A Four Way Crossover Thorough QT/QTc Study to Evaluate the Electrocardiographic Effects of Therapeutic and Supratherapeutic Doses of Cytisinicline in Healthy Smokers
- Trial ID
- 2022-500954-40-00
- Protocol
- ACH-CYT-06
- Sponsor
- Achieve Life Sciences Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **electrocardiographic** effects of both therapeutic and supratherapeutic doses of Cytisinicline in healthy smokers. This is clinically relevant as it aims to assess the cardiac safety profile of Cytisinicline, a treatment for **nicotine addiction**, by determining its impact on the QT/QTc interval, which is a critical measure of cardiac repolarization and potential arrhythmogenic risk.
Participants
The clinical trial focuses on individuals with **nicotine addiction**. The study population includes both male and female participants, with an age range categorized as adults. The trial involves a vulnerable population, although specific details regarding the total number of participants have not been provided by the sponsor. Participants were selected based on criteria that are not disclosed in the available data. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not provided information on key inclusion or exclusion criteria for this study.
Plans and Procedures
The clinical trial is designed to evaluate the **electrocardiographic** effects of therapeutic and supratherapeutic doses of Cytisinicline in individuals with **nicotine addiction**. This study is structured as a four-way crossover trial, which is a randomized, double-blind, and controlled design. The trial is set to commence recruitment on October 29, 2022, and is estimated to conclude by November 23, 2022. Participants will be involved in the study for the duration of the trial, which spans approximately one month.
The sequence of study visits begins with an inclusion visit, also known as the screening visit, where potential participants are assessed for eligibility based on predefined criteria. Following successful screening, participants will undergo a series of study visits where they will receive either therapeutic or supratherapeutic doses of Cytisinicline, with each treatment period separated by a washout phase to prevent carryover effects. The purpose of these visits is to monitor the **QT/QTc interval** on an electrocardiogram, ensuring the safety and efficacy of the drug at varying doses.
Throughout the trial, follow-up visits will be conducted to assess the ongoing health and safety of the participants, as well as to collect data on the primary and secondary endpoints. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be made, and any remaining data will be collected. Participants may be subject to early termination from the study if they experience adverse effects, fail to comply with study protocols, or withdraw consent. The trial is conducted in accordance with Phase 3 clinical trial standards, ensuring rigorous evaluation of the investigational product's safety and efficacy in the target population.
Treatment
The clinical trial documentation does not provide specific details regarding the **experimental medication** used in the study. Information such as the name, pharmaceutical form, dosage, route, and frequency of administration is not available. Additionally, there is no data on whether the medication is a **paediatric formulation** or if it is classified as an **orphan drug**. The maximum daily dose, total dose, and treatment period are also unspecified.
Details about any **non-experimental treatments** used in the study, such as standard-of-care therapy, placebo, or comparator treatment, are not provided. There is no information on additional relevant aspects of drug administration, dosing schedules, or participant compliance monitoring. The absence of these details limits the ability to describe the treatment regimen comprehensively.
Efficacy
The clinical trial is in Phase 3, which typically involves assessing the efficacy of a treatment in a larger patient population. However, specific parameters or endpoints used to evaluate efficacy, such as symptom improvement scores, biomarker levels, or disease remission rates, are not provided. The methods and schedule for measuring, collecting, and analyzing these efficacy parameters, including any tools or instruments involved, are also not detailed in the available data. The trial's estimated recruitment start date was October 29, 2022, with an estimated end date of November 23, 2022. Further information regarding the efficacy assessment is not available in the provided data.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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: a. is of non-childbearing potential or b. is of childbearing potential and agrees to use an accepted contraceptive method 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.
Exclusion Criteria
- 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: a. QTcF >450 ms b. QRS >110 ms c. PR >200 ms d. Second or third-degree AV block e. 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 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 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 Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Portugal | Not Recruiting | 29 Oct 2022 | 32 |
Sites & Investigators
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Cytisinicline Placebo | Placebo | N/A | — | — | — | N/A |
Avelox 400 mg comprimidos revestidos por película | Comparator | COMPRIMIDOS REVESTIDOS POR PELÍCULA | ORAL USE | 400 | 1 | PRD3666125 |
Cytisinicline | Test | FILM COATED TABLETS | ORAL | 24 | 2 | PRD9785973 |