A Single-dose, Open-label, Single Arm Study to Investigate PK of Xevinapant (Debio 1143) and Its Metabolite, D-1143-MET1 in Healthy East Asian Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sample Time (AUC0-tlast) of Xevinapant (Debio 1143)
研究概览
简要总结
The purpose of this study was to evaluate the pharmacokinetics (PK) of Xevinapant (Debio 1143) and its metabolite D-1143-MET1 as well as safety and tolerability of Xevinapant (Debio 1143) in healthy East Asian participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participant of Japanese or other East Asian origin. Group 1: Japanese participants must be first generation (born in Japan) with both biological parents and all 4 biological grandparents being Japanese native born, lived for less than (<)10 years outside of Japan, and have no significant change in lifestyle since leaving Japan. Group 2: Other non-Japanese East Asian participants must have both biological parents and 4 biological grandparents of East Asian descent, lived for <10 years outside of their countries, and have no significant change in lifestyle since leaving from there. East Asia includes Korea or Greater China
- •Overtly healthy participants as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring (blood pressure, heart rate, and 12-lead resting ECG)
- •Have a body weight within 50 and 110 kilograms [kg] (inclusive) and Body Mass Index (BMI) within the range 18.0 to 32.0 kilograms per meter square [Kg/m^2] (inclusive)
- •Other protocol defined inclusion criteria could apply
排除标准
- •History of clinically relevant disease of any organ system that may interfere with the objectives of the study or provide a risk to the health of the participant
- •History of relevant drug hypersensitivity, ascertained or presumptive allergy/ hypersensitivity to the active drug substance and/or formulation ingredients history of serious allergic reactions leading to hospitalization or any other allergy reaction in general, which the Investigator considers may affect the safety of the participant and/or outcome of the study
- •Ongoing or active clinically significant viral (including Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), bacterial or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives less than or equal to (<=) 4 weeks prior to or during Screening Period, or completion of oral anti-infectives <= 2 weeks prior to Screening Visit. Vaginal candidiasis, onychomycosis, and genital or oral herpes simplex virus considered to be sufficiently controlled will not be exclusionary
- •History of splenectomy
- •History of any malignancy (hematologic or solid tumor) before the Screening Visit, except for adequately treated superficial basal cell carcinoma of the skin (no more than 3 lesions requiring treatment in lifetime) or carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix
- •History of or a positive screening test for hepatitis B, hepatitis C, or human immunodeficiency virus type I and II
- •Use of any investigational drug in any clinical study within 5 half-lives from last administration
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Group 1: Japanese Participants: Xevinapant (Debio 1143)
Xevinapant (Debio 1143) was administered in Healthy Japnaese participants at a dose of 200 milligrams (mg), orally under fasted conditions.
干预措施: Xevinapant (Debio 1143) (Drug)
Group 2: Non-Japanese East Asian Participants: Xevinapant (Debio 1143)
Xevinapant (Debio 1143) was administered in Healthy Non- Japanese participants at a dose of 200 mg, orally under fasted conditions.
干预措施: Xevinapant (Debio 1143) (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sample Time (AUC0-tlast) of Xevinapant (Debio 1143)
时间窗: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose
The area under the concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Maximum Observed Plasma Concentration (Cmax) of Xevinapant (Debio 1143)
时间窗: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose
Cmax was obtained directly from concentration versus time curve.
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Xevinapant (Debio 1143)
时间窗: Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose
The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at t last , as estimated using the linear regression from Terminal first order (elimination) rate constant (Lambda z) determination. AUC0-inf = AUC0-t plus Clast pred/lambda z. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
次要结局
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity(Baseline (Day 1) up to Day 8)
- Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values(Baseline (Day 1) up to Day 8)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite D-1143-MET1(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)
- Apparent Terminal Half-Life (t1/2) of Metabolite D-1143-MET1(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)
- Metabolite-to-parent Molar Ratio for AUC0-t (MR_AUC0-t) of Xevinapant and D-1143-MET1(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)
- Metabolite-to-parent Molar Ratio for AUC0-inf (MR_AUC0-inf) of Xevinapant and D-1143-MET1(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)
- Metabolite-to-parent Molar Ratio for Cmax (MR_Cmax) of Xevinapant and D-1143-MET1(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Related TEAE's(Up to Day 8)
- Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings(Baseline (Day 1) up to Day 8)
- Number of Participants With Clinically Significant Change From Baseline in Vital Signs(Baseline (Day 1) up to Day 8)
- Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of Xevinapant (Debio 1143)(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Xevinapant (Debio 1143)(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)
- Apparent Terminal Half-Life (t1/2) of Xevinapant (Debio 1143)(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)
- Apparent Clearance (CL/f) of Xevinapant (Debio 1143)(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)
- Apparent Volume of Distribution During Terminal Phase (Vz/f) of Xevinapant (Debio 1143)(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)
- Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t Last) of Metabolite D-1143-MET1(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)
- Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of Metabolite D-1143-MET1(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
- Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metabolite D-1143-MET1(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)
- Maximum Observed Plasma Concentration (Cmax) of Metabolite D-1143-MET1(Predose, 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 , 36, 48 and 72 hours postdose)