An Open-Label, Single-Dose, Single-Period Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-Olorofim Administered Via the Oral Route to Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Mass balance
研究概览
简要总结
Single-centre, open-label, non-randomised, single dose study in 2 cohorts of healthy subjects. It is planned to enrol 6 healthy male subjects in Cohort A (standard mass balance and metabolite profiling cohort) and up to 6 subjects in Cohort B (biliary evaluation cohort); each subject will receive a single oral administration of 120 mg [14C]-olorofim oral solution containing approximately 3.7 MBq (100 µCi).
详细描述
Subjects will be screened up to 28 days prior to dosing and eligible subjects will be admitted to the Clinical Research Unit (CRU) on the day prior to dosing (Day-1). Each subject will be dosed on the morning of Day 1 after an overnight fast.
Cohort A:
Subjects will remain resident in the CRU up to 336 h post-dose (Day 15), with whole blood, plasma, urine and faeces collected throughout this period. There may be up to two further 24 h residency periods (Days 21 to 22 and Days 28 to 29) for collection of plasma, urine and faeces if discharge criteria are not met.
Cohorts B1 and B2:
Subjects will remain resident in the CRU up to 96 h post-dose (Day 5) for collection of plasma, urine, faeces and bile. Subjects will return for a short follow-up visit on Day 10. Cohort B1 subjects will have bile sampling up to 6 h postdose and Cohort B2 subjects will have bile sampling up to 12 h postdose. Cohort B divided into 2 sub-cohorts for logistical reasons only.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •healthy males age 18 to 55 years of age with body mass index of 18 to 30 kg/m2 (inclusive), and a body weight of 50 to 100 kg (inclusive).
- •Subjects must be in good health as determined by a medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory evaluations (congenital non haemolytic hyperbilirubinaemia is NOT acceptable).
- •Must have regular bowel movements (ie, average stool production of ≥1 and ≤3 stools per day).
排除标准
- •Subjects with or history of clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatry, respiratory, metabolic, endocrine, ocular haematological or other major disorders as determined by the investigator
- •Subjects who have received any prescribed systemic or topical medication within 14 days of the dose administration
- •Subjects who have used any non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the dose administration
- •Subjects who have received any medications, including St John's Wort, known to chronically alter drug absorption or elimination processes within 30 days of the dose administration
- •Current smokers and those who have smoked or used nicotine containing products (eg electronic cigarettes) within the 3 months prior to check-in.
- •Radiation exposure, including that from the present study exceeding 1 mSv in the last 12 months or 5 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study.
研究组 & 干预措施
Cohort A (mass balance)
evaluation of mass balance and metabolite profiling
干预措施: Olorofim (Drug)
Cohort B (biliary evaluation)
evaluation of biliary elimination
干预措施: Olorofim (Drug)
结局指标
主要结局
Mass balance
时间窗: 28 days
% dose recovered in urine and faeces
Metabolite profiling
时间窗: 15 days
number of metabolites in plasma, urine and faeces \> 10% of circulating radioactivity
次要结局
- Maximum plasma concentration (Cmax) for olorofim, F902412 and total radioactivity(15 days)
- time of maximum plasma concentration (Tmax) for olorofim, F902412 and total radioactivity(15 days)
- Number of subjects with treatment-related adverse events(28 days)
- biliary elimination(5 days)
- elimination half life (t1/2) for olorofim, F902412 and total radioactivity(15 days)
- Area under plasma concentration curve (AUC) for olorofim, F902412 and total radioactivity(15 days)
- Number of subjects with clinically significant change from baseline in vital signs, laboratory parameters, and electrocardiogram findings(28 days)