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

Hepatic Insufficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01797536
• Other study ID #: 8742-009
• Status: Completed
• Phase: Phase 1
• Start date: March 6, 2013
• Est. completion date: August 20, 2014

Study information

• Verified date: September 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: August 20, 2014
• Est. primary completion date: August 20, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatic Insufficiency

Intervention

Drug:
• Elbasvir

Locations

Country	Name	City	State
United States	Call for Information (Investigational Site 0003)	Miami	Florida
United States	Call for Information (Investigational Site 0001)	Orlando	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	Celerion

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Hepa — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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