An Open-label, Parallel-group Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cenerimod After Single-dose Administration in Subjects With Hepatic Impairment and in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Area under the plasma concentration-time curves (AUC0-t): cenerimod
研究概览
简要总结
This is a prospective, open-label, single-dose, phase 1 study, to assess the effect of mild and moderate hepatic impairment on the pharmacokinetics of cenerimod (ACT-334441).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent in a language understandable to the participant prior to any study-mandated procedure.
- •Women of child bearing potential must have a negative serum pregnancy test at screening, a negative urine pregnancy test on Day -1, and must agree to consistently and correctly use a highly effective method of contraception (i.e., failure rate of less than 1%).
- •Women of non-childbearing potential must have a medical history of previous bilateral salpingectomy, salpingo-oophorectomy or hysterectomy, premature ovarian failure confirmed by a specialist gynecologist; or, be post-menopausal, defined as 12 consecutive months with amenorrhea prior to screening without alternative medical cause and confirmed with a follicle-stimulating hormone test.
- •Body mass index of 18.0 to 32.0 kg/m2 (inclusive) at screening.
- •Negative SARS-CoV-2-testing prior to Day -1 or documented vaccination against COVID-19 at least 3 months prior screening.
- •Ability to communicate well with the investigator, in a language understandable to the participant, and to understand and comply with the requirements of the study.
排除标准
- •General (Group A, B and C)
- •Pregnant or lactating women.
- •Participation in a clinical study involving study treatment administration within 30 days prior to screening or in more than 2 clinical studies within 1 year prior to screening.
- •Previous exposure to cenerimod.
- •History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, elimination (ADME) of the study treatment except for those related to liver cirrhosis or appendectomy and herniotomy.
- •International Normalized Ratio greater than 2 at screening.
- •Encephalopathy grade greater than or equal to
- •Clinically relevant abnormalities on a 12-lead ECG, recorded after 5 minutes in the supine position at screening and on Day 1 pre-dose.
- •Presence of herpes simplex, disseminated zoster, or other opportunistic infections.
- •Vaccination with live or live attenuated vaccines in the previous 4 weeks.
- •Previous treatment with antiarrhythmic medications of class Ia or III 2 weeks or 5 half-lives, whichever is longer, prior to study treatment administration.
- •Active retinopathy or macular edema at screening.
- •Severe chronic obstructive pulmonary disease at screening.
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
- •Legal incapacity or limited legal capacity at screening.
- •Additional inclusion criteria for participants with hepatic impairment (Group A and B)
- •Clinically relevant findings in clinical laboratory tests (hematology, coagulation, clinical chemistry, and urinalysis) at screening and on Day -1, except for those related to liver cirrhosis.
- •Additional exclusion criteria for healthy subjects (Group C)
- •Clinically relevant findings in clinical laboratory tests (hematology, coagulation, clinical chemistry, and urinalysis) at screening and on Day -
- •Previous treatment with any prescribed medications (including vaccines) or over-the-counter (OTC) medications (including herbal medicines such as St. John's Wort, homeopathic preparations, vitamins, and minerals) within 2 weeks or 5 t½ prior to study treatment administration, whichever is longer (excluding contraceptives and HRT).
- •Aspartate aminotransferase and alanine aminotransferase above the upper limit of normal.
研究组 & 干预措施
Group A: Participants with mild hepatic impairment
Participants with mild hepatic impairment (Child-Pugh Score of 5 to 6).
干预措施: Cenerimod (Drug)
Group B: Participants with moderate hepatic impairment
Participants with moderate hepatic impairment (Child-Pugh Score of 7 to 9).
干预措施: Cenerimod (Drug)
Group C:Healthy participants
Healthy participants will be matched to the participants with hepatic impairment based on age and body weight.
干预措施: Cenerimod (Drug)
结局指标
主要结局
Area under the plasma concentration-time curves (AUC0-t): cenerimod
时间窗: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Maximum plasma concentration (Cmax): cenerimod.
时间窗: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Area under the plasma concentration-time curve from zero to infinity (AUC0-inf): cenerimod
时间窗: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Time to reach Cmax (tmax): cenerimod
时间窗: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Terminal half-life (t½): cenerimod
时间窗: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Plasma protein binding of cenerimod
时间窗: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Apparent clearance (CL/F) of cenerimod
时间窗: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
Apparent volume of distribution (Vz/F) of cenerimod
时间窗: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 98.
次要结局
- Adverse events and serious adverse events(Day 1 up to Day 105.)
- Total lymphocyte count(Multiple sampling at predefined times on Day 1 (pre-dose) up to Day 98.)
- Change from baseline at each time point of measurement in electrocardiogram QT interval(Pre-defined times on Day 1 (pre-dose) up to Day 105.)
- Change from baseline in body weight(Day -1 and Day 105.)
- Change from baseline in systolic and diastolic blood pressure (in the supine position)(Predefined times on Day 1 (pre-dose) up to Day 105.)
- Incidence of abnormal laboratory test results(Multiple sampling at predefined times on Day 1 (pre-dose) up to Day 105.)