Single-center, Open-label Study With 14C-labeled ACT-128800 to Investigate the Mass Balance, Pharmacokinetics, and Metabolism Following Single Oral Administration to Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Cumulative recovery of total radioactivity expressed as a percentage of the administered dose (mass balance) in the faeces
研究概览
简要总结
The study was conducted to investigate the metabolism and mass balance of ACT-128800, and to identify the elimination pathways (metabolism and excretion) of ACT-128800 and compare them with the known metabolic profiles of ACT-128800 in animals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent prior to any study-mandated procedure.
- •Male and aged between 45 and 65 years (inclusive) at screening.
- •No clinically significant findings on physical examination performed at screening.
- •Body mass index (BMI) between 18-28 kg/m^2 (inclusive) at screening.
- •Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and heart rate 55-90 bpm (inclusive), measured on the leading arm, after 5 minutes in the supine position at screening. These criteria should also be met before the administration of the first dose.
- •12-lead electrocardiogram without clinically relevant abnormalities at screening.
- •Clinical chemistry, hematology, and urinalysis results not deviating from the normal range to a clinically relevant extent at screening.
- •Negative results from urine drug screen at screening.
- •Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.
排除标准
- •Known hypersensitivity to any excipients of the drug formulation.
- •Treatment with another investigational drug within the 3 months prior to screening.
- •History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
- •Excessive caffeine consumption, defined as ≥ 800 mg per day at screening.
- •History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drug.
- •Smoking within the 3 months prior to screening.
- •Any immunosuppressive treatment within 6 weeks before study drug administration.
- •Previous treatment with any prescribed or over-the-counter medications (including herbal medicines such as St John's Wort) within 2 weeks prior to screening.
- •Loss of 250 mL or more of blood within the 3 months prior to screening.
- •Lymphopenia (< 1,100 lymphocytes/μL).
- •Viral, fungal, bacterial or protozoal infection within 4 weeks before study drug administration.
- •Positive hepatitis B or hepatitis C serology, except for vaccinated subjects, at screening.
- •Positive human immunodeficiency virus serology 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.
- •Exposure to artificial ionizing radiation (e.g., X-ray, thyroid scan, study with radiolabeled compound) in the 12-month period before screening.
- •A history of clinically relevant constipation (defined as lasting more than 3 days) in the 4-week period before screening.
研究组 & 干预措施
ACT-128800
Subjects received a single oral dose of 40 mg 14C-labeled ACT-128800 (one capsule)
干预措施: ACT-128800 (Drug)
结局指标
主要结局
Cumulative recovery of total radioactivity expressed as a percentage of the administered dose (mass balance) in the faeces
时间窗: Up to end of study, approximately 240 hours
Between Day -3 and Day -1, a baseline faeces sample was collected in a light-protected polypropylene box from each subject. From Day 1 (post-dose) to Day 10 (inclusive), all faeces samples and the toilet paper were collected in pre-weighed, light-protected polypropylene boxes. Each faeces sample was collected in a separate box and weighed. The weight of the sample and the time of collection were recorded. All faecal samples were frozen as soon as possible and stored in an upright position at -70 °C or below.The total amount of radioactivity was measured using a liquid scintillation counter.
Cumulative recovery of total radioactivity expressed as a percentage of the administered dose (mass balance) in the urine
时间窗: Up to end of study, approximately 240 hours
On Day 1, immediately prior to the intake of study drug, subjects were instructed to empty their bladders. Thereafter, following drug intake all urine produced was collected for 10 days up to Day 11 (morning). Following administration of 14C-ACT-128800, urine samples were collected in three consecutive 8-hour intervals, from 0-8 h, 8-16 h, and 16-24 h. From Day 2 to Day 10 (inclusive), urine samples were collected at 24-hour intervals. In case of an extended observation period, urine samples were also collected at 24-hour intervals. The total amount of radioactivity was measured using a liquid scintillation counter.
次要结局
- Maximum concentration (Cmax) of 14C-radioactivity in whole blood(Up to end of study, approximately 240 hours)
- Area under the plasma concentration-time curve (AUC(0-infinity)) of 14C-radioactivity in whole blood(Up to end of study, approximately 240 hours)
- Half life (t1/2) of 14C-radioactivity in whole blood(Up to end of study, approximately 240 hours)
- Area under the plasma concentration-time curve (AUC(0-t)) of 14C-radioactivity in whole blood(Up to end of study, approximately 240 hours)
- Time to maximum concentration (tmax) of 14C-radioactivity in whole blood(Up to end of study, approximately 240 hours)
- Maximum concentration (Cmax) of 14C-radioactivity in plasma(Up to end of study, approximately 240 hours)
- Time to maximum concentration (tmax) of 14C-radioactivity in plasma(Up to end of study, approximately 240 hours)
- Area under the plasma concentration-time curve (AUC(0-t)) of 14C-radioactivity in plasma(Up to end of study, approximately 240 hours)
- Area under the plasma concentration-time curve (AUC(0-infinity)) of 14C-radioactivity in plasma(Up to end of study, approximately 240 hours)
- Half life (t1/2) of 14C-radioactivity in plasma(Up to end of study, approximately 240 hours)
- Maximum concentration (Cmax) of ACT-12880 in plasma(Up to end of study, approximately 240 hours)
- Time to maximum concentration (tmax) of ACT-12880 in plasma(Up to end of study, approximately 240 hours)
- Area under the plasma concentration-time curve (AUC(0-t)) of ACT-12880 in plasma(Up to end of study, approximately 240 hours)
- Area under the plasma concentration-time curve (AUC(0-infinity)) of ACT-12880 in plasma(Up to end of study, approximately 240 hours)
- Half life (t1/2) of ACT-12880 in plasma(Up to end of study, approximately 240 hours)
- Total lymphocyte count(Up to end of study, approximately 240 hours)
- Change in systolic blood pressure from baseline up to end of study(Up to end of study, approximately 240 hours)
- Change in diastolic blood pressure from baseline up to end of study(Up to end of study, approximately 240 hours)
- Change in heart rate from baseline up to end of study(Up to end of study, approximately 240 hours)
- Change in body temperature from baseline up to end of study(Up to end of study, approximately 240 hours)
- Change in body weight from baseline to end of study(Up to end of study, approximately 240 hours)