A Study Investigating the Influence of Hepatic Insufficiency on the Pharmacokinetics of Vaniprevir (MK-7009-005)

An Open-label, 3-Part, Single-Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of MK-7009

This was a 3-part study comparing the pharmacokinetics after administration of vaniprevir (MK-7009) for participants with mild, moderate or severe hepatic insufficiency with healthy matched control participants. The primary hypothesis is that the area under the curve (AUC) (0 to infinity) of vaniprevir for participants with mild, moderate, or severe hepatic insufficiency is similar to that observed in healthy matched controlled participants.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Vaniprevir 300 mg; Drug: Vaniprevir 200 mg

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Hepatic Participants:

• Females of reproductive potential test negative for pregnancy and agree to use an appropriate method of contraception during the study
• Apart from hepatic insufficiency, is in good general health
• Has a diagnosis of chronic stable hepatic insufficiency
• Score on the Child-Pugh scale ranged from 5 to 6 (mild hepatic insufficiency); from 7 to 9 (moderate hepatic insufficiency); from 10 to 15 (severe hepatic insufficiency). Moderate and Severe participants must have had a 50% score of 2 or higher on at least one of the laboratory parameters (i.e., albumin, prothrombin time, bilirubin) at the prestudy visit.

Healthy Matched Participants:

• Females of reproductive potential test negative for pregnancy and agree to use an appropriate method of contraception during the study
• Is in good health

Exclusion Criteria:

• Female is pregnant, lactating, expecting to become pregnant or donate eggs
• Has a history of stroke or seizures
• Has a history of cancer
• Is unable to refrain from the use of any prescription or non-prescription medication
• Consumes excessive amounts of alcohol or caffeinated beverages daily
• Has had surgery, donated blood or participated in another investigational study with in the last 4 weeks
• Is a regular user or past abuser of any illicit drug including alcohol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild Hepatic Insufficiency (HI); Participants with mild hepatic insufficiency (HI) administered a single 300 mg oral tablet of vaniprevir	Drug: Vaniprevir 300 mg; single dose administration of 300 mg oral tablet; Other Names: MK-7009
Experimental: Healthy Control to Mild HI; Healthy, matched to mild HI, control participants administered a single 300 mg oral tablet of vaniprevir	Drug: Vaniprevir 300 mg; single dose administration of 300 mg oral tablet; Other Names: MK-7009
Experimental: Moderate HI; Participants with moderate HI administered a single 300 mg oral tablet of vaniprevir	Drug: Vaniprevir 300 mg; single dose administration of 300 mg oral tablet; Other Names: MK-7009
Experimental: Healthy Control to Moderate HI; Healthy, matched to moderate HI, control participants administered a single 300 mg oral tablet of vaniprevir	Drug: Vaniprevir 300 mg; single dose administration of 300 mg oral tablet; Other Names: MK-7009
Experimental: Severe HI; Participants with severe HI administered a single 200 mg oral tablet of vaniprevir	Drug: Vaniprevir 200 mg; single dose administration of 200 mg oral tablet; Other Names: MK-7009
Experimental: Healthy Control to Severe HI; Healthy, matched to severe HI, control participants administered a single 200 mg oral tablet of vaniprevir	Drug: Vaniprevir 200 mg; single dose administration of 200 mg oral tablet; Other Names: MK-7009

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve (AUC) (0-infinity) of Vaniprevir in Blood Plasma Following Single Dose Administration	Participants were administered a single dose of vaniprevir; then their blood was collected at the following time points: 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 32 and 48 hours postdose. The AUC (0-infinity) of vaniprevir in blood plasma was based on an analysis of covariance (ANCOVA) model used to analyze natural log-transformed values that were back-transformed to derive geometric least-squares mean and confidence interval.	0-48 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration (Cmax) of Vaniprevir in Blood Plasma Following Single Dose Administration	Participants were administered a single dose of vaniprevir; then their blood was collected at the following time points: 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 32 and 48 hours postdose. The Cmax of vaniprevir in blood plasma was based on an ANCOVA model used to analyze natural log-transformed values that were back-transformed to derive geometric least-squares mean and confidence interval.	0-48 hours postdose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2009
• Primary Completion (Actual): June 11, 2010
• Study Completion (Actual): June 21, 2010

Study Registration Dates

• First Submitted: November 6, 2009
• First Submitted That Met QC Criteria: November 6, 2009
• First Posted (Estimate): November 10, 2009

Study Record Updates

• Last Update Posted (Actual): October 9, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Liver Failure; Hepatic Insufficiency; Hepatitis C
• Other Study ID Numbers: 7009-005; 2009_674

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis