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Smoking CessationPhase 1NCT05566288

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

A Phase 1 study testing Cytisinicline and Moxifloxacin in people with Smoking Cessation, run by Achieve Life Sciences at 1 site in Portugal.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Smoking Cessation
What is being tested?
Cytisinicline and Moxifloxacin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
27 participants
Where
1 sitePortugal
Study dates
17 Oct 2022to 23 Dec 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Subjects must meet ALL of the following criteria to be eligible for inclusion into the study:
  • 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.
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  • 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.

Who cannot join

  • Subjects meeting ANY of the following exclusion criteria will NOT be eligible for inclusion into the study.
  • 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.
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  • 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
  • Second or third-degree atrioventricular (AV) block
  • Any rhythm other than sinus rhythm, which is interpreted by the investigator to be clinically significant
  • Renal impairment defined as a creatinine clearance (CrCl) <90 mL/min, based on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to an average surface area of 1.73 m2, at Screening.
  • Serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) above the ULN (upper limit of the reference range at Screening).
  • Positive urine drug and alcohol screen at Screening or Day -1 for each Treatment Period.
  • Positive pregnancy test for women of child-bearing potential (WOCBP) at Screening or Day-1 to each Treatment Period.
  • History of significant alcohol abuse, drug abuse, or use of illicit drugs within one year prior to Screening.
  • Average weekly alcohol consumption of >14 units for males and >7 units for females within the previous 6 months.
  • Average daily consumption of methylxanthines-containing beverages or food (e.g., coffee, tea, cola, sodas, chocolate) equivalent to >500 mg of methylxanthines.
  • Subject has donated or lost ≥450 mL of blood within the previous 2 months prior to study drug administration or has donated plasma within 7 days prior to study drug administration.
  • Known hypersensitivity/allergy reaction to moxifloxacin or other fluoroquinolones.
  • Use of prescription medication within 14 days or 5 half-lives (whichever is longer) or over-the-counter products (including natural food supplements) within 7 days prior to admission to Treatment Period 1, unless in the investigator's opinion the medication does not interfere with the pharmacokinetics of study drug or compromise subject safety. Exceptions include topical products without systemic absorption, hormonal contraceptives, hormone replacement therapy, and acetaminophen (≤2 g/day).
  • Any allergy, intolerance, restriction or special diet that, in the opinion of the investigator, could contraindicate the subject's participation in this study.
  • History of unexplained loss of consciousness, unexplained syncope, unexplained irregular heartbeats or palpitations or near drowning with hospital admission.
  • Subjects who received any investigational drug 30 days or 5 half-lives (whichever is longer) prior to first study drug administration.
  • Use of other forms of nicotine (e-cigarettes, smokeless tobacco) or are planning to use these products during study.
  • Known hypersensitivity/allergy reaction to varenicline, cytisinicline or other cytisinicline-derivatives.
  • Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test, prior to admission to each study period.
  • Any reason which, in the opinion of the investigator, would prevent the subject from participating in the study.

Trial locations and contacts

1 site in 1 country.

Portugal1 site
  • BlueClinical Phase I

    Porto, 4250-449

Other trials in Portugal

About this study

Official title: A Four Way Crossover Thorough QT/QTc Study to Evaluate the Electrocardiographic Effects of Therapeutic and Supratherapeutic Doses of Cytisinicline in Healthy Smokers

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.

Being tested
Cytisinicline, Placebo, Moxifloxacin
Medical subject headings
Smoking Cessation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CytisiniclineDrug

    Also called Cytisine

    compressed film-coated tablet containing 3 mg cytisinicline

  • PlaceboDrug

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

  • MoxifloxacinDrug

    400 mg tablets

Study groups in NCT05566288
Study groupRoleWhat they receive
Sequence 1ExperimentalParticipants 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.
Receives: Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin
Sequence 2ExperimentalParticipants 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.
Receives: Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin
Sequence 3ExperimentalParticipants 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.
Receives: Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin
Sequence 4ExperimentalParticipants 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.
Receives: Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin
Sequence 5ExperimentalParticipants 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.
Receives: Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin
Sequence 6ExperimentalParticipants 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.
Receives: Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin
Sequence 7ExperimentalParticipants 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.
Receives: Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin
Sequence 8ExperimentalParticipants 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.
Receives: Drug: Cytisinicline; Drug: Placebo; Drug: Moxifloxacin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: 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.

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

    Measured: 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.

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

    Measured: 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.

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

    Measured: 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.

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

    Measured: 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.

  6. Predicted Placebo-Adjusted Change From Baseline in PR (ΔΔPR)

    Measured: 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.

  7. Predicted Placebo-Adjusted Change From Baseline in QRS Duration (ΔΔQRS)

    Measured: 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.

  8. Percentage of Participants With New Onset (Post-Baseline) Findings on ECG Morphology

    Measured: 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.

  9. Uncorrected Change From Baseline Over Time in QT Interval of the Electrocardiogram (QT)

    Measured: 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.

  10. Uncorrected Change From Baseline Over Time in PR

    Measured: 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.

  11. Uncorrected Change From Baseline Over Time in QRS

    Measured: 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.

  12. Uncorrected Change From Baseline Over Time in HR

    Measured: 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.

  13. Percentage of Participants Meeting Outlier Criteria Based on Uncorrected QT, PR, QRS, and HR Values

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Oct 2022
  2. Study start17 Oct 2022
  3. Primary completion23 Dec 2022
  4. Study completion23 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05566288
Sponsor's protocol ID
ACH-CYT-06
Status last verified
May 2023
First submitted
30 Sep 2022
Last updated
18 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cytisinicline and Moxifloxacin in people with Smoking Cessation, run by Achieve Life Sciences at 1 site in Portugal.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Predicted Placebo-Adjusted Change From Baseline in the Corrected QT Interval using Fridericia's Formula (QTcF) Interval (ΔΔQTcF) (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2023.

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