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

Hepatic Insufficiency Clinical Trial

Official title:

An Open-Label Study to Investigate the Single-Dose Pharmacokinetics of MK-3866 When Administered to Subjects With Moderate and Severe Hepatic Impairment

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03295266
• Other study ID #: 3866-006
• Secondary ID: MK-3866-006
• Status: Terminated
• Phase: Phase 1
• Start date: December 19, 2017
• Est. completion date: March 15, 2018

Study information

• Verified date: October 2019
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: March 15, 2018
• Est. primary completion date: March 15, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• Has taken amiodarone at any time in their life

Related Conditions & MeSH terms

• Antibacterial Agents
• Hepatic Insufficiency
• Liver Failure

Intervention

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

Locations

Country	Name	City	State
United States	Clinical Pharmacology of Miami ( Site 0001)	Hialeah	Florida
United States	Orlando Clinical Research Center ( Site 0002)	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration-time Curve of MK-3866 From Time 0 to Infinity (AUC0-8)	AUC0-8 is determined for the period up to 72 hours post-single dose. AUC0-8 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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Fraction of Dose of MK-3866 Excreted Unchanged in Urine (Fe)	Fe is the amount of drug excreted unchanged in urine. Urine samples were collected in 4-hour intervals up to 24 hours post-dose. The study terminated prior to analysis of urine samples and therefore no data are available.	Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose
Secondary	Renal Clearance (CLr) of MK-3866	CLr is the volume of plasma from which the study drug is completely removed per unit time by the kidney (i.e., excreted into the urine). Urine samples are collected in 4-hour intervals up to 24 hours post-dose. The study terminated prior to analysis of urine samples and therefore no data are available.	Predose, then pooled in the following increments: 0-4, 4-8, 8-12, 12-24 hours postdose
Secondary	Number of Participants With at Least One Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	Up to 14 days
Secondary	Number of Participants Who Discontinued the Study Due to an AE	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	Up to 14 days