A Phase 1, Open-Label, Parallel Group Trial to Evaluate the Effect of Renal Impairment and Dialysis Treatment on the Pharmacokinetics of a Single Intravenous Dose of TAK-954
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 4
- 主要终点
- Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2
研究概览
简要总结
The purpose of this study is to evaluate the effect of varying degrees of renal function on the PK of TAK-954 following single-dose IV administration and to investigate the impact of hemodialysis on the PK of single IV doses of TAK-954.
详细描述
The drug being tested in this study is called TAK-954. This study will evaluate the effect of varying degrees of renal function on the PK of TAK-954 following single-dose IV administration and to investigate the impact of hemodialysis on the PK of single IV doses of TAK-954.
The study will enroll approximately up to 40 participants. Participants will be enrolled in one of the 5 treatment groups based on their renal impairment which will be determined based on Cockcroft and Gault (CG) equation as follows:
- Group A TAK-954 0.2 mg: Healthy Participants
- Group B TAK-954 0.2 mg: Mild Renal Impairment
- Group C TAK-954 0.2 mg: Moderate Renal Impairment
- Group D TAK-954 0.2 mg: Severe Renal Impairment or End-stage Renal Disease (ESRD) Without Hemodialysis
- Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD) With Hemodialysis
All participants in groups A to D will receive a single dose of TAK-954 and two single doses in Group E.
Enrollment in Group B (Mild) and Group E (ESRD requiring dialysis) will be based on assessment of safety and available PK data from Group C and Group D respectively.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •All participants: Male and female participants (non-childbearing potential) who are aged 18 to 75 years, inclusive, with a body mass index (BMI) between 18 to 35 kilogram per square meter (kg/m^2).
- •Group A: As much as possible, the healthy participants with normal renal function (creatinine clearance [CLcr] greater than or equal to [>=] 90 milliliter per minute [mL/min]) should be comparable to participants with renal impairment with respect to median age and weight (approximately 50 percent [%] of healthy participants on each side of the median age and weight of currently enrolled renally-impaired participants grouped together), sex, and race. This will be decided by the investigators in discussion with Takeda.
- •Groups B to E: Participants who have stable RI, defined as no clinically significant change in disease status, as documented by the participant's most recent CLcr assessment; serum creatinine must not vary more than approximately 30% from Screening to Day -1 to confirm stable disease. Participants should also be in good health commensurate with their renal status.
- •Group B: Participants with mild RI (CLcr 60 to less than [<] 90 mL/min).
- •Group C: Participants with moderate RI (CLcr 30 to <60 mL/min).
- •Group D: Participants with severe RI or ESRD but not requiring dialysis (CLcr <30 mL/min).
- •Group E: Participants with ESRD requiring dialysis (<15 mL/min requiring hemodialysis at least 3 times/week, and having been on the same dialysis treatment regimen for at least 1 month before trial entry).
- •Participants should be on a stable drug regimen defined as not starting a new drug or changing dosage within 7 days or 5 half-lives (whichever is longer) before dosing with TAK-954.
排除标准
- •All participants:
- •Are renal allograft recipients within 1 year of screening.
- •Have a history of gastrointestinal (GI) motility disorder or intestinal obstruction.
- •Have urinary incontinence without catheterization.
- •Group A: Participants who, in the discretion of the investigator, have a history of clinically significant endocrine, GI, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases will be excluded from the trial.
- •Groups B to E:
- •Receive dialysis other than intermittent dialysis (except Group E).
- •Have renal disease secondary to hepatic disease (hepatorenal syndrome).
- •At the discretion of the investigators, have any significant hepatic, cardiac, or pulmonary disease or participants who are clinically nephrotic.
研究组 & 干预措施
Group A TAK-954 0.2 mg: Healthy Participants
Participants with normal renal function receive TAK-954 0.2 milligram (mg), infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
干预措施: TAK-954 (Drug)
Group B TAK-954 0.2 mg: Mild Renal Impairment
Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
干预措施: TAK-954 (Drug)
Group C TAK-954 0.2 mg: Moderate Renal Impairment
Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
干预措施: TAK-954 (Drug)
Group D TAK-954 0.2 mg: Severe Renal Impairment
Participants without hemodialysis or End-stage Renal Disease (ESRD) receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
干预措施: TAK-954 (Drug)
Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD)
Participants with hemodialysis receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 4-day period followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 4-day period.
干预措施: TAK-954 (Drug)
结局指标
主要结局
Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2
时间窗: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 1
时间窗: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; CLR: Renal Clearance for TAK-954 in Period 1
时间窗: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Groups A, C and D; 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 120 hours) post-infusion
Groups A, C and D; AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for TAK-954 (Free and Total)
时间窗: Day 1 pre-infusion and at multiple time points (up to 72 hours) post-infusion
Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine
时间窗: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 2
时间窗: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Groups A, C and D; CLR: Renal Clearance for TAK-954
时间窗: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; CLR: Renal Clearance for TAK-954 in Period 2
时间窗: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; CLD: Clearance of Dialysate for TAK-954 in Period 2
时间窗: Day 1 pre-infusion and at multiple time points (up to 4 hours) post-infusion
Groups A, C and D; AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Free and Total)
时间窗: Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total)
时间窗: Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine
时间窗: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 1
时间窗: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
次要结局
未报告次要终点