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Completed

NCT Number: NCT05981768

Study to Evaluate Effect of Food on Bioavailability of Single 3 mg Tablet and Pharmacokinetics (PK) of Multiple 3 mg Doses in Healthy Adult Smokers

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.

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Key information

Conditions

Smoking Cessation Behavior Health Behavior

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

BlueClinical Phase I

Porto, 4250-449, Portugal

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Free written informed consent prior to any procedure required by the study.
  • Willingness to accept and comply with all study procedures and restrictions.
  • Male or female subject ≥ 18 years, at the date of signing the informed consent.
  • Regular moderate combustible cigarette smokers (self-reported average of at least 10 cigarettes per day).
  • Body mass index (BMI) of 18.0 to 30.0 kg/m^2, inclusive.
  • Healthy subject, based on medical history, physical examination, vital signs, ECG and clinical laboratory tests.
  • Negative test results for anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV-1Ab and anti-HIV-2Ab), Hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus antibodies (anti-HCVAb).
  • A female subject is eligible if she also meets one of the following criteria:
  • is of non-childbearing potential (underwent a permanent sterilization method [eg, hysterectomy, bilateral salpingectomy or bilateral oophorectomy], is clinically diagnosed infertile, or is in a post-menopausal state); or
  • is of childbearing potential and agrees to use an accepted contraceptive method from at least 4 weeks prior to admission and until at least 4 weeks after the last dose administration (Day 8).

Exclusion criteria

AT SCREENING

  • Known hypersensitivity/allergic reaction to cytisinicline or any of the excipients.
  • Known severe hypersensitivity reaction to any other drug.
  • Any medical condition (eg, gastrointestinal, renal or hepatic, including peptic ulcer, inflammatory bowel disease or pancreatitis) or surgical condition (eg, cholecystectomy, gastrectomy) that may affect drug pharmacokinetics (absorption, distribution, metabolism or excretion) or subject safety.
  • Stroke or acute myocardial infarction within the previous 3 months.
  • History of hyperthyroidism.
  • History of psychosis or of a psychotic event.
  • Estimated renal creatinine clearance (CLCr) below the lower limit of the normal range (ie, 90-120 mL/min/1.73 m^2 for males and 80-110 mL/min/1.73 m^2 for females), based on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to an average body surface area of 1.73 m^2.
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limit of the normal (ULN) range.
  • Positive result in urine drugs-of-abuse or ethanol tests at Screening.
  • Excessive caffeine consumption, defined as ≥ 800 mg per day.
  • Veins unsuitable for intravenous puncture on either arm (eg, veins that are difficult to locate, access or puncture; veins with a tendency to rupture during or after puncture).
  • Participation in any clinical trial within the previous 2 months.
  • Use of any smoking cessation medications such as cytisinicline, bupropion, varenicline, nortriptyline, or any nicotine replacement therapy (NRT; eg, nicotine patch, nicotine chewing gum, or electronic cigarettes) in the previous 8 weeks.
  • Participation in more than 2 clinical trials within the previous 12 months.
  • Blood donation or significant blood loss (≥ 450 mL) due to any reason or had plasmapheresis within the previous 2 months.
  • Female subjects who are lactating or pregnant by serum pregnancy test.
  • Any other condition that the investigator considers the subject to be unsuitable for the study.

AT ADMISSION

  • Any recent disease or condition or treatment that, according to the investigator, would put the subject at undue risk due to study participation or occurred at a time frame in which may interfere with the pharmacokinetics of study drug.
  • Use of any medicinal products, prescription and non-prescription (including vitamins, food supplements, herbal supplements [including St John's Wort]), in the previous 2 weeks, unless in the investigator's opinion the medication does not interfere with the pharmacokinetics of study drug or compromise subject safety.

NOTE: The use of topical products without systemic absorption, acetaminophen (paracetamol) at doses of ≤ 2 grams/day, and hormonal contraceptives are acceptable.

  • Use of any smoking cessation medications (eg, cytisinicline, bupropion, varenicline, nortriptyline, or any NRT eg, nicotine patch, nicotine chewing gum, or electronic cigarettes) since Screening.
  • Positive result in drugs-of-abuse or ethanol tests.
  • If female, positive pregnancy test in urine.
  • Any other condition that the investigator considers to render the subject unsuitable for the study.

Treatment and study plan

cytisinicline

Drug

film-coated oral tablets containing 3 mg cytisinicline

Other names: Cytisine

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Apparent Clearance (CL/F)

    Time frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose

  12. 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

  13. Pre-dose Plasma Concentration (Ctrough) for Dose 1, Dose 2 and Dose 3

    Time frame: Days 5 to 8 (Period 3): pre-dose

  14. 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)

  15. 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)

  16. AUC0-τ 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)

    τ=5 h for Dose 1 and Dose 2 and τ=24 h for Dose 3

  17. Concentration Over the Dosing Interval (Cτ) 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)

    τ=5 h for Dose 1 and Dose 2 and τ=24 h for Dose 3

  18. Apparent Terminal Elimination Half-Life Interval (t1/2) post Dose 3

    Time frame: Day 8 (Period 3): up to 24 hours post-dose 3

  19. Ratio of Cmax (R[Cmax])

    Time frame: Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)

    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.

  20. Ratio of AUC0-τ (R[AUC0-τ])

    Time frame: Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)

    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.

  21. R(AUC0-τ/AUC0-∞)

    Time frame: Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)

    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.

  22. Time to Steady State

    Time frame: Days 5 to 8 (Period 3): pre-dose

    Time to steady state will be assessed by visual inspection of the Ctrough versus time plot.

  23. 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)

  24. Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)

    Time frame: Baseline through Day 9

  25. Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

    Time frame: Baseline through Day 9

  26. Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests

    Time frame: Baseline through Day 9

Sponsors and collaborators

Lead sponsor

Achieve Life Sciences

Industry

Registry information

Official study title

A Phase 1 Study to Investigate the Effect of Food on the Bioavailability of a Single Cytisinicline 3 mg Tablet and Evaluation of the Pharmacokinetics of Multiple 3 mg Doses (Three Times Daily) in Healthy Adult Smokers

Important dates

Study start
2023
Primary completion
2023
Study completion
2023
First posted
Aug 8, 2023
Registry last updated
Oct 18, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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