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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Vaniprevir 300 mg
* Drug: Vaniprevir 200 mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |