A Phase 1, Non-Randomized, Open-Label Trial to Evaluate the Effect of Hepatic Impairment on the Single Dose Pharmacokinetics of Intravenous TAK-954
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- AUClast: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Total and Free)
研究概览
简要总结
The purpose of this study is to evaluate the effect of varying degrees of hepatic function on the single dose PK of IV TAK-954.
详细描述
The drug being tested in this study is called TAK-954. This study will evaluate the safety and tolerability of single intravenous doses of TAK-954 in participants with varying degrees of hepatic function.
The study will enroll approximately up to 32 participants. Participants will be enrolled in one of the 4 treatment groups based on their degree of hepatic impairment which will be determined based on Child-Pugh Score as follow:
- Group 1 TAK-954 0.2 mg: Mild Hepatic Impairment (Child Pugh Class A)
- Group 2 TAK-954 0.2 mg: Moderate Hepatic Impairment (Child Pugh Class B)
- Group 3 TAK-954 0.2 mg: Severe Hepatic Impairment (Child Pugh Class C)
- Group 4 TAK-954 0.2 mg: Healthy Participants
The Child-Pugh classification will assess the severity of 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy grade) on a scale of 1 (none) to 3 (moderate). Total hepatic impairment score ranges from 5 (mild) to 15 (severe) where higher score indicates more severity.
All participants will receive a single dose of TAK-954 0.2 mg on Day 1.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female participants (non-childbearing potential), with a body mass index (BMI) between 18 to 35 kilogram per square meter (kg/m^2) (All participants).
- •Participants with hepatic impairment who are medically stable as determined by the investigator, based on medical history and clinical evaluations including physical examinations, clinical laboratory tests, vital sign measurements, and 12-lead ECGs performed at the Screening Visit and at check-in on Day -1 (Group 1 to 3).
- •Healthy participants (Group 4).
排除标准
- •Participants who have:
- •A history of hepatic carcinoma, hepatorenal syndrome, or presence of a liver mass by ultrasound, CT or MRI, or acute liver disease caused by an infection or drug toxicity (Group 1 to 3).
- •Have severe hepatic encephalopathy ([greater than] > Grade II Portal Systemic Encephalopathy Score) (Group 1 to 3).
- •Surgical porto-systemic shunts, including transjugular intrahepatic portosystemic shunt (Group 1 to 3).
- •A history of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 1 month prior to trial entry (Group 1 to 3).
- •Bilirubin levels above 5 times the upper limit of normal (ULN) at screening or Day -1 for Groups 1 and 2, there is no limit for Group
- •Severe/advanced ascites and/or pleural effusion which requires emptying and albumin supplementation, as judged by the investigator (Group 1 to 3).
- •Renal creatinine clearance (CLcr) less than or equal to (<=) 50 milliliter per minute (mL/min), calculated using the Cockcroft-Gault equation from the serum creatinine measurement taken at screening (Group 1 to 3).
- •Who have a history of clinically significant endocrine, gastrointestinal (GI) (including motility disorder and intestinal obstruction), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases will be excluded from the trial (Group 4).
研究组 & 干预措施
Group 1 Mild Hepatic Impairment: TAK-954 0.2 mg
TAK-954 0.2 milligram (mg), intravenous, administered as 60-minute infusion, once on Day 1.
干预措施: TAK-954 (Drug)
Group 2 Moderate Hepatic Impairment: TAK-954 0.2 mg
TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.
干预措施: TAK-954 (Drug)
Group 3 Severe Hepatic Impairment: TAK-954 0.2 mg
TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.
干预措施: TAK-954 (Drug)
Group 4 Healthy Participants: TAK-954 0.2 mg
TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.
干预措施: TAK-954 (Drug)
结局指标
主要结局
AUClast: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Total and Free)
时间窗: Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)
时间窗: Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-954 (Total and Free)
时间窗: Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
次要结局
- Number of Participants With Markedly Abnormal Values of Vital Signs(Up to 14 days after the last dose of study drug (Day 15))
- Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values(Up to 14 days after the last dose of study drug (Day 15))
- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)(Baseline up to 30 days after last dose of study drug (Day 31))
- Number of Participants With Clinically Significant Physical Examination Findings(Up to 14 days after the last dose of study drug (Day 15))
- Number of Participants With Markedly Abnormal Electrocardiograms (ECGs)(Up to 14 days after the last dose of study drug (Day 15))