A Phase 1 Open Label, Randomized, Two-Way Crossover Study in Healthy Smokers to Investigate the Effect of Food on the Bioavailability of Cytisine in a New Formulation

Achieve Life Sciences1 site in 1 country13 target enrollmentApril 27, 2018

ConditionsSmoking Cessation

Interventionscytisine

Drugscytisine

Overview

Phase: Phase 1
Intervention: cytisine
Conditions: Smoking Cessation
Sponsor: Achieve Life Sciences
Enrollment: 13
Locations: 1
Primary Endpoint: Maximum Concentration (Cmax)
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This will be an open-label, randomised, 2-treatment period, single-dose crossover study to determine the comparative bioavailability and renal elimination following single-dose administration of 3.0 mg cytisine in healthy smokers under fed and fasted conditions.

Registry

clinicaltrials.gov

Start Date

April 27, 2018

End Date

June 12, 2018

Last Updated

6 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

Achieve Life Sciences

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•To be Confirmed at Screening
•Subject is current cigarette smoker.
•Healthy males and females between 18 and 55 years of age.
•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.
•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.
•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.
•Subject with a body mass index (BMI) of 23-28 kg/m\^
•BMI = body weight in kg / \[height in m\^2\].
•Subject with no clinically significant abnormal serum biochemistry or haematology values within 28 days before the first dose of cytisine.
•Subject with negative urinary drugs of abuse screen, determined within 28 days before the first dose of cytisine (a positive result may be repeated at Investigator's discretion).

Exclusion Criteria

•To be Confirmed at Screening
•Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or any of the excipients in the Tabex formulation (cellulose, talc, magnesium).
•History of severe hypersensitivity reactions to any other drugs.
•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).
•Female subjects who are breast feeding.
•Difficulty in donating blood on either arm or known history.
•History of alcoholism or drug abuse within last 2 years.
•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 cytisine dose, unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise subject safety.
•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
•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 cytisine dose.

Arms & Interventions

Schedule A: Fed Then Fasted

Schedule A (6 participants): * Period 1: cytisine (2 x 1.5 mg tablets) will be administered 30 minutes after the start of a high fat breakfast (fed state) * Period 2: cytisine (2 x 1.5 mg tablets) will be administered after an overnight fast of at least 10 hours (fasting state)

Intervention: cytisine

Schedule B: Fasted Then Fed

Schedule B (6 participants): * Period 1: cytisine (2 x 1.5 mg tablets) will be administered after an overnight fast of at least 10 hours (fasting state) * Period 2: cytisine (2 x 1.5 mg tablets) will be administered 30 minutes after the start of a high fat breakfast (fed state)

Intervention: cytisine

Outcomes

Primary Outcomes

Maximum Concentration (Cmax)

Time Frame: Pre-dose (within 60 minutes prior to dosing), up to 48 hours post-dose on Days 1-5

Area Under the Concentration Versus Time Curve (AUC) Extrapolated to Infinity (AUC0-∞)

Time Frame: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5

Total Cytisine Excreted in Urine Over 48 Hours (Ae0-48h)

Time Frame: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5

Percent of Total Cytisine Excreted in Urine Over 48 Hours (Ae0-48h%)

Time Frame: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5

Secondary Outcomes

Time to Cmax (Tmax)(Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5)
Terminal Elimination Half-Life (T1/2)(Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5)
AUC From Time of Dosing to Last Measurable Concentration (AUC0-t)(Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5)
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Withdrawal of Study Drug(Baseline (Day 0) through Day 5 plus 6-8 days)
Number of Participants With Clinically Significant Biochemistry, Hematology, Urinalysis, and/or 12-lead Electrocardiogram (ECG) Values(Screening through Day 5)