A Phase 1, Open-label, 2-part, Single-dose Study of the Absorption, Metabolism, and Excretion of Oral [14C]-Xevinapant, and Absolute Oral Bioavailability of Xevinapant in 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 Recovery Measured Through Total Radioactivity Excreted in Expired Air, Urine and Feces
研究概览
简要总结
The purpose of the study is to determine absorption, metabolism, and excretion of a single oral dose of [14C]-xevinapant. This information will enable assessment of absorption and clearance mechanisms of [14C]-xevinapant as well as identify metabolites. In addition, the study will allow to determine absolute bioavailability of xevinapant and understand its intravenous pharmacokinetics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Part 1: Males of any race, between 35 and 65 years of age, inclusive. Part 2: Males of any race, between 18 and 65 years of age, inclusive
- •Body mass index between 18.0 and 30.0 kilograms per meter square (kg/m^2), inclusive
- •Weight between 50 kilograms (kg) and 110 kg, inclusive
- •History of a minimum of 1 bowel movement per day.
- •Willing to adhere to the prohibitions and restrictions specified in the study protocol
排除标准
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee)
- •History of alcohol consumption of >21 units per week. One unit of alcohol equals 12 ounce (oz) [360 millilitre (mL)] beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine.
- •Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing, or less than 5 times the half-life, whichever is longer, prior to administration of study drug
- •Poor peripheral venous access
- •Have participated in any clinical study involving a radiolabeled investigational product within 12 months prior to check-in.
研究组 & 干预措施
Radiolabeled Xevinapant Oral Solution
Participants will receive:
• single oral dose of [14C]-xevinapant, as an oral solution
干预措施: Radiolabelled Xevinapant 200 mg (Oral Solution) (Drug)
Radiolabeled Xevinapant Intravenous Solution + Xevinapant Oral Solution
Participants will receive:
• single oral dose of xevinapant, as an oral solution followed by an IV bolus of [14C]-xevinapant, solution for infusion
干预措施: Radiolabelled Xevinapant 100 μg (IV Solution) (Drug)
Radiolabeled Xevinapant Intravenous Solution + Xevinapant Oral Solution
Participants will receive:
• single oral dose of xevinapant, as an oral solution followed by an IV bolus of [14C]-xevinapant, solution for infusion
干预措施: Xevinapant 200 mg (Oral Solution) (Drug)
结局指标
主要结局
Mass Balance Recovery Measured Through Total Radioactivity Excreted in Expired Air, Urine and Feces
时间窗: Up to Day 29
Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity); Time 0 to 24 Hours (AUC0-24); Time 0 to Last Quantifiable Concentration (AUC0-last) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma
时间窗: Up to Day 29
Apparent Terminal Elimination Half-life (T1/2) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma
时间窗: Up to Day 29
Maximum Observed Concentration (Cmax) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma
时间窗: Up to Day 29
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma
时间窗: Up to Day 29
Absolute Bioavailability (F) of Xevinapant in Plasma
时间窗: Up to Day 5
Absolute Bioavailability (F) = (AUC0-infinity \[oral\]/ dose \[oral\]) /(AUC0-infinity \[IV\]/ dose \[IV\])
Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma
时间窗: Up to Day 29
Apparent Total Clearance (CL/F) of Total Radioactivity in Blood and Plasma and of Xevinapant and Metabolite in Plasma
时间窗: Up to Day 29
Renal Clearance (CLr) of Total Radioactivity, Xevinapant and Metabolite
时间窗: Up to Day 29
Xevinapant Metabolite Concentrations in Urine, Feces, Blood and Plasma
时间窗: Up to Day 8
次要结局
- Safety and Tolerability as Measured by Number of Participants With Clinically significant Laboratory Abnormalities(Up to Day 29)
- Safety and Tolerability as Measured by Number of Participants With Clinically significant 12-lead ECG Parameters Abnormalities(Up to Day 29)
- Safety and Tolerability as Measured by Number of Participants With Clinically significant Vital Signs Abnormalities(Up to Day 29)
- Plasma Protein Binding Expressed as Fraction unbound, fu of Xevinapant(Up to Day 8)
- Safety and Tolerability as Measured by Number of Participants With Treatment-Emergent Adverse Events(Up to Day 29)
- Safety and Tolerability as Measured by Number of Participants With Clinically significant Physical Examination Abnormalities(Up to Day 29)
- Blood to Plasma Ratio of Xevinapant and Metabolite(Up to Day 8)