Study to Evaluate Electrocardiographic Effects of Therapeutic & Supratherapeutic Doses of Cytisinicline in Healthy Smokers

NCT05566288 | Completed Phase 1 FDA Drug

• 1 other identifier: ACH-CYT-06
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this trial is to assess the effects of cytisinicline at therapeutic and supratherapeutic doses on cardiac repolarization relative to placebo in healthy adult subjects who are smokers.

Conditions

Smoking Cessation

Outcome Measures

Primary Outcomes (1)

• Predicted Placebo-Adjusted Change From Baseline in the Corrected QT Interval using Fridericia's Formula (QTcF) Interval (ΔΔQTcF)

  Day -1 (first treatment period only) and on Day 1 (the day of dosing during each treatment period) from approximately 1 hour pre-dose on Day 1 through approximately 24 hours post dose on Day 1.

Secondary Outcomes (13)

• Placebo-Adjusted Change From Baseline Over Time in Corrected QT Interval (QTc; Corrected for Heart Rate Based on the ΔΔQTcF)

  Day -1 (first treatment period only) and on Day 1 (the day of dosing during each treatment period) from approximately 1 hour pre-dose on Day 1 through approximately 24 hours post dose on Day 1.

• Placebo-Adjusted Change From Baseline Over Time in Heart Rate (HR)

  Day -1 (first treatment period only) and on Day 1 (the day of dosing during each treatment period) from approximately 1 hour pre-dose on Day 1 through approximately 24 hours post dose on Day 1.

• Placebo-Adjusted Change From Baseline Over Time in PR Interval of the Electrocardiogram (PR)

  Day -1 (first treatment period only) and on Day 1 (the day of dosing during each treatment period) from approximately 1 hour pre-dose on Day 1 through approximately 24 hours post dose on Day 1.

• Placebo-Adjusted Change From Baseline Over Time in QRS Interval of the Electrocardiogram (QRS) Duration

  Day -1 (first treatment period only) and on Day 1 (the day of dosing during each treatment period) from approximately 1 hour pre-dose on Day 1 through approximately 24 hours post dose on Day 1.

• Predicted Placebo-Adjusted Change From Baseline in HR (ΔΔHR)

  Day -1 (first treatment period only) and on Day 1 (the day of dosing during each treatment period) from approximately 1 hour pre-dose on Day 1 through approximately 24 hours post dose on Day 1.

Study Arms (8)

Sequence 1

EXPERIMENTAL

Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) * Placebo (negative control) (8 placebo tablets) * Moxifloxacin 400 mg PO (positive control) (1 tablet) There will be a minimum 5 day washout between dosing periods.

Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin

Sequence 2

EXPERIMENTAL

Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) * Moxifloxacin 400 mg PO (positive control) (1 tablet) * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) * Placebo (negative control) (8 placebo tablets) There will be a minimum 5 day washout between dosing periods.

Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin

Sequence 3

EXPERIMENTAL

Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Placebo (negative control) (8 placebo tablets) * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) * Moxifloxacin 400 mg PO (positive control) (1 tablet) * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) There will be a minimum 5 day washout between dosing periods.

Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin

Sequence 4

EXPERIMENTAL

Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Moxifloxacin 400 mg PO (positive control) (1 tablet) * Placebo (negative control) (8 placebo tablets) * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) There will be a minimum 5 day washout between dosing periods.

Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin

Sequence 5

EXPERIMENTAL

Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) * Placebo (negative control) (8 placebo tablets) * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) * Moxifloxacin 400 mg PO (positive control) (1 tablet) There will be a minimum 5 day washout between dosing periods.

Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin

Sequence 6

EXPERIMENTAL

Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Placebo (negative control) (8 placebo tablets) * Moxifloxacin 400 mg PO (positive control) (1 tablet) * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) There will be a minimum 5 day washout between dosing periods.

Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin

Sequence 7

EXPERIMENTAL

Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) * Moxifloxacin 400 mg PO (positive control) (1 tablet) * Placebo (negative control) (8 placebo tablets) There will be a minimum 5 day washout between dosing periods.

Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin

Sequence 8

EXPERIMENTAL

Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Moxifloxacin 400 mg PO (positive control) (1 tablet) * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) * Placebo (negative control) (8 placebo tablets) * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) There will be a minimum 5 day washout between dosing periods.

Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin

Interventions

Cytisinicline DRUG

compressed film-coated tablet containing 3 mg cytisinicline

Also known as: Cytisine

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6; Sequence 7; Sequence 8

Placebo DRUG

Placebo tablets to match compressed film-coated tablet containing 3 mg cytisinicline

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6; Sequence 7; Sequence 8

Moxifloxacin DRUG

400 mg tablets

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6; Sequence 7; Sequence 8

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Regular moderate cigarette smokers (minimum 10 cigarettes per day).
• Healthy males and females 18-45 years of age.
• If woman, she meets one of the following criteria:
• is of non-childbearing potential (refer to Section 8.3-Contraception Requirements for the criteria for non-childbearing potential status); or
• is of childbearing potential and agrees to use an accepted contraceptive method (refer to Section 8.3-Contraception Requirements for a list of accepted methods) from at least 4 weeks prior to admission to period 1 until at least the last study drug administration.
• No clinically significant abnormal serum chemistry or hematology values at Screening.
• Body mass index (BMI) within 18-30 kg/m2 at Screening.
• Subject must be willing to communicate with the investigator and site staff and comply with all study procedures and requirements.
• Subject must be able to provide written, informed consent including compliance with the requirements listed in the consent form.
• Subject must be able and willing to swallow whole tablets without breaking, cutting, or chewing.

You may not qualify if:

• History or presence of a systemic disease, which as judged by the investigator, may affect the subject's ability to participate in the study or in the outcome of the study.
• Evidence of infection with Hepatitis B or C, or human immunodeficiency virus HIV-1 or HIV-2, as determined by results of testing at Screening.
• Female subjects who are pregnant or lactating.
• Family history of QTc prolongation or of unexplainable sudden death at \<50 years of age.
• History of QTc prolongation or knowledge of any kind of cardiovascular disorder/condition known to increase the possibility of QT prolongation or history of additional risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome or Brugada Syndrome) or cardiac conduction disorders.
• History of myocardial infarction, unstable angina pectoris, cerebrovascular disease, atherosclerosis or arterial hypertension.
• History of rare hereditary problem of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
• History of glucose 6-phosphate dehydrogenase deficiency or myasthenia gravis.
• Use of any medication that might interfere with the PK of cytisinicline.
• Resting supine pulse rate less than 50 beats per minute or greater than 100 beats per minute at Screening.
• Resting supine systolic blood pressure less than 90 mmHg or greater than 140 mmHg; resting supine diastolic blood pressure less than 50 mmHg or greater than 90 mmHg at Screening.
• Clinically significant ECG abnormalities at Screening, including:
• QTcF \>450 ms
• QRS \>110 ms
• PR \>200 ms

Sponsors & Collaborators

• Achieve Life Sciences: lead

Study Sites (1)

BlueClinical Phase I

Porto, 4250-449, Portugal

Location

MeSH Terms

Conditions

Smoking Cessation

Interventions

cytisine; Moxifloxacin

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Marlene Fonseca, MD

  Blueclinical, Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only the moxifloxacin treatment will not be blinded to site personnel and the participants, but moxifloxacin treatment will be blinded to the central cardiologist for assessments.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2022
• First Posted: October 4, 2022
• Study Start: October 17, 2022
• Primary Completion: December 23, 2022
• Study Completion: December 23, 2022
• Last Updated: May 18, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)