To assess the effect of food on the bioavailability of 3 mg cytisinicline following single-dose administration, and to evaluate the PK profile of 3 mg cytisinicline TID following multiple days of administration during Days 5-8.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
film-coated oral tablets containing 3 mg cytisinicline
BlueClinical Phase I
Porto, Portugal
Maximum Observed Plasma Concentration (Cmax)
Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
Time of Maximum Observed Plasma Concentration (Tmax)
Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
Time Point Prior to the First Quantifiable Concentration (Tlag)
Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
Time of Last Quantifiable Observed Concentration (Tlast)
Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
Area Under Plasma Concentration-Time Curve (AUC) Over the Dosing Interval (AUC0-τ)
Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
AUC From Time of Dosing (t=0h) to the Time of the Last Quantifiable Concentration (AUC0-t)
Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
Total AUC Extrapolated to Infinity (AUC0-∞)
Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
Percentage of AUC0-∞ Due to Extrapolation From the Time of the Last Quantifiable Concentration (Tlast) to Infinity (%AUCextrap)
Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
Apparent Terminal Elimination Rate Constant (λz)
Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
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Apparent Terminal Elimination Half-Life (t1/2)
Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
Apparent Clearance (CL/F)
Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
Apparent Volume of Distribution (V/F)
Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
Pre-dose Plasma Concentration (Ctrough) for Dose 1, Dose 2 and Dose 3
Time frame: Days 5 to 8 (Period 3): pre-dose
Cmax for Dose 1, Dose 2 and Dose 3
Time frame: Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
Tmax for Dose 1, Dose 2 and Dose 3
Time frame: Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
AUC0-τ for Dose 1, Dose 2 and Dose 3
τ=5 h for Dose 1 and Dose 2 and τ=24 h for Dose 3
Time frame: Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
Concentration Over the Dosing Interval (Cτ) for Dose 1, Dose 2 and Dose 3
τ=5 h for Dose 1 and Dose 2 and τ=24 h for Dose 3
Time frame: Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
Apparent Terminal Elimination Half-Life Interval (t1/2) post Dose 3
Time frame: Day 8 (Period 3): up to 24 hours post-dose 3
Ratio of Cmax (R[Cmax])
Accumulation of cytisinicline following TID administration will be assessed by estimating R(Cmax), where R is the ratio of the pharmacokinetic parameter following administration of Dose 1 on Day 8 vs. single-dose administration under fasting conditions during Period 1 or 2.
Time frame: Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)
Ratio of AUC0-τ (R[AUC0-τ])
Accumulation of cytisinicline following TID administration will be assessed by estimating R(AUC0-τ), where R is the ratio of the pharmacokinetic parameter following administration of Dose 1 on Day 8 vs. single-dose administration under fasting conditions during Period 1 or 2.
Time frame: Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)
R(AUC0-τ/AUC0-∞)
Time invariance will be assessed as R(AUC0-τ/AUC0-∞), where AUC0-τ is estimated on Day 8 Dose 1 and AUC0-∞ is estimated for the single-dose under fasting conditions during Period 1 or 2.
Time frame: Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)
Time to Steady State
Time to steady state will be assessed by visual inspection of the Ctrough versus time plot.
Time frame: Days 5 to 8 (Period 3): pre-dose
Number of Participants With Treatment Emergent Adverse Events (AEs)
Time frame: From first dose of study drug through the End-of Study Visit (Day 28-31)
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)
Time frame: Baseline through Day 9
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Time frame: Baseline through Day 9
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests
Time frame: Baseline through Day 9