smokers
Condition: Smoking Cessation
Intervention: Cytisine; Placebo Comparator; Behavioral support
Intervention description: film coated tablet containing 1.5 mg cytisine in a single tablet; 1.5 mg cellulose powder to match final weight of the cytisine tablet; 12 behavioral support sessions by a qualified staff member plus supportive literature and online resources
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 254.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.