A Phase I, Open-Label Study to Evaluate the Effect of Renal Impairment and Dialysis Treatment on the Pharmacokinetics of a Single 3 mg Cytisinicline Dose.

Achieve Life Sciences6 个研究点分布在 2 个国家目标入组 44 人开始时间: 2023年1月10日最近更新: 2025年7月11日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Achieve Life Sciences
入组人数: 44
试验地点: 6
主要终点: Plasma PK Parameter: Fraction Unbound (fu)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The primary objectives of this study are:

To obtain information on the pharmacokinetics of cytisinicline following a single oral dose in subjects with varying degrees of renal impairment relative to matched controls with normal renal function.
To investigate the extent of cytisinicline removal by hemodialysis.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 75 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•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/m^2, inclusive, at Screening.
•A female subject is eligible if she meets one of the following criteria:
•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
•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.
•Additional Inclusion Criteria for Subjects with Renal Impairment (Groups 2 to 5)
•eGFR at Screening, determined by the Cockcroft-Gault equation, 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)
•Subjects with ESRD are on dialysis for at least 3 months prior to Screening.
•Systolic blood pressure (SBP) 100-180mmHg, diastolic blood pressure (DBP) 50-105 mmHg, and pulse rate 50-100 bpm (inclusive), at Screening and Admission.
•Additional Inclusion Criteria for Subjects with Normal Renal Function (Group 1)
•Estimated glomerular filtration rate (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 60-90 mmHg, 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.

排除标准

•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 Diagnostic and Statistical Manual of Mental Disorders 5 (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. NOTE: Subjects receiving stable treatment of methadone and benzodiazepines will be allowed to be enrolled in the study even if the urine drug screen test is positive.
•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.
•Additional Exclusion Criteria for subjects with Renal Impairment (Group 2 to 5)
•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.
•Additional Exclusion Criteria for Subjects with ESRD (Group 5)
•Blood hemoglobin <10 g/dL at Screening.

研究组 & 干预措施

Group 1: Normal Renal Function

Experimental

Participants with normal renal function receive a 3 mg single dose of cytisinicline.

干预措施: cytisinicline (Drug)

Group 2: Mild Renal Impairment

Experimental

Participants with mild renal impairment receive a 3 mg single dose of cytisinicline.

干预措施: cytisinicline (Drug)

Group 3: Moderate Renal Impairment

Experimental

Participants with moderate renal impairment receive a 3 mg single dose of cytisinicline.

干预措施: cytisinicline (Drug)

Group 4: Severe Renal Impairment

Experimental

Participants with severe renal impairment receive a 3 mg single dose of cytisinicline.

干预措施: cytisinicline (Drug)

Group 5: ESRD Participants Undergoing Dialysis

Experimental

Participants with ESRD undergoing dialysis receive a 3 mg single dose of cytisinicline on 2 occasions: after and prior to a dialysis session.

干预措施: cytisinicline (Drug)