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

Phase 1
Completed
Conditions
Hepatitis C
Interventions
Registration Number
NCT01010906
Lead Sponsor
Merck Sharp & Dohme LLC
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Mild Hepatic Insufficiency (HI)Vaniprevir 300 mgParticipants with mild hepatic insufficiency (HI) administered a single 300 mg oral tablet of vaniprevir
Healthy Control to Mild HIVaniprevir 300 mgHealthy, matched to mild HI, control participants administered a single 300 mg oral tablet of vaniprevir
Moderate HIVaniprevir 300 mgParticipants with moderate HI administered a single 300 mg oral tablet of vaniprevir
Healthy Control to Moderate HIVaniprevir 300 mgHealthy, matched to moderate HI, control participants administered a single 300 mg oral tablet of vaniprevir
Severe HIVaniprevir 200 mgParticipants with severe HI administered a single 200 mg oral tablet of vaniprevir
Healthy Control to Severe HIVaniprevir 200 mgHealthy, matched to severe HI, control participants administered a single 200 mg oral tablet of vaniprevir
Primary Outcome Measures
NameTimeMethod
Area Under the Curve (AUC) (0-infinity) of Vaniprevir in Blood Plasma Following Single Dose Administration0-48 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
NameTimeMethod
Maximum Concentration (Cmax) of Vaniprevir in Blood Plasma Following Single Dose Administration0-48 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.

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