Clinical trial NCT02011490: Pharmacokinetics of Sugammadex (MK-8616) in Participants With Moderate and Severe Renal Insufficiency (MK-8616-105)
Official title: An Open-Label, Single-Dose Study to Investigate the Pharmacokinetics of MK-8616 in Subjects With Moderate and Severe Renal Insufficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Insufficiency
Renal Impairment
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2013-12-13
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: In each study period (i.e., Part 1 and Part 2), day of drug administration was defined to be Day 1.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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 1. 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

Primary outcomes:
measure: 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
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Geometric Least Squares Mean Maximum Observed Plasma Concentration (Cmax) Following a Single IV Dose of Sugammadex
timeFrame: 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)
measure: Geometric Mean Percent of AUC0-∞ That Was Extrapolated (AUC%Extrap) Following a Single IV Dose of Sugammadex
timeFrame: 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)
measure: Geometric Mean Total Clearance (CL) Following a Single IV Dose of Sugammadex
timeFrame: 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)
measure: Geometric Mean Volume of Distribution During the Terminal Elimination Phase (Vz) Following a Single IV Dose of Sugammadex
timeFrame: 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)
measure: Geometric Mean of Mean Residence Time (MRT) of Unchanged Drug in the Systemic Circulation Following a Single IV Dose of Sugammadex
timeFrame: 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)
measure: Geometric Mean Apparent Volume of Distribution Estimated at Steady-state (Vss) Following a Single IV Dose of Sugammadex
timeFrame: 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)
measure: Median Time to Maximum Observed Plasma Concentration (Tmax) Following a Single IV Dose of Sugammadex
timeFrame: 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)
measure: Median Time of the Last Measurable Plasma Concentration (Tlast) Following a Single IV Dose of Sugammadex
timeFrame: 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)
measure: Geometric Mean Apparent First-order Terminal Elimination Half-life (t1/2) Following a Single IV Dose of Sugammadex
timeFrame: 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)
measure: Geometric Mean Effective Half-life (t1/2eff) Following a Single IV Dose of Sugammadex
timeFrame: 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)
measure: Geometric Mean Apparent First-order Terminal Elimination Rate Constant (λz) Following a Single IV Dose of Sugammadex
timeFrame: 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)
Secondary outcomes:
Other outcomes:
Locations:
city: Hialeah
country: United States
facility: Investigational Site 001
state: Florida
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Min KC, Lasseter KC, Marbury TC, Wrishko RE, Hanley WD, Wolford DG, Udo de Haes J, Reitmann C, Gutstein DE. Pharmacokinetics of sugammadex in subjects with moderate and severe renal impairment . Int J Clin Pharmacol Ther. 2017 Sep;55(9):746-752. doi: 10.5414/CP203025.