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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Cytisine 1.5 mg Film-Coated Tablets
Simbec Research Ltd
Merthyr Tydfil, United Kingdom
Plasma Cytisine Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: Total Area Under the Curve From Time Zero to Infinity (AUC0-∞)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: Time of Occurrence of Cmax (Tmax)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: AUC From Time Zero to the Last Sampling Time (AUC0-t)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: Residual Area, or Percentage of Extrapolated Part for the Calculation of AUC0-∞ (AUC%)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: Apparent Terminal Elimination Rate Constant (Lambda z)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
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Plasma Cytisine PK: Apparent Terminal Elimination Half-Life (t1/2)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Urine Cytisine PK: Amount Excreted in Urine Over Time (Ae)
Time frame: Pre-dose (within 30 minutes prior to first dose); 0-2 hours, 2-4 hours, 4-8 hours, 8-12 hours and 12-24 hours post-dose
Urine Cytisine PK: Percentage of Drug Excreted in Urine (Ae%)
To assess the renal elimination of cytisine via measurement of urinary concentrations of cytisine.
Time frame: Pre-dose (within 30 minutes prior to first dose); 0-2 hours, 2-4 hours, 4-8 hours, 8-12 hours and 12-24 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuation of Study Drug Due to AEs, by Severity and Relationship
An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have a causal relationship with the treatment. TEAEs are defined as AEs not present prior to first administration of investigational product, or AEs present before first administration of study drug that worsen after the subject receives the first dose of study drug. A serious adverse event (SAE) is defined as an AE that: results in death; is life-threatening; requires hospitalization or prolongs existing inpatient's hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medical event which requires medical intervention to prevent any of the above outcomes. Event severity was categorized as mild, moderate, or severe. Relationship of event to study drug was categorized as definite, probably, possible, unlikely, not related, or not applicable (N/A).
Time frame: Day -1 to Day 7 plus 6-8 days (post-study follow-up)