Single-Dose Pharmacokinetics of MK-3866 in Participants With Hepatic Impairment (MK-3866-006)

NCT03295266 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 3866-006MK-3866-006
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, single-dose, Phase 1 study to evaluate the pharmacokinetics (PK) of intravenous (IV) MK-3866 in participants with moderate and severe hepatic impairment (HI) compared to that of matched healthy participants. The primary purpose of this study is to understand the effect of HI on the plasma PK of MK-3866 in order to guide dosing recommendations for participants with HI. This study will also evaluate the safety and tolerability of MK-3866 in participants with moderate and severe HI.

Conditions

Hepatic Insufficiency; Antibacterial Agents

Outcome Measures

Primary Outcomes (8)

• Area Under the Concentration-time Curve of MK-3866 From Time 0 to Infinity (AUC0-∞)

  AUC0-∞ is determined for the period up to 72 hours post-single dose. AUC0-∞ is an estimate of total plasma exposure from dosing to (extrapolated) infinity.

  Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

• Area Under the Concentration-time Curve of MK-3866 From Time 0 to Last Quantifiable Concentration (AUC0-last)

  AUC0-last is determined for the period up to 72 hours post-single dose. AUC0-last is an estimate of total plasma exposure from dosing to the time of last measurable sample.

  Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

• Area Under the Concentration-time Curve of MK-3866 From Time 0 to 24 Hours (AUC0-24hr)

  AUC0-24 is determined for the period up to 24 hours post-single dose. AUC0-24 is an estimate of total daily plasma exposure from dosing to 24 hours postdose.

  Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours postdose

• Concentration at the End of Infusion (Ceoi) of MK-3866

  The plasma sample collected at end-of-infusion (0.5 hours postdose) was used to determine Ceoi.

  0.5 (end of infusion) hours postdose

• Time to Maximum Concentration (Tmax) of MK-3866

  Tmax is the time at which the maximum plasma drug concentration is detected.

  Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

• Apparent Terminal Half-life (t1/2) of MK-3866

  Apparent t1/2 is the elimination half-life of MK-3866 from plasma.

  Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

• Clearance (CL) of MK-3866

  CL is the volume of plasma from which the study drug is completely removed per unit time.

  Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

• Volume of Distribution (Vz) of MK-3866

  Vz is the apparent volume of distribution during the terminal phase.

  Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 48, and 72 hours postdose

Secondary Outcomes (4)

• Fraction of Dose of MK-3866 Excreted Unchanged in Urine (Fe)

  Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose

• Renal Clearance (CLr) of MK-3866

  Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose

• Number of Participants With at Least One Adverse Event (AE)

  Up to 14 days

• Number of Participants Who Discontinued the Study Due to an AE

  Up to 14 days

Study Arms (3)

Moderate Hepatic Impairment (Panel A)

EXPERIMENTAL

Participants with moderate HI (estimated glomerular filtration rate \[eGFR\] of ≤60mL/min/1.73m\^2) receive a single IV dose of MK-3866 (150 mg) on Day 1.

Drug: MK-3866

Severe Hepatic Impairment (Panel B)

EXPERIMENTAL

Participants with severe HI (eGFR of ≤50 mL/min/1.73m\^2) receive a single IV dose of MK-3866 (150 mg) on Day 1.

Drug: MK-3866

Healthy Matched Controls (Panel C)

EXPERIMENTAL

Healthy participants receive a single IV dose of MK-3866 (150 mg) on Day 1.

Drug: MK-3866

Interventions

MK-3866 DRUG

Single IV infusion of MK-3866 150 mg administered over 30 minutes at Hour 0 on Day 1 of treatment period.

Healthy Matched Controls (Panel C); Moderate Hepatic Impairment (Panel A); Severe Hepatic Impairment (Panel B)

Eligibility Criteria

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

You may qualify if:

• Body mass index ≥19 \& ≤40 kg/m\^2
• Continuous non-smoker prior to screening \& enrollment
• HI Participants: Baseline health judged to be stable based on medical history (except for the HI condition), physical examination, vital signs, electrocardiograms, \& laboratory safety tests
• Healthy control participants: Is medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms
• HI Participants: Diagnosis of chronic (\>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) HI with features of cirrhosis
• HI Participants - Panel A (moderate HI) only: score on the Child-Pugh scale from 7 to 9 (moderate HI). At least 3 participants must have a score of 2 or higher on at least one of the laboratory parameters (i.e., albumin, international normalized ratio, and/or bilirubin) on the Child-Pugh scale
• HI Participants - Panel B (severe HI) only: Score on the Child-Pugh scale from 10 to 15 (severe HI)
• Is completely informed of the unknown risks of pregnancy \& agrees not to become pregnant or father a child during time in study
• For a female of childbearing potential: is either sexually inactive (abstinent) for 14 days prior to dosing \& throughout the study or is using an acceptable birth control method
• Non-vasectomized male: Participants must agree to use a condom with spermicide or abstain from sexual intercourse from dosing until 90 days after dosing

You may not qualify if:

• Mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study
• Has a history or presence of clinically significant medical or psychiatric condition or disease (other than HI - Panels A \& B) that might confound the results of the study or poses an additional risk to the participant. Remote history of cholecystectomy that is not an active issue may be included.
• Panels A \& B: Has a clinically significant history of cancer. Remote history with full cure or limited disease with complete resection (cure) may be included
• Has a history of drug/alcohol abuse within the past 6 months prior to dosing (Panels A \& B) or within the past 2 years prior to dosing (Panel C \[Healthy controls\])
• Panels A \& B: Consumes more than 3 glasses of alcoholic beverages (1 glass approximately equivalent to: beer \[354 mL/12 ounces\], wine \[118 mL/4 ounces\], or distilled spirits \[29.5 mL/1 ounce\]) per day, within 6 months of screening. Participants that consume 4 glasses of alcoholic beverages/day may be enrolled
• Panels A \& B: Consumes excessive amounts, defined as more than 6 servings (1 serving approximately equivalent to 120 mg of caffeine), of coffee, tea, cola, energy-drinks, or other caffeinated beverages/day
• Panels A \& B: Has a history of a liver transplant
• Has a history or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds
• Has moderate or severe renal insufficiency (estimated glomerular filtration rate of ≤60 mL/min/1.73 m2 for moderate HI or healthy control participants or ≤50 mL/min/1.73 m2 for severe HI participants)
• Panel C: Has positive macroscopic urine protein at screening (trace protein by dipstick allowed)
• Is a female participant who is pregnant or lactating
• Has positive results for the urine or breath alcohol screen and/or urine drug screen at screening
• Has positive results at screening for human immunodeficiency virus (HIV) (Panels A \& B) or for HIV, HBsAg, or hepatitis C virus (HCV) (Panel C)
• Panels A \& B: Participants with active HCV infection or hepatitis B virus (HBV) infection. Participants with prior/inactive HCV infection or past HBV infection may be enrolled.
• Is unable to refrain from or anticipates use of any medication or substance prohibited in study

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

Hepatic Insufficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System 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: September 25, 2017
• First Posted: September 27, 2017
• Study Start: December 19, 2017
• Primary Completion: March 15, 2018
• Study Completion: March 15, 2018
• Last Updated: November 13, 2019
• Results First Posted: November 13, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share

Locations

US (2)