Pharmacokinetics (PK) and Safety of a Single Intravenous (IV) Dose of MK-3866 in Participants With Impaired Renal Function and in Healthy Controls (MK-3866-005)

NCT ID: NCT03259087

Last Updated: 2019-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-01
• Study Completion Date: 2018-02-09

Brief Summary

The purpose of this study is to compare plasma and urine PK parameters of MK-3866 between participants with impaired renal function and healthy control participants, to investigate the extent to which MK-3866 is removed from the plasma by hemodialysis (HD), and evaluate the safety and tolerability of MK-3866 in participants with impaired renal function.

Detailed Description

This is an open-label, 2-part single dose study: Part 1 will include participants with mild, moderate, and severe renal impairment (as well as healthy control participants), and Part 2 will include participants with end stage renal disease (ESRD) undergoing HD. Participants in Part 1 will receive a single IV dose of MK-3866, and plasma and urine samples will be collected over pre-specified time intervals. Participants in Part 2 will receive a single IV dose of MK-3866 on two separate occasions: in Period 1 immediately following their normally-scheduled HD, and in Period 2 approximately 30 minutes prior to their normally-scheduled HD. Plasma, urine, and dialysate samples will be collected over pre-specified time intervals for Part 2.

Conditions

Renal Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Mild Renal Impairment

Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.

Group Type: EXPERIMENTAL

MK-3866

Intervention Type: DRUG

Single IV infusion of 200 mg administered over 30 minutes (±5 minutes) on Day 1 of each treatment period.

Part 1: Moderate Renal Impairment

Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.

Group Type: EXPERIMENTAL

MK-3866

Intervention Type: DRUG

Single IV infusion of 200 mg administered over 30 minutes (±5 minutes) on Day 1 of each treatment period.

Part 1: Severe Renal Impairment

Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.

Group Type: EXPERIMENTAL

MK-3866

Intervention Type: DRUG

Single IV infusion of 200 mg administered over 30 minutes (±5 minutes) on Day 1 of each treatment period.

Part 1: Healthy Participants

Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.

Group Type: EXPERIMENTAL

MK-3866

Intervention Type: DRUG

Single IV infusion of 200 mg administered over 30 minutes (±5 minutes) on Day 1 of each treatment period.

Part 2: End-stage Renal Disease Undergoing Hemodialysis

End-stage renal disease (ESRD) participants received a single IV infusion of MK-3886 200 mg over 30 minutes on Day 1 just after hemodialysis (HD) in Period 1 and just before HD in Period 2. There was a washout of at least 6 days before dosing in Period 2.

Group Type: EXPERIMENTAL

MK-3866

Intervention Type: DRUG

Single IV infusion of 200 mg administered over 30 minutes (±5 minutes) on Day 1 of each treatment period.

Interventions

MK-3866

Single IV infusion of 200 mg administered over 30 minutes (±5 minutes) on Day 1 of each treatment period.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Females of non-childbearing potential. Male participants with female partner(s) of child-bearing potential agree to use a medically acceptable method of contraception during the study and for 90 days after dosing. If partner is pregnant, males agree to use a condom; if partner is of child-bearing potential, partner must use additional birth control
• Male participants agree not to donate sperm from the first dose until 90 days after dosing
• Adequate venous access

Renal Impaired Participants

• Liver function tests (serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and serum bilirubin (total and direct) within upper limit of normal
• Panels A, B, and C: no clinically significant change in renal status at least 1 month prior to dosing and not currently or previously been on hemodialysis
• Panel E only: ESRD maintained on stable regimen of at least 3 times per week HD for at least 3 months prior to first dosing

Healthy Participants

• Age within ± 15 years of the mean age of participants with impaired renal function to which the healthy participant is matched
• Medically healthy as per medical history, physical examination, vital signs, 12-lead electrocardiograms (ECGs), and clinical laboratory safety tests
• Blood urea nitrogen, liver function tests (ALT, AST, alkaline phosphatase [ALP]), and serum bilirubin (total and direct) within upper limit of normal.

Exclusion Criteria

• Mentally/legally incapacitated, or significant emotional problems or significant psychiatric disorder
• History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, respiratory, genitourinary or major neurological abnormalities or diseases
• History of any illness that might confound the results of the study or poses an additional risk to the participant by their participation in the study
• Clinically significant history of cancer
• Smoker and/or has used nicotine or nicotine-containing products within 3 months prior to screening
• Female participants of childbearing potential, pregnant, or lactating
• Positive results for urine or saliva drug screen and/or urine or breath alcohol screen at screening or check-in
• Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)
• Consumes more than 3 glasses of alcoholic beverages within 6 months of screening
• Consumes excessive amounts of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day
• Major surgery, donated or lost 1 unit of blood within 4 weeks prior to screening, or donated plasma within 7 days prior to dosing in Part 1 or first dose in Part 2

Renal Impaired Participants

• Panels A, B, and C: Failed renal transplant or has had nephrectomy
• Panels A, B, and C: Rapidly fluctuating renal function, as determined by historical measurements; or demonstrated/suspected renal artery stenosis
• Panel E only: Has required frequent emergent HD (≥3) within a year prior to first dosing

Healthy Participants

• Renal transplant or nephrectomy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Clinical Pharmacology of Miami ( Site 0001)

Hialeah, Florida, United States

Orlando Clinical Research Center ( Site 0002)

Orlando, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CA22640

Identifier Type: OTHER

Identifier Source: secondary_id

MK-3866-005

Identifier Type: OTHER

Identifier Source: secondary_id

3866-005

Identifier Type: -

Identifier Source: org_study_id