NCT Number: NCT01797536
The Influence of Hepatic Insufficiency on the Pharmacokinetics of Elbasvir (MK-8742) (MK-8742-009)
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.
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Age range
18 year–75 year
Sex eligibility
All sexes
Study type
Interventional
Phase
Phase 1
Primary location
Call for Information (Investigational Site 0003), Miami, Florida, United States
Who can participate
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
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
Treatment and study plan
Primary outcomes
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Area Under the Curve From 0 to Infinity (AUC0-inf) of Elbasvir
Time frame: Predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168
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.
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Area Under the Curve From 0 to 24 Hours (AUC0-24hr) of Elbasvir
Time frame: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, and 24
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.
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Maximum Concentration (Cmax) of Elbasvir
Time frame: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168
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.
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Concentration at 24 Hours (C24) After Dosing Elbasvir
Time frame: Hour 24
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.
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Time to Maximum Concentration (Tmax) of Elbasvir
Time frame: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168
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.
-
Apparent Terminal Half-Life (t1/2) of Elbasvir
Time frame: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168
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.
Sponsors and collaborators
Lead sponsor
Merck Sharp & Dohme LLC
Industry
Collaborators
- Celerion
Registry information
Official study title
A Three-Part, Open-Label, Single-Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of MK-8742
Important dates
- Study start
- 2013
- Primary completion
- 2014
- Study completion
- 2014
- First posted
- Feb 22, 2013
- Registry last updated
- Oct 25, 2018
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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