Clinical trial NCT03303911 (phase 1/phase 2, status: terminated)
Conditions: smoking cessation
ICD codes: Y36.881S, Y36.891S, Y36.880S, Y36.881A, Y36.881D, Y36.890S, Y36.891A
Drugs: cytisine
SMILES: O=C1C=CC=C2[C@H]3CNC[C@H](C3)CN12
Reason stopped: 
    it has been difficult to recruit participants meeting study entry criteria that are >65 years
    of age and not for any safety reasons.
  
Eligibility criteria:

        Inclusion Criteria:

          1. Regular moderate cigarette smokers (minimum 10 cigarettes per day) who want to stop
             smoking.

          2. Urine cotinine >500 ng/mL.

          3. Expired air carbon monoxide (CO) > 11 parts per million (no cigarette 1 hour before
             test).

          4. Healthy males and females 18-65+ years of age.

               1. If a female subject of child bearing potential, a negative pregnancy test at
                  screening and admission and willing to use an effective method of contraception
                  (unless of non-childbearing potential or where abstaining from sexual intercourse
                  is in line with the preferred and usual lifestyle of the subject) from first dose
                  until 3 months after last dose of cytisine.

               2. If a female subject of non-child bearing potential, a negative pregnancy test at
                  screening and admission. For the purposes of this study, this is defined as the
                  subject being amenorrheic for at least 12 consecutive months or at least 4 months
                  post-surgical sterilisation (including bilateral fallopian tube ligation or
                  bilateral oophorectomy with or without hysterectomy). Menopausal status will be
                  confirmed by demonstrating at screening that levels of follicle stimulating
                  hormone (FSH) fall within the respective pathology reference range. In the event
                  a subject's menopause status has been clearly established (for example, the
                  subject indicates she has been amenorrheic for 10 years), but FSH levels are not
                  consistent with a post-menopausal condition, determination of subject eligibility
                  will be at Investigator's discretion following consultation with the Sponsor.

               3. If a male subject, willing to use an effective method of contraception (unless
                  anatomically sterile or where abstaining from sexual intercourse is in line with
                  the preferred and usual lifestyle of the subject) from first dose until 3 months
                  after last dose of cytisine.

          5. Subject with no clinically significant abnormal serum biochemistry, haematology and
             urine examination values within 28 days before the first dose of cytisine.

          6. Subject with negative urinary drugs of abuse screen, determined within 28 days before
             the first dose of cytisine (a positive alcohol result may be repeated at
             Investigator's discretion).

          7. Subject with negative human immunodeficiency virus (HIV), hepatitis B surface antigen
             (Hep B) and hepatitis C virus antibody (Hep C) results.

          8. Subject with no clinically significant abnormalities in 12-lead ECG determined after
             minimum of 5 minutes in supine position within 28 days before the first dose of
             cytisine.

          9. Subject with no clinically significant abnormalities in vital signs (systolic blood
             pressure between 90-150 mmHg (age 18-65) and 90-160 mmHg (age >65), diastolic blood
             pressure (DBP) between 50 and 90 mmHg, and pulse rate (PR) between 40 110 bpm,
             measured on the dominant arm after minimum of 5 minutes in supine position) determined
             within 28 days before first dose of cytisine.

         10. Subject must be available to complete the study (including in-clinic stays and post
             study follow-up) and comply with study restrictions.

         11. Subject must provide written informed consent to participate in the study.

        Exclusion Criteria:

          1. Treatment with smoking cessation medications (bupropion, varenicline, any nicotine
             replacement therapy) within 8 weeks of first dose of cytisine.

          2. Use of other forms of nicotine (e-cigarettes, smokeless tobacco) within 8 weeks of
             first dose of cytisine or are planning to use these products during study.

          3. Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or
             any of the excipients in the Tabex formulation.

          4. History of severe hypersensitivity reactions to any other drugs.

          5. Current treatment with antihypertensive medicinal products, statins, tuberculostatics,
             cholinomimetics or anticholinesterase medicinal products.

          6. History of any medical condition (e.g. gastrointestinal, renal or hepatic) or surgical
             condition (e.g. cholecystectomy, gastrectomy) that may affect drug pharmacokinetics
             (absorption, distribution, metabolism or excretion).

          7. Female subjects who are breast feeding.

          8. Difficulty in donating blood on either arm or known history.

          9. History of alcoholism or drug abuse within last 2 years.

         10. Use of non-prescription drugs, including vitamins, herbal and dietary supplements
             within 14 days (or 5 half-lives, whichever is longer) prior to the first dose of
             cytisine, unless in the opinion of the Principal Investigator the medication will not
             interfere with the study procedures or compromise subject safety.

         11. Participated in any investigational drug clinical trial within the previous 3 months
             or a marketed drug trial within the previous 30 days prior to randomisation on Day 1.

         12. Donation of 450 mL or more blood or had history of significant blood loss due to any
             reason or had plasmapheresis within 3 months before the first dose of cytisine.

         13. Inability to communicate well with Principal Investigator or designees (i.e., language
             problem, poor mental development or impaired cerebral function).

         14. Any other condition that the Principal Investigator considers making the subject
             unsuitable for this study.