A Study in Healthy Volunteers to Investigate the Effect of Food on the Bioavailability of Cytisine

NCT03268343 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: ACH-CYT-012017-001562-19
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Smoking Cessation

Outcome Measures

Primary Outcomes (2)

• Plasma Cytisine Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)

  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-∞)

  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)

Secondary Outcomes (8)

• Plasma Cytisine PK: Time of Occurrence of Cmax (Tmax)

  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)

  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%)

  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)

  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 Half-Life (t1/2)

  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)

Study Arms (2)

Schedule A: Fed Then Fasted

EXPERIMENTAL

Schedule A (12 subjects): * 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).

Drug: Cytisine

Schedule B: Fasted Then Fed

EXPERIMENTAL

Schedule B (12 subjects): * 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).

Drug: Cytisine

Interventions

Cytisine DRUG

Cytisine 1.5 mg Film-Coated Tablets

Also known as: Tabex

Schedule A: Fed Then Fasted; Schedule B: Fasted Then Fed

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 investigational medicinal product (IMP).
• 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 IMP.
• Subject with a body mass index (BMI) of 18-32 kg/m\^2. BMI = body weight in kg / \[height in m\]\^2.
• Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days before the first dose of IMP.
• 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).
• Subject with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results.
• 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.
• 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.
• Subject must be available to complete the study (including post study follow-up) and comply with study restrictions.
• Subject must provide written informed consent to participate in the study.

You may not qualify if:

• Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or any of the excipients in the Tabex formulation (lactose, 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).
• Difficulty in donating blood on either arm or known history.
• History of alcoholism or drug abuse within last 2 years.
• 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.
• 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.
• 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.
• 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.
• 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.
• Any inability or difficulty in fasting.
• Inability to communicate well with Investigators (i.e., language problem, poor mental development or impaired cerebral function).
• Any other condition that the Principal Investigator considers making the subject unsuitable for this study.

Sponsors & Collaborators

• Achieve Life Sciences: lead

Study Sites (1)

Simbec Research Ltd

Merthyr Tydfil, CF11 9AB, United Kingdom

Location

MeSH Terms

Conditions

Smoking Cessation

Interventions

cytisine

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Results Point of Contact

• Title: Daniel Cain, Senior Director Clinical Research
• Organization: Achieve Life Sciences

dcain@achievelifesciences.com

425.686.1546

Study Officials

• Annelize Koch, MD

  Simbec Research Ltd (Simbec)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2017
• First Posted: August 31, 2017
• Study Start: August 8, 2017
• Primary Completion: August 26, 2017
• Study Completion: September 1, 2017
• Last Updated: February 26, 2019
• Results First Posted: February 7, 2019

Record last verified: 2019-02

Locations

GB (1)