A Single Dose-escalation Study of Cytisine in Adult Smokers
Condition: Smoking Cessation
Intervention: cytisine; placebo
Intervention description: cytisine film-coated oral tablet; matching placebo oral tablet
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The objectives of this study are:

        1. To assess the tolerability and safety of cytisine as a single oral dose.

        2. To define the Cmax levels associated to the occurrence of dose-limiting adverse events.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects must meet ALL of the following criteria to be eligible for inclusion into the
        study:

          1. Free written informed consent prior to any procedure required by the study.

          2. Male or female subjects, age ≥18 years, at the time of signing the informed consent.

          3. Current daily cigarette smokers (averaging at least 10 cigarettes per day in the past
             30 days).

          4. Expired air carbon monoxide (CO) ≥10 ppm.

          5. Able to swallow multiple tablets at one time.

          6. Able to fully understand, comply with all study requirements.

        Exclusion Criteria:

        Subjects meeting ANY of the following exclusion criteria will NOT be eligible for inclusion
        into the study at screening.

          1. Known hypersensitivity to cytisine or any of the excipients.

          2. Known severe hypersensitivity to any other drug.

          3. Positive urinary drugs of abuse screen, determined within 28 days before
             cytisine/placebo dosing.

          4. Positive ethanol breath test.

          5. Clinically significant abnormal serum chemistry, hematology, coagulation or urinalysis
             values within 28 days of randomization (i.e. requiring treatment or monitoring).

          6. Clinically significant abnormalities in 12-lead echocardiogram (ECG) determined after
             minimum of 5 minutes in supine position within 28 days of randomization (i.e.
             requiring treatment or further assessment).

          7. Body Mass Index (BMI) classification for being underweight (<18.5 kg/m2) or having
             ≥Class 2 obesity (≥35 kg/m2).

          8. History of acute myocardial infarction, unstable angina, stroke, cerebrovascular
             incident, cardiac arrhythmia, or hospitalization for congestive heart failure.

          9. Blood pressure ≥160/100 mmHg, measured on the dominant arm, after at least 3 minutes
             in supine position.

         10. Creatinine clearance (CrCl) <80 mL/min (estimated with the Cockroft-Gault equation).

         11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.0 x the upper
             limit of normal (ULN).

         12. Any inability to comply with study restrictions (See Section 9)

         13. Any inability or difficulty in fasting.

         14. Difficulty in donating blood on either arm.

         15. If woman of childbearing potential, positive result in serum beta-human chorionic
             gonadotropin (hCG) pregnancy test.

         16. Women who are breast-feeding.

         17. Subjects who do not agree to use acceptable methods of birth control during the study
             (See Section 9.4).

         18. Participation in a clinical study with an investigational drug within the previous 2
             months.

         19. Participation in more than 2 clinical trials within the previous 12 months.

         20. Any other reason that the investigator views the subject should not participate or
             would be unable to fulfill the requirements for the study.

             Subjects meeting ANY of the following exclusion criteria will NOT be eligible for
             inclusion into the study at admission to each cohort.

         21. Any recent disease or condition or treatment that, according to the Investigator,
             would put the subject at undue risk due to study participation.

         22. Positive urinary drugs of abuse screen.

         23. Positive ethanol breath test.

         24. If female of childbearing potential, positive result in urine beta-hCG pregnancy test.

         25. Any other reason that the investigator views the subject should not participate or
             would be unable to fulfill the requirements for the study.