The Influence of Hepatic Insufficiency on the Pharmacokinetics of Elbasvir (MK-8742) (MK-8742-009)

A Three-Part, Open-Label, Single-Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of MK-8742

The purpose of this study is to evaluate the pharmacokinetics (PK) profile of elbasvir (MK-8742) after a single dose to participants with mild, moderate, or severe hepatic insufficiency compared with healthy controls.

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency
• Intervention / Treatment: Drug: Elbasvir

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Call for Information (Investigational Site 0003)
    • Orlando, Florida, United States, 32809
      • Call for Information (Investigational Site 0001)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body mass index (BMI) 19 - 40 kg/m^2, inclusive
• In good health based on medical history, physical examination, vital signs, and laboratory safety tests
• No clinically significant abnormality on electrocardiogram (ECG)
• For participants with hepatic insufficiency only, diagnosis of chronic (> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any cause
• For participants with hepatic insufficiency only, score on the Child-Pugh scale must range from 5 to 6 for mild hepatic insufficiency, from 7 to 9 for moderate hepatic insufficiency, and from 10 to 15 for severe hepatic insufficiency
• Females of childbearing potential must be either be sexually inactive (abstinent) for 14 days before study drug administration and throughout the study or be using an acceptable method of birth control
• Females of non-childbearing potential must have undergone sterilization procedures at least 6 months before Study Day 1
• Non-vasectomized males must agree to use a condom with spermicide or abstain from sexual intercourse during the study and for 3 months after study drug administration
• Ability to swallow multiple capsules

Exclusion Criteria:

• Previously enrolled in this study
• Mentally or legally incapacitated, significant emotional problems at the time of screening or expected during the conduct of the study, or a history of a clinically significant psychiatric disorder over the last 5 years
• History or presence of significant cardiovascular, pulmonary, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological disease
• History of any illness that might confound the results of the study or pose an additional risk to the participant by participating in the study
• For participants with hepatic insufficiency only, estimated creatinine clearance (CrCl) ≤30 mL/min based on the Cockcroft-Gault equation at screening
• History or presence of drug abuse within the past 2 years
• For healthy participants only, history of alcoholism within the past 2 years
• Females who are pregnant or lactating
• Positive results for the urine drug screen at screening or check-in
• Positive results at screening or history of human immunodeficiency virus (HIV) or untreated hepatitis C virus (HCV); HCV ribonucleic acid (RNA)-negative participants documented to be cured following anti-HCV treatment are eligible
• For healthy participants only, positive results at screening for hepatitis B surface antigen (HBsAg)
• Use of any drugs or substances known to be strong inhibitors of cytochrome P450 3A4 (CYP3A4) enzymes and/or P-glycoprotein (P-gp) or any inhibitors of organic anion transporting peptide 1B (OATP1B) within 14 days or 5-times the half-life of the product (for healthy participants) or which cannot be discontinued at least 14 days or 5 times the half-life of the product (for hepatic insufficiency participants) before study drug administration and throughout the study
• Use of any drugs or substances known to be strong inducers of CYP3A4 enzymes and/or P-gp, including St-John's Wort or rifampin, within 28 days or 5 times the half-life of the product before study drug administration
• Currently use of any medication or substance which cannot be discontinued or maintained at a steady dose and regimen at least 14 days before study drug administration and throughout the study
• For healthy participants only, on a special diet within 28 days before study drug administration
• Blood donation >500 mL or significant blood loss within 56 days before study drug administration
• Plasma donation within 7 days before study drug administration
• Participation in another clinical study within 28 days before study drug administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild Hepatic Insufficiency; Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with mild hepatic insufficiency, defined as a score of 5 to 6 on the Child-Pugh scale	Drug: Elbasvir
Experimental: Moderate Hepatic Insufficiency; Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with moderate hepatic insufficiency, defined as a score of 7 to 9 on the Child-Pugh scale	Drug: Elbasvir
Experimental: Severe Hepatic Insufficiency; Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with severe hepatic insufficiency, defined as a score of 10 to 15 on the Child-Pugh scale	Drug: Elbasvir
Experimental: Healthy Participants; Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants matched to the mean of all hepatic insufficiency participants for age, gender, and weight	Drug: Elbasvir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From 0 to Infinity (AUC0-inf) of Elbasvir	Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the AUC0-inf of elbasvir.	Predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168
Area Under the Curve From 0 to 24 Hours (AUC0-24hr) of Elbasvir	Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 to determine the AUC0-24hr of elbasvir.	Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, and 24
Maximum Concentration (Cmax) of Elbasvir	Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the Cmax of Elbasvir.	Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168
Concentration at 24 Hours (C24) After Dosing Elbasvir	Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24, to determine the concentration of elbasvir at Hour 24 was determined.	Hour 24
Time to Maximum Concentration (Tmax) of Elbasvir	Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the maximum concentration (Cmax) of elbasvir. The time to reach Cmax (Tmax) was determined.	Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168
Apparent Terminal Half-Life (t1/2) of Elbasvir	Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the t1/2 of elbasvir.	Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Celerion

Publications and helpful links

General Publications

• Marshall WL, Feng HP, Wenning L, Garrett G, Huang X, Liu F, Panebianco D, Caro L, Fandozzi C, Lasseter KC, Preston RA, Marbury T, Butterton JR, Iwamoto M, Yeh WW. Pharmacokinetics, Safety, and Tolerability of Single-Dose Elbasvir in Participants with Hepatic Impairment. Eur J Drug Metab Pharmacokinet. 2018 Jun;43(3):321-329. doi: 10.1007/s13318-017-0451-9.

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2013
• Primary Completion (Actual): August 20, 2014
• Study Completion (Actual): August 20, 2014

Study Registration Dates

• First Submitted: February 20, 2013
• First Submitted That Met QC Criteria: February 20, 2013
• First Posted (Estimate): February 22, 2013

Study Record Updates

• Last Update Posted (Actual): October 25, 2018
• Last Update Submitted That Met QC Criteria: September 27, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency
• Other Study ID Numbers: 8742-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf