A Single Dose-escalation Study of Cytisine in Adult Smokers

NCT03848208 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: ACH-CYT-082018-003344-22
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

The objectives of this study are:

1. 1.To assess the tolerability and safety of cytisine as a single oral dose.
2. 2.To define the Cmax levels associated to the occurrence of dose-limiting adverse events.

Conditions

Smoking Cessation

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation

  An adverse event (AE) is defined as any untoward medical occurrence that does not necessarily have to have a causal relationship with the treatment. A serious AE is any untoward medical occurrence or effect, that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; or is an important medical event which requires medical intervention to prevent one of the above. Treatment emergent events are those that occurred after the first dose of study drug.

  From first dose of study drug through Day 6

• Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)

  Day 1: Pre-dose (within 30 minutes prior to dosing), 15, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours (+/-2 minutes) post-dose

• Pharmacokinetics: Time to Occurrence of Cmax (Tmax)

  Day 1: Pre-dose (within 30 minutes prior to dosing), 15, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours (+/-2 minutes) post-dose

Study Arms (18)

Cohort 1: Cytisine 6.0 mg

EXPERIMENTAL

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: cytisine

Cohort 1: Placebo

PLACEBO COMPARATOR

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: placebo

Cohort 2: Cytisine 9.0 mg

EXPERIMENTAL

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: cytisine

Cohort 2: Placebo

PLACEBO COMPARATOR

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: placebo

Cohort 3: Cytisine 12.0 mg

EXPERIMENTAL

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: cytisine

Cohort 3: Placebo

PLACEBO COMPARATOR

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: placebo

Cohort 4: Cytisine 15.0 mg

EXPERIMENTAL

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: cytisine

Cohort 4: Placebo

PLACEBO COMPARATOR

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: placebo

Cohort 5: Cytisine 18.0 mg

EXPERIMENTAL

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: cytisine

Cohort 5: Placebo

PLACEBO COMPARATOR

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: placebo

Cohort 6: Cytisine 21.0 mg

EXPERIMENTAL

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: cytisine

Cohort 6: Placebo

PLACEBO COMPARATOR

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: placebo

Cohort 7: Cytisine 24.0 mg

EXPERIMENTAL

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: cytisine

Cohort 7: Placebo

PLACEBO COMPARATOR

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: placebo

Cohort 8: Cytisine 27.0 mg

EXPERIMENTAL

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: cytisine

Cohort 8: Placebo

PLACEBO COMPARATOR

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: placebo

Cohort 9: Cytisine 30.0 mg

EXPERIMENTAL

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: cytisine

Cohort 9: Placebo

PLACEBO COMPARATOR

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Drug: placebo

Interventions

cytisine DRUG

cytisine film-coated oral tablet

Also known as: Tabex, cytisinicline

Cohort 1: Cytisine 6.0 mg; Cohort 2: Cytisine 9.0 mg; Cohort 3: Cytisine 12.0 mg; Cohort 4: Cytisine 15.0 mg; Cohort 5: Cytisine 18.0 mg; Cohort 6: Cytisine 21.0 mg; Cohort 7: Cytisine 24.0 mg; Cohort 8: Cytisine 27.0 mg; Cohort 9: Cytisine 30.0 mg

placebo DRUG

matching placebo oral tablet

Cohort 1: Placebo; Cohort 2: Placebo; Cohort 3: Placebo; Cohort 4: Placebo; Cohort 5: Placebo; Cohort 6: Placebo; Cohort 7: Placebo; Cohort 8: Placebo; Cohort 9: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Free written informed consent prior to any procedure required by the study.
• Male or female subjects, age ≥18 years, at the time of signing the informed consent.
• Current daily cigarette smokers (averaging at least 10 cigarettes per day in the past 30 days).
• Expired air carbon monoxide (CO) ≥10 ppm.
• Able to swallow multiple tablets at one time.
• Able to fully understand, comply with all study requirements.

You may not qualify if:

• Known hypersensitivity to cytisine or any of the excipients.
• Known severe hypersensitivity to any other drug.
• Positive urinary drugs of abuse screen, determined within 28 days before cytisine/placebo dosing.
• Positive ethanol breath test.
• Clinically significant abnormal serum chemistry, hematology, coagulation or urinalysis values within 28 days of randomization (i.e. requiring treatment or monitoring).
• Clinically significant abnormalities in 12-lead echocardiogram (ECG) determined after minimum of 5 minutes in supine position within 28 days of randomization (i.e. requiring treatment or further assessment).
• Body Mass Index (BMI) classification for being underweight (\<18.5 kg/m2) or having ≥Class 2 obesity (≥35 kg/m2).
• History of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident, cardiac arrhythmia, or hospitalization for congestive heart failure.
• Blood pressure ≥160/100 mmHg, measured on the dominant arm, after at least 3 minutes in supine position.
• Creatinine clearance (CrCl) \<80 mL/min (estimated with the Cockroft-Gault equation).
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.0 x the upper limit of normal (ULN).
• Any inability to comply with study restrictions (See Section 9)
• Any inability or difficulty in fasting.
• Difficulty in donating blood on either arm.
• If woman of childbearing potential, positive result in serum beta-human chorionic gonadotropin (hCG) pregnancy test.

Sponsors & Collaborators

• Achieve Life Sciences: lead

Study Sites (1)

BlueClinical

Porto, 4250-449, Portugal

Location

MeSH Terms

Conditions

Smoking Cessation

Interventions

cytisine

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Results Point of Contact

• Title: Daniel Cain, Vice President, Clinical Research
• Organization: Achieve Life Sciences

dcain@achievelifesciences.com

425.686.1546

Study Officials

• Marlene Fonseca, MD

  Hospital da Prelada

  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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: February 20, 2019
• Study Start: February 28, 2019
• Primary Completion: September 12, 2019
• Study Completion: September 12, 2019
• Last Updated: September 17, 2020
• Results First Posted: September 17, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)