An Open-Label, Single-Dose Study to Investigate the Pharmacokinetics of MK-8616 in Subjects With Moderate and Severe Renal Insufficiency
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Geometric Least Squares Mean Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) Following a Single IV Dose of Sugammadex
研究概览
简要总结
The purpose of this study is to evaluate the plasma pharmacokinetics of a single 4 mg/kg intravenous (IV) dose of sugammadex in participants with moderate and severe renal insufficiency compared to that in participants with normal renal function. The study consists of two parts. In Part 1, participants with renal insufficiency and healthy participants will be administered study drug by IV bolus injection into a peripheral vein. In Part 2, participants with renal insufficiency and healthy participants will be administered study drug as an IV bolus into a peripheral vein, through an IV catheter connected to IV tubing with injection port. Subjects who participate in Part 1 of study may be enrolled in Part 2, which would reduce the overall number of participants enrolled for the study.
详细描述
In each study period (i.e., Part 1 and Part 2), day of drug administration was defined to be Day 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All Participants:
- •Body Mass Index ≥18 to ≤40 kg/m^2
- •Females of childbearing potential must either be sexually inactive (abstinent) for 14 days prior to dosing and throughout the study or are using an acceptable birth control method
- •Females of non-childbearing potential must have undergone a sterilization procedure at least 6 months prior to dosing or are postmenopausal with amenorrhea for at least 1 year prior to dosing and have follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status
- •Male subjects must agree not to donate sperm from dosing until 90 days after dosing
- •Participants with Moderate or Severe Renal Insufficiency:
- •Health of participant is stable based on medical history, laboratory tests and other assessments
- •Clinical diagnosis of impaired stable renal function, and a creatinine clearance (CLcr) of <30 mL/min and not on hemodialysis for severe renal insufficiency participants, or 30 to <50 mL/min for moderate renal insufficiency participants
- •No clinically significant change in renal status for at least 1 month prior to dosing, and is not currently or has not previously been on hemodialysis
- •Healthy Control Participants:
- •Participant is medically healthy based on laboratory tests and other assessments
- •Age of the individual healthy participants in Part 1 of the study is aimed to be within the range of the mean age ± approximately 15 years of all participants with renal impairment in Part 1 of the study combined; this approach will also be applied with respect to age of participants in Part 2 of the study
- •CLcr ≥80 mL/min
排除标准
- •All Participants:
- •Mentally or legally incapacitated, significant emotional problems at screening or expected during the conduct of the study or history of a clinically significant psychiatric disorder over the last 5 years
- •History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurological disease whose current condition is considered unstable
- •History or presence of alcoholism and drug abuse within the past 6 months
- •History or presence of hypersensitivity or idiosyncratic reaction to the study medication or related compounds
- •Female participants who are pregnant or lactating
- •Positive results for the urine or saliva drug screen, or for the urine or breath alcohol screen
- •Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
- •Regular user of any medication (including over the counter) that would significantly alter renal function (e.g., cimetidine)
- •Donation of blood or significant blood loss within 56 days prior to dosing, or donation of plasma within 7 days prior to dosing
- •Participation in another clinical trial within 28 days prior to dosing
- •No participant may be enrolled more than once within Part
- •Subjects who participate in Part 1 of study may be enrolled in Part 2, but participants within Part 2 are not to be enrolled more than once in Part 2
- •Healthy Control Participants:
- •Participant has had a renal transplant or has had nephrectomy
研究组 & 干预措施
Severe Renal Insufficiency Participants: Part 1
Participants with severe renal insufficiency will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered by direct injection into a peripheral vein.
干预措施: sugammadex (Drug)
Moderate Renal Insufficiency Participants: Part 1
Participants with moderate renal insufficiency will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered by direct injection into a peripheral vein.
干预措施: sugammadex (Drug)
Healthy Control Participants: Part 1
Healthy control participants will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered by direct injection into a peripheral vein.
干预措施: sugammadex (Drug)
Severe Renal Insufficiency Participants: Part 2
Participants with severe renal insufficiency will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered into a peripheral vein through an IV catheter connected to an IV tubing with injection port. The IV tubing is connected to a saline bag. Free-flowing access to the vein will be confirmed immediately prior to dose administration, and dose will be followed by saline flush.
干预措施: sugammadex (Drug)
Moderate Renal Insufficiency Participants: Part 2
Participants with moderate renal insufficiency will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered into a peripheral vein through an IV catheter connected to an IV tubing with injection port. The IV tubing is connected to a saline bag. Free-flowing access to the vein will be confirmed immediately prior to dose administration, and dose will be followed by saline flush.
干预措施: sugammadex (Drug)
Healthy Control Participants: Part 2
Healthy control participants will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered into a peripheral vein through an IV catheter connected to an IV tubing with injection port. The IV tubing is connected to a saline bag. Free-flowing access to the vein will be confirmed immediately prior to dose administration, and dose will be followed by saline flush.
干预措施: sugammadex (Drug)
结局指标
主要结局
Geometric Least Squares Mean Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. AUC0-last was determined by trapezoidal method. The reported least squares mean is the geometric least squares mean, which is the back-transformed least squares mean from the ANOVA linear fixed-effect model performed on natural log-transformed values of AUC0-last. This calculation also provides the associated 95% confidence interval.
Geometric Mean of Mean Residence Time (MRT) of Unchanged Drug in the Systemic Circulation Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. MRT is defined as the mean duration of time a drug molecule is present in the systemic circulation.
Geometric Mean Apparent Volume of Distribution Estimated at Steady-state (Vss) Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Vss is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state, calculated as CL\*MRT.
Geometric Mean Volume of Distribution During the Terminal Elimination Phase (Vz) Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Vz was calculated as Dose/(AUC0-∞\*λz).
Geometric Mean Percent of AUC0-∞ That Was Extrapolated (AUC%Extrap) Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. AUC%extrap represents the percentage of the AUC0-∞ obtained by extrapolation, calculated as (1 - \[AUC0-last/AUC0-∞\]) multiplied by 100.
Geometric Least Squares Mean Area Under the Plasma Drug Concentration-time Curve From Time Zero to Infinity (AUC0-∞) Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. AUC0-∞ was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC0-last, determined by trapezoidal method) and the extrapolated area given by Cest,last/λz, where Cest,last is the estimated concentration corresponding to the time of the last measurable concentration and λz is the apparent first-order terminal elimination rate constant. For each subject, λz was calculated by regression of the terminal log-linear portion of the plasma concentration-time profile. The reported least squares mean is the geometric least squares mean, which is the back-transformed least squares mean from the analysis of variance (ANOVA) linear fixed-effect model performed on natural log-transformed values of AUC0-∞. This calculation also provides the associated 95% confidence interval.
Geometric Least Squares Mean Maximum Observed Plasma Concentration (Cmax) Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Cmax was determined from the observed plasma concentration-time data. The reported least squares mean is the geometric least squares mean, which is the back-transformed least squares mean from the ANOVA linear fixed-effect model performed on natural log-transformed values of Cmax. This calculation also provides the associated 95% confidence interval.
Geometric Mean Total Clearance (CL) Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. CL is a quantitative measure of the rate at which a drug substance is removed from the body, calculated as Dose/AUC0-∞.
Median Time to Maximum Observed Plasma Concentration (Tmax) Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Tmax was determined from the observed plasma concentration-time data.
Median Time of the Last Measurable Plasma Concentration (Tlast) Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Tlast was determined from the observed plasma concentration-time data.
Geometric Mean Apparent First-order Terminal Elimination Half-life (t1/2) Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Elimination t1/2 is the time it takes for the concentration of the drug in the body to decrease by half during the elimination phase, calculated as the natural log of 2 (ln\[2\])/λz.
Geometric Mean Effective Half-life (t1/2eff) Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. t½eff was calculated as ln(2)\*MRT.
Geometric Mean Apparent First-order Terminal Elimination Rate Constant (λz) Following a Single IV Dose of Sugammadex
时间窗: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. λz was calculated by regression of the terminal log-linear portion of the plasma concentration-time profile.
次要结局
未报告次要终点