A Study in Healthy Volunteers to Investigate the Effect of Food on the Bioavailability of Cytisine
A Study in Healthy Volunteers to Investigate the Effect of Food on the Bioavailability of Cytisine
This will be an open-label, randomised, 2-period, single-dose crossover study to determine
 the comparative bioavailability of cytisine following single-dose administration in healthy
 male and female subjects under fed and fasted conditions.

 The study will be comprised of a pre-study screen, followed by 2 treatment periods (1 and 2)
 and a post-study follow-up.
Inclusion Criteria:

 1. Healthy males and females between 18 and 55 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 investigational medicinal product (IMP).

 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 IMP.

 2. Subject with a body mass index (BMI) of 18-32 kg/m^2. BMI = body weight in kg /
 [height in m]^2.

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

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

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

 6. 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 IMP.

 7. Subject with no clinically significant abnormalities in vital signs (systolic blood
 pressure between 90-150 mmHg, 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 IMP.

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

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

 Exclusion Criteria:

 1. Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or
 any of the excipients in the Tabex formulation (lactose, cellulose, talc, magnesium).

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

 3. 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).

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

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

 6. Regular nicotine intake (e.g., smoking, nicotine patch, nicotine chewing gum or
 electronic cigarettes) within previous 3 months and inability to refrain from nicotine
 intake from Screening until end of study.

 7. Use of prescription or 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 IMP, unless in the opinion of the Investigator the medication will not
 interfere with the study procedures or compromise subject safety.

 8. Participated in any investigational drug clinical trial within the previous 3 months
 or a marketed drug trial within the previous 30 days prior to randomization on Day 1
 of Period 1.

 9. 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 IMP.

 10. Any special food restrictions that may hinder ability to consume the high fat
 breakfast provided during the study; such as lactose intolerance, vegan, low-fat, low
 sodium, etc.

 11. Any inability or difficulty in fasting.

 12. Inability to communicate well with Investigators (i.e., language problem, poor mental
 development or impaired cerebral function).

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