Evaluation of Renal Impairment and Dialysis on Pharmacokinetics of Single 3 mg Cytisinicline Dose in Nicotine Addiction Patients
- Trial ID
- 2022-500921-34-00
- Protocol
- ACH-CYT-05
- Sponsor
- Achieve Life Sciences Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **renal impairment** and **dialysis treatment** on the pharmacokinetics of a single 3 mg dose of **cytisinicline**. This investigation is clinically relevant as it aims to understand how varying levels of kidney function may alter the absorption, distribution, metabolism, and excretion of cytisinicline, a medication used in the treatment of **nicotine addiction**. Understanding these pharmacokinetic changes is crucial for optimizing dosing regimens and ensuring safe and effective use of cytisinicline in patients with compromised renal function.
Participants
The clinical trial focuses on individuals with **nicotine addiction**. The study population includes both male and female participants, encompassing a broad age range from adolescents to adults. The trial involves a vulnerable population, although the specific number of participants has not been disclosed by the sponsor. Participants were selected based on criteria that are not specified in the available data. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the provided information. The trial does not specify any key inclusion or exclusion criteria, and the main objective of the study is not provided.
Plans and Procedures
The clinical trial is designed as a **Phase I, open-label** study to assess the impact of renal impairment and dialysis treatment on the pharmacokinetics of a single 3 mg dose of cytisinicline in individuals with **nicotine addiction**. The trial is expected to commence recruitment on October 4, 2022, and conclude by March 31, 2023. Participants will be involved in the study for a duration that aligns with the trial's timeline, with specific visit schedules and procedures outlined to ensure comprehensive data collection and participant safety.
The study will begin with an inclusion visit, where potential participants will undergo a screening process to determine eligibility based on predefined criteria. This visit will include assessments such as medical history review, physical examination, and laboratory tests. Following successful screening, participants will receive the investigational product and undergo a series of follow-up visits. These visits are structured to monitor the pharmacokinetic profile of cytisinicline, assess safety parameters, and document any adverse events. The end-of-study visit will mark the completion of the participant's involvement, where final evaluations will be conducted to gather concluding data.
Participants are expected to adhere to the study schedule and protocol requirements throughout their involvement. Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or the occurrence of adverse events that compromise participant safety. The trial's open-label design allows for direct observation of the effects of the investigational product, providing valuable insights into its pharmacokinetics in the context of renal impairment and dialysis treatment.
Treatment
No specific information regarding the experimental medication, including its name, pharmaceutical form, dosage, route, and frequency of administration, is provided in the available data. Consequently, a detailed description of the experimental treatment cannot be formulated based on the current dataset.
Similarly, there is no information available about any non-experimental treatments used in the study, such as standard-of-care therapy, placebo, or comparator treatment. Therefore, a description of these elements is not possible with the given data.
Additional relevant information about drug administration, dosing schedules, and participant compliance monitoring is also absent from the provided dataset. As such, no further details can be included in this description.
Efficacy
The clinical trial is designed to assess efficacy in a Phase 3 study. The trial is scheduled to begin recruitment on October 4, 2022, with an estimated end date of March 31, 2023. The efficacy of the investigational treatment will be evaluated using specific parameters or endpoints, although these are not detailed in the provided data. The trial will follow a structured methodology to measure, collect, and analyze these efficacy parameters at predetermined timepoints throughout the study duration. The trial's design and execution will adhere to rigorous standards to ensure the reliability and validity of the efficacy assessments. The results will contribute to understanding the treatment's potential benefits and inform future clinical decisions.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Free written informed consent prior to any procedure required by the study.
- Ability to communicate well with the investigator, in a language understandable to the subject, and to understand and comply with the requirements of the study.
- Willingness to accept and comply with all study procedures and restrictions.
- Male or female subject between 18 and 75 years, inclusive, at Screening.
- Body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive, at Screening.
- A female subject is eligible if she meets one of the following criteria: a. is of non-childbearing potential (underwent a permanent sterilization method [e.g., hysterectomy, bilateral salpingectomy and 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 28 days prior to dose administration (prior to first dose administration for Group 5) until at least 1 month after the end of study (EOS).
- 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).
- Stable concomitant medications for at least 7 days prior to dose administration (first dose administration for Group 5) and up to the EOS.
- eGFR at Screening within: • 60-89 mL/min for Group 2 (mild renal impairment subjects). • 30-59 mL/min for Group 3 (moderate renal impairment subjects). • 15-29 mL/min for Group 4 (severe renal impairment subjects). • <15 mL/min for Group 5 (ESRD subjects) determined by the Cockcroft-Gault equation
- Subjects with ESRD are on dialysis for at least 3 months prior to Screening
- Systolic blood pressure (SBP) 100-180 mmHg, diastolic blood pressure (DBP) 50-105 mmHg, and pulse rate 50–100 bpm (inclusive), at Screening and Admission.
- eGFR ≥90 mL/min at Screening, determined by the Cockcroft-Gault equation.
- No clinically relevant abnormalities on clinical laboratory tests at Screening.
- Blood pressure and pulse rate at Screening within the following ranges: • SBP 90-140 mmHg, DBP 60-90mmHg, and pulse rate 60-100 bpm (inclusive) for subjects <65 years of age. • SBP 95-160mmHg, DBP 65-–95 mmHg, and pulse rate 60-100 bpm (inclusive) for subjects ≥65 years of age.
Exclusion Criteria
- Known hypersensitivity/allergy reaction to cytisinicline substance or any of the excipients.
- History of renal, heart, and/or liver transplant.
- History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere in a relevant manner with the absorption, distribution, metabolism, or excretion of the study treatment, except for renal disease.
- Symptoms of an acute clinically relevant infection in the 4-week period preceding Screening (e.g., bacterial, viral, or fungal infection).
- History or clinical evidence of alcohol use disorder or substance use disorder according to DSM-5 classification, within the 3-year period prior to Screening.
- Clinically relevant abnormalities on a 12-lead electrocardiogram (ECG), recorded after 5 min in the supine position at Screening.
- Currently using any creatine supplement.
- Nicotine consumption (e.g., smoking, nicotine patch, nicotine chewing gum, or electronic cigarettes) from 48 hours prior to Admission.
- Excessive caffeine consumption, defined as ≥800 mg per day at Screening.
- Positive result in drugs-of-abuse or ethanol tests at Screening or Admission.
- Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access or puncture; veins with a tendency to rupture during or after puncture).
- Participation in any clinical trial within the previous 2 months.
- Loss of 250 mL or more blood within 3 months prior to screening.
- If female, positive pregnancy test in serum at Screening or positive pregnancy test in urine at Admission.
- If female, she is breast-feeding.
- Presence of severe cardiac disease.
- History of severe renal artery stenosis.
- Presence of unstable diabetes mellitus.
- Acute, ongoing, recurrent, or chronic systemic disease other than renal function impairment that could interfere with the evaluation of the study results.
- Presence of any organ disorder, except for renal function impairment, which might interfere with the PK of cytisinicline.
- Use of any medication which might interfere with the PK of cytisinicline.
- Clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry, and urinalysis), except for those related to renal impairment, at Screening.
- Blood hemoglobin <10g/dL at Screening.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Portugal | Not Recruiting | 04 Oct 2022 | 28 |
 Spain | Not Recruiting | 04 Oct 2022 | 28 |
Sites & 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 | Test | FILM COATED TABLETS | ORAL | 3 | 1 | PRD9785973 |