The Influence of Hepatic Insufficiency on the Pharmacokin... | NCT01797536

NCT01797536

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Celerion	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Mild Hepatic Insufficiency	Experimental	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
Moderate Hepatic Insufficiency	Experimental	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
Severe Hepatic Insufficiency	Experimental	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
Healthy Participants	Experimental	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

Name	Type	Description	Arm Group Labels	Other Names
Elbasvir	Drug		Healthy Participants Mild Hepatic Insufficiency Moderate Hepatic Insufficiency Severe Hepatic Insufficiency

Outcomes Module

Primary Outcomes

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.

Eligibility Module

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

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Call for Information (Investigational Site 0003)		Miami	Florida	33136	United States
Call for Information (Investigational Site 0001)

PubMed Identifier	Type	Citation	Retractions
29247332	Result	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.

Arm/Group Information

ID	Title	Description
FG000	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
FG001	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
FG002	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
FG003	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

ID	Title	Description
BG000	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
BG001	Moderate Hepatic Insufficiency

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

Participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment and had available data for the endpoint. Moderate arm summary excludes data for 3 participants incorrectly re-enrolled and dosed in moderate arm after completing dosing and follow-up in the mild insufficiency arm.

Posted

Geometric Mean

95% Confidence Interval

μM•hr

Predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168

ID	Title	Description
OG000	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

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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

ID	Term
D008107	Liver Diseases
D004066	Digestive System Diseases