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

NCT ID: NCT01797536

Last Updated: 2018-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-06
• Study Completion Date: 2014-08-20

Brief Summary

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.

Conditions

Hepatic Insufficiency

Study Design

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

Study Groups

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

Group Type: EXPERIMENTAL

Elbasvir

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Elbasvir

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Elbasvir

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Elbasvir

Intervention Type: DRUG

Interventions

Elbasvir

Intervention Type: DRUG

Eligibility Criteria

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

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

Sponsors

Celerion

INDUSTRY

Sponsor Role: collaborator

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

Call for Information (Investigational Site 0003)

Miami, Florida, United States

Call for Information (Investigational Site 0001)

Orlando, Florida, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 29247332 (View on PubMed)

Other Identifiers

8742-009

Identifier Type: -

Identifier Source: org_study_id