Phase 1 N=24 Treatment

Pharmacokinetics of Sugammadex (MK-8616) in Participants With Moderate and Severe Renal Insufficiency (MK-8616-105)

Renal Insufficiency · Renal Impairment

Bottom Line

View on ClinicalTrials.gov: NCT02011490 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Feb 2015

Primary outcome: Primary: 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 — 339; 151; 62.5 ug*hr/mL

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: sugammadex (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Merck Sharp & Dohme LLC
Primary completion: Jun 2014

Outcome Measures

Outcome	Result	p-value
PRIMARY 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	339; 151; 62.5	—
PRIMARY 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	335; 148; 61.1	—
PRIMARY Geometric Least Squares Mean Maximum Observed Plasma Concentration (Cmax) Following a Single IV Dose of Sugammadex	62.2; 60.6; 66.1	—
PRIMARY Geometric Mean Percent of AUC0-∞ That Was Extrapolated (AUC%Extrap) Following a Single IV Dose of Sugammadex	0.850; 2.14; 2.10	—
PRIMARY Geometric Mean Total Clearance (CL) Following a Single IV Dose of Sugammadex	0.961; 2.27; 5.70	—
PRIMARY Geometric Mean Volume of Distribution During the Terminal Elimination Phase (Vz) Following a Single IV Dose of Sugammadex	18.3; 18.8; 20.4	—
PRIMARY Geometric Mean of Mean Residence Time (MRT) of Unchanged Drug in the Systemic Circulation Following a Single IV Dose of Sugammadex	15.7; 7.02; 2.48	—
PRIMARY Geometric Mean Apparent Volume of Distribution Estimated at Steady-state (Vss) Following a Single IV Dose of Sugammadex	15.1; 15.9; 14.1	—
PRIMARY Median Time to Maximum Observed Plasma Concentration (Tmax) Following a Single IV Dose of Sugammadex	0.03; 0.03; 0.03	—
PRIMARY Median Time of the Last Measurable Plasma Concentration (Tlast) Following a Single IV Dose of Sugammadex	72.00; 24.00; 12.00	—
PRIMARY Geometric Mean Apparent First-order Terminal Elimination Half-life (t1/2) Following a Single IV Dose of Sugammadex	13.24; 5.73; 2.47	—
PRIMARY Geometric Mean Effective Half-life (t1/2eff) Following a Single IV Dose of Sugammadex	10.89; 4.87; 1.72	—
PRIMARY Geometric Mean Apparent First-order Terminal Elimination Rate Constant (λz) Following a Single IV Dose of Sugammadex	0.0524; 0.121; 0.280	—

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.

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02011490). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.