A Phase 1 Study to Assess Absolute Bioavailability of TAK-831 and to Characterize Mass Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]TAK-831 in Male Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Urine (Cum%Dose [UR])
研究概览
简要总结
The purpose of this study is to determine ABA of TAK-831 following a single microdose intravenous administration of 50 microgram (μg) (approximately 1 microcurie [μCi]) [14C]TAK-831 and a single oral administration of 500 milligram (mg) TAK-831 tablets in Period 1, and to assess the mass balance, characterize the PK of TAK-831 in plasma and urine, and total radioactivity concentration equivalents in plasma and whole blood following a single oral suspension dose of 500 mg (approximately 100 μCi) [14C]TAK-831 in Period 2.
详细描述
The drug being tested in this study is called TAK-831 (also known as luvadaxistat). The study will determine ABA in Period 1, and the absorption, metabolism, excretion, and mass balance of TAK-831 after single oral administration in Period 2 in healthy adult male participants, by collecting plasma, urine, and feces samples for drug concentration analysis, and plasma, whole blood, urine, and fecal samples for total radioactivity analysis and metabolic profiling.
The study will enroll approximately 6 participants. The study is designed to consist of 2 periods: Period 1 (ABA study period) and Period 2 (absorption, distribution, metabolism, and elimination [ADME] study period). In Period 1 (ABA study period), all participants will receive a single unlabelled oral dose of TAK-831 as tablet and a microdose intravenous infusion of 50 μg (approximately 1 μCi) [14C]TAK-831, followed by a washout period of 8 days before the dose in Period 2. In Period 2 (ADME study period), all participants will receive a single dose of 500 mg (approximately 100 μCi) [14C]TAK-831 as an oral suspension.
This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 65 days including screening period. Participants will be contacted approximately 30 days after the last dose of study drug for a follow-up assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Weighs at least 45 kilogram (kg) and body mass index (BMI) greater than or equal to (>=) 18.0 and less than (˂) 32.0 kilogram per square meter (kg/m^2) at screening.
排除标准
- •Seated blood pressure is less than 90/40 millimeter of mercury (mmHg) or greater than 140/90 mmHg at screening.
- •Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening.
- •Estimated creatinine clearance <80 milliliter per minute (mL/min) at screening.
- •Has tattoo(s) or scarring at or near the site of intravenous infusion or any other condition which may interfere with infusion site examination, in the opinion of the Investigator.
- •Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing.
- •Has received radiolabeled substances or has been exposed to radiation sources within 12 months of first dosing or is likely to receive radiation exposure or radioisotopes within 12 months of first dosing such that participation in this study would increase their total exposure beyond the recommended levels considered safe (that is weighted annual limit recommended by the International Commission on Radiological Protection [ICRP] of 3000 milli roentgen equivalent man [mrem]).
- •Has been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to the first dosing and throughout the study.
- •Donation of blood or significant blood loss within 56 days prior to the first dosing.
- •Plasma donation within 7 days prior to the first dosing.
研究组 & 干预措施
TAK-831 500 mg + [14C]TAK-831 50 μg + [14C]TAK-831 500 mg
TAK-831 500 mg, tablet, orally, once on Day 1, followed by [14C]TAK-831 50 micrograms (μg) [approximately 1 microcurie (μCi)], infusion, intravenously (IV), once on Day 1 of Treatment Period 1, followed by a washout period of 8 days, further followed by [14C]TAK-831 500 mg (approximately 100 μCi), suspension, orally, once under fasted state on Day 1 of Treatment Period 2.
干预措施: TAK-831 Oral Tablet (Drug)
TAK-831 500 mg + [14C]TAK-831 50 μg + [14C]TAK-831 500 mg
TAK-831 500 mg, tablet, orally, once on Day 1, followed by [14C]TAK-831 50 micrograms (μg) [approximately 1 microcurie (μCi)], infusion, intravenously (IV), once on Day 1 of Treatment Period 1, followed by a washout period of 8 days, further followed by [14C]TAK-831 500 mg (approximately 100 μCi), suspension, orally, once under fasted state on Day 1 of Treatment Period 2.
干预措施: [14C]TAK-831 IV Infusion (Drug)
TAK-831 500 mg + [14C]TAK-831 50 μg + [14C]TAK-831 500 mg
TAK-831 500 mg, tablet, orally, once on Day 1, followed by [14C]TAK-831 50 micrograms (μg) [approximately 1 microcurie (μCi)], infusion, intravenously (IV), once on Day 1 of Treatment Period 1, followed by a washout period of 8 days, further followed by [14C]TAK-831 500 mg (approximately 100 μCi), suspension, orally, once under fasted state on Day 1 of Treatment Period 2.
干预措施: [14C]TAK-831 Oral Suspension (Drug)
结局指标
主要结局
Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Urine (Cum%Dose [UR])
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Feces (Cum%Dose [Fe])
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-831
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Whole Blood Radioactivity Concentration
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Total Radioactivity Expressed as Cumulative Amount of [14C]TAK-831 Eliminated in Urine and Feces Combined (Combined CumAe)
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: t(1/2)z: Terminal Disposition Phase Half-life of TAK-831 in Plasma
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-831
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-831
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Cmax: Maximum Observed Plasma Radioactivity Concentration
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Radioactivity Concentration
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Cmax: Maximum Observed Whole Blood Radioactivity Concentration
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Tmax: Time to Reach the Maximum Whole Blood Radioactivity Concentration (Cmax)
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: AUClast: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: CLR: Renal Clearance for TAK-831 in Urine
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 1: Percent Absolute Bioavailability (%F) for TAK-831
时间窗: Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1
Bioavailability is defined as the proportion of a drug which enters the circulation when introduced into the body and so is able to have an active effect. Percent absolute bioavailability, calculated for plasma TAK-831 as \[Actual Dose (IV) x AUCinf (oral)\] / \[Actual Dose (oral) x AUCinf (IV)\] x 100.
Period 2: Total Radioactivity Expressed as Cumulative Percentage of Dose of [14C]TAK-831 Eliminated in Urine and Feces Combined [Combined Cum%Dose]
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Cmax: Maximum Observed Plasma Concentration of TAK-831
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2: Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax)
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: AUCinf: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: AUClast: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: AUCinf: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity
时间窗: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
次要结局
- Period 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 After Oral Administration(Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1)
- Period 1: t(1/2)z: Terminal Disposition Half-life for TAK-831 After Oral and [14C]TAK-831 After IV Administration in Plasma(Day 1 pre-dose and at multiple time points (up to 96.5 hours for TAK-831 and up to 95 hours for [14C]TAK-831) post-dose)
- Number of Participants With TEAEs Related to Electrocardiogram (ECG)(Up to Day 14)
- Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for TAK-831 After Oral Administration(Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1)
- Period 1: Ceoi: Plasma Concentration at the End of Infusion for [14C]TAK-831(Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1)
- Period 1: Cmax: Maximum Observed Plasma Concentration for TAK-831 After Oral Administration(Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1)
- Period 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 After Oral Administration(Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1)
- Period 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]TAK-831 After IV Administration(Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1)
- Period 1: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]TAK-831 After IV Administration(Day 1 pre-dose and at multiple time points (up to 95 hours) post-dose in Treatment Period 1)
- Number of Participants With TEAEs Related to Vital Signs(Up to Day 14)
- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)(From first dose of study drug up to 30 days after last dose of study drug (up to approximately 38 days))
- Number of Participants With TEAEs Related to Laboratory Parameters(Up to Day 14)