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

• ClinicalTrials.gov Identifier: NCT01010906
• Recruitment Status: Completed
• First Posted: November 10, 2009
• Results First Posted: September 29, 2014
• Last Update Posted: October 9, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis C	Drug: Vaniprevir 300 mg; Drug: Vaniprevir 200 mg	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, 3-Part, Single-Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of MK-7009
• Actual Study Start Date: July 1, 2009
• Actual Primary Completion Date: June 11, 2010
• Actual Study Completion Date: June 21, 2010

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: MK-7009

Outcome Measures

Primary Outcome Measures :

1. Area Under the Curve (AUC) (0-infinity) of Vaniprevir in Blood Plasma Following Single Dose Administration [ Time Frame: 0-48 hours postdose ]
   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.

Secondary Outcome Measures :

1. Maximum Concentration (Cmax) of Vaniprevir in Blood Plasma Following Single Dose Administration [ Time Frame: 0-48 hours postdose ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

Study Data/Documents: CSR Synopsis 

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT01010906 History of Changes
• Other Study ID Numbers: 7009-005; 2009_674
• First Posted: November 10, 2009
• Results First Posted: September 29, 2014
• Last Update Posted: October 9, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Additional relevant MeSH terms:

Hepatitis C; Hepatic Insufficiency; Liver Failure; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections