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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Achieve Life Sciences Inc.

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

8 Aug 2023 → 21 Sep 2023

Decision date (initial)

2023-07-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Achieve Life Sciences, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

To assess the effect of food on the bioavailability of 3 mg cytisinicline following single-dose administration.

Secondary objectives 2

1. To evaluate the pharmacokinetic (PK) profile of 3 mg cytisinicline TID following multiple days of administration during Days 5-8.
2. To assess the safety and tolerability of cytisinicline.

Conditions and MedDRA coding

No medical condition

Study design 1 period

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Free written informed consent prior to any procedure required by the study.
2. Willingness to accept and comply with all study procedures and restrictions.
3. Male or female subject ≥18 years, at the date of signing the informed consent.
4. Regular moderate combustible cigarette smokers (self-reported average of at least 10 cigarettes per day).
5. Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive.
6. Healthy subject, based on medical history, physical examination, vital signs, ECG and clinical laboratory tests.
7. 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).
8. A female subject is eligible if she also meets one of the following criteria: a. 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 b. 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 23

1. Known hypersensitivity/allergic reaction to cytisinicline or any of the excipients.
2. Known severe hypersensitivity reaction to any other drug.
3. 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.
4. Stroke or acute myocardial infarction within the previous 3 months.
5. History of hyperthyroidism.
6. History of psychosis or of a psychotic event.
7. Estimated renal creatinine clearance (CLCr) below the lower limit of the normal range (ie, 90-120 mL/min/1.73 m2 for males and 80-110 mL/min/1.73 m2 for females), based on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to an average body surface area of 1.73 m2.
8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limit of the normal (ULN) range.
9. Positive result in urine drugs-of-abuse or ethanol tests at Screening.
10. Excessive caffeine consumption, defined as ≥800 mg per day.
11. 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).
12. Participation in any clinical trial within the previous 2 months.
13. Use of any smoking cessation medications such as cytisinicline, bupropion, varenicline, nortriptyline, or any NRT (eg, nicotine patch, nicotine chewing gum, or electronic cigarettes) in the previous 8 weeks.
14. Participation in more than 2 clinical trials within the previous 12 months.
15. Blood donation or significant blood loss (≥ 450 mL) due to any reason or had plasmapheresis within the previous 2 months.
16. Female subjects who are lactating or pregnant by serum pregnancy test.
17. Any other condition that the investigator considers the subject to be unsuitable for the study.
18. 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 timeframe in which may interfere with the pharmacokinetics of study drug.
19. 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.
20. 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.
21. Positive result in drugs-of-abuse or ethanol tests.
22. If female, positive pregnancy test in urine.
23. Any other condition that the investigator considers to render the subject unsuitable for the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Cmax, Tlag, Tmax, Tlast, AUC0-τ, AUC0-t, AUC0–∞, %AUCextrap, λz, t1/2, CL/F and V/F
2. Cytisinicline Cmax, AUC0-t, and AUC0–∞ geometric least squares mean ratios for fed vs. fasted

Secondary endpoints 3

1. Days 5-7 (Multiple Dose PK parameters): Ctrough (C5h for Dose 1 and Dose 2, C14h for Dose 3)
2. Day 8 (Multiple Dose PK parameters): For Dose 1, Dose 2 and Dose 3: Cmax, Tmax, AUC0-τ (where τ=5 h for Dose 1 and Dose 2 and τ=14 h for Dose 3), and Ctrough (C5h for Dose 1 and Dose 2, t1/2 for Dose 3 on Day 8 and C14h for Dose 3 collected on Day 9); Accumulation: R(Cmax), R(AUC0-τ); Time Invariance: R(AUC0-τ/AUC0–∞); Time to steady state
3. Adverse events (AEs), electrocardiogram (ECG), vital signs, and clinical laboratory tests

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Achieve Life Sciences Inc.

Sponsor organisation

Achieve Life Sciences Inc.

Address

22722 29th Drive Southeast Ste 100

City

Bothell

Postcode

98021-4420

Country

United States

Scientific contact point

Organisation

Achieve Life Sciences Inc.

Contact name

Daniel Cain

Public contact point

Organisation

Achieve Life Sciences Inc.

Contact name

Daniel Cain

Third parties 4

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications