Clinical trial NCT01797536: The Influence of Hepatic Insufficiency on the Pharmacokinetics of Elbasvir (MK-8742) (MK-8742-009)
Official title: A Three-Part, Open-Label, Single-Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of MK-8742
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Insufficiency
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Celerion
First posted: 2013-02-22
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Area Under the Curve From 0 to Infinity (AUC0-inf) of Elbasvir
timeFrame: Predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168
measure: Area Under the Curve From 0 to 24 Hours (AUC0-24hr) of Elbasvir
timeFrame: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, and 24
measure: Maximum Concentration (Cmax) of Elbasvir
timeFrame: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168
measure: Concentration at 24 Hours (C24) After Dosing Elbasvir
timeFrame: Hour 24
measure: Time to Maximum Concentration (Tmax) of Elbasvir
timeFrame: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168
measure: Apparent Terminal Half-Life (t1/2) of Elbasvir
timeFrame: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: Call for Information (Investigational Site 0003)
state: Florida
city: Orlando
country: United States
facility: Call for Information (Investigational Site 0001)
state: Florida
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.