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)

NCT03259087 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 3866-005CA22640MK-3866-005
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

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.

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (18)

• Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf)

  Plasma samples were collected at pre-specified time points and AUC0-inf was assessed. Plasma concentrations of MK-3866 were determined using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS).

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants

• Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to the Time of the Last Quantifiable Sample (AUC0-last)

  Plasma samples were collected at pre-specified time points and AUC0-last was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants

• Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to 24 Hours After Dosing (AUC0-24)

  Plasma samples were collected at pre-specified time points and AUC0-24 was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours after dosing on Day 1

• Part 1: Plasma Concentration of MK-3866 at the End of the Infusion (Ceoi)

  Plasma samples were collected at pre-specified time points and Ceoi was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS.

  At the end of the infusion (0.5 hours after infusion start) on Day 1

• Part 1: Maximum Plasma Concentration of MK-3866 (Cmax)

  Plasma samples were collected at pre-specified time points and Cmax was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants

• Part 1: Plasma Clearance of MK-3866 (CL)

  Plasma samples were collected at pre-specified time points and CL was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants

• Part 1: Time to Maximum Plasma Concentration of MK-3866 (Tmax)

  Plasma samples were collected at pre-specified time points and Tmax was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants

• Part 1: Elimination Terminal Half-life of Plasma MK-3866 (t1/2)

  Plasma samples were collected at pre-specified time points and t1/2 was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric % coefficient of variation (%CV).

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants

• Part 1: Volume of Distribution of Plasma MK-3866 (Vz)

  Plasma samples were collected at pre-specified time points and Vz was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants

• Part 2: AUC0-inf of Plasma MK-3866

  Plasma samples were collected at pre-specified time points and AUC0-inf was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2

• Part 2: AUC0-last of Plasma MK-3866

  Plasma samples were collected at pre-specified time points and AUC0-last was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2

• Part 2: AUC0-24 of Plasma MK-3866

  Plasma samples were collected at pre-specified time points and AUC0-24 was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2

• Part 2: Ceoi of Plasma MK-3866

  Plasma samples were collected at pre-specified time points and Ceoi was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.

  At the end of the infusion (0.5 hours after infusion start) on Day 1 of Period 1 and Period 2

• Part 2: Cmax of Plasma MK-3866

  Plasma samples were collected at pre-specified time points and Cmax was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2

• Part 2: CL of Plasma MK-3866

  Plasma samples were collected at pre-specified time points and CL was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2

• Part 2: Tmax of Plasma MK-3866

  Plasma samples were collected at pre-specified time points and Tmax was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2

• Part 2: t1/2 of Plasma MK-3866

  Plasma samples were collected at pre-specified time points and t1/2 was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. Method of dispersion used for these data is geometric %CV.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2

• Part 2: Vz of Plasma MK-3866

  Plasma samples were collected at pre-specified time points and Vz was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. Method of dispersion used for these data is geometric %CV.

  Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2

Secondary Outcomes (19)

• Part 1: Total Amount of MK-3866 Excreted in the Urine Over 24 Hours (Ae0-24)

  Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1

• Part 1: Renal Clearance (CLr) of MK-3866

  Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1

• Part 1: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24)

  Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1

• Part 2: Total Amount of MK-3866 Excreted Unchanged in the Urine Over the Period of 24 Hours (Ae0-24)

  Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1 of Period 1 and Period 2

• Part 2: Renal Clearance (CLr) of MK-3866

  Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1 of Period 1 and Period 2

Study Arms (5)

Part 1: Mild Renal Impairment

EXPERIMENTAL

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

Drug: MK-3866

Part 1: Moderate Renal Impairment

EXPERIMENTAL

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

Drug: MK-3866

Part 1: Severe Renal Impairment

EXPERIMENTAL

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

Drug: MK-3866

Part 1: Healthy Participants

EXPERIMENTAL

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

Drug: MK-3866

Part 2: End-stage Renal Disease Undergoing Hemodialysis

EXPERIMENTAL

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.

Drug: MK-3866

Interventions

MK-3866 DRUG

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

Part 1: Healthy Participants; Part 1: Mild Renal Impairment; Part 1: Moderate Renal Impairment; Part 1: Severe Renal Impairment; Part 2: End-stage Renal Disease Undergoing Hemodialysis

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Clinical Pharmacology of Miami ( Site 0001)

Hialeah, Florida, 33014, United States

Location

Orlando Clinical Research Center ( Site 0002)

Orlando, Florida, 32809, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2017
• First Posted: August 23, 2017
• Study Start: September 1, 2017
• Primary Completion: January 28, 2018
• Study Completion: February 9, 2018
• Last Updated: April 19, 2019
• Results First Posted: April 19, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share

Locations

US (2)