Hepatitis C
Conditions
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.
Interventions
single dose administration of 300 mg oral tablet
DRUGVaniprevir 200 mg
single dose administration of 200 mg oral tablet
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) (0-infinity) of Vaniprevir in Blood Plasma Following Single Dose Administration | 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
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) of Vaniprevir in Blood Plasma Following Single Dose Administration | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mild Hepatic Insufficiency (HI) Participants with mild hepatic insufficiency (HI) administered a single 300 mg oral tablet of vaniprevir | 10 |
| Healthy Control for Mild HI Healthy matched control participants administered a single 300 mg oral tablet of vaniprevir | 10 |
| Moderate HI Participants with moderate HI administered a single 300 mg oral tablet of vaniprevir | 10 |
| Healthy Control for Moderate HI Healthy matched control participants administered a single 300 mg oral tablet of vaniprevir | 10 |
| Severe HI Participants with severe HI administered a single 200 mg oral tablet of vaniprevir | 10 |
| Healthy Control for Severe HI Healthy matched control participants administered a single 200 mg oral tablet of vaniprevir | 10 |
| Total | 60 |
Baseline characteristics
| Characteristic | Mild Hepatic Insufficiency (HI) | Healthy Control for Mild HI | Moderate HI | Healthy Control for Moderate HI | Severe HI | Healthy Control for Severe HI | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.3 Years STANDARD_DEVIATION 5.03 | 52.1 Years STANDARD_DEVIATION 3.54 | 52.1 Years STANDARD_DEVIATION 6.51 | 53.3 Years STANDARD_DEVIATION 4.9 | 53.4 Years STANDARD_DEVIATION 6.08 | 52.6 Years STANDARD_DEVIATION 7.04 | 52.3 Years STANDARD_DEVIATION 5.49 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 9 Participants | 9 Participants | 6 Participants | 6 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 10 | 1 / 10 | 1 / 10 | 2 / 10 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
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.
Time frame: 0-48 hours postdose
Population: Participants administered at least one dose of investigational drug. AUC for one participant with Mild HI was not estimated due to poor correlation of the linear regression.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Mild Hepatic Insufficiency (HI) | Area Under the Curve (AUC) (0-infinity) of Vaniprevir in Blood Plasma Following Single Dose Administration | 2.68 µM.hr |
| Healthy Control for Mild HI | Area Under the Curve (AUC) (0-infinity) of Vaniprevir in Blood Plasma Following Single Dose Administration | 1.48 µM.hr |
| Moderate HI | Area Under the Curve (AUC) (0-infinity) of Vaniprevir in Blood Plasma Following Single Dose Administration | 5.09 µM.hr |
| Healthy Control for Moderate HI | Area Under the Curve (AUC) (0-infinity) of Vaniprevir in Blood Plasma Following Single Dose Administration | 1.64 µM.hr |
| Severe HI | Area Under the Curve (AUC) (0-infinity) of Vaniprevir in Blood Plasma Following Single Dose Administration | 7.79 µM.hr |
| Healthy Control for Severe HI | Area Under the Curve (AUC) (0-infinity) of Vaniprevir in Blood Plasma Following Single Dose Administration | 0.925 µM.hr |
90% CI: [0.96, 3.43]
90% CI: [1.6, 6.04]
90% CI: [5.2, 13.64]
Secondary
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.
Time frame: 0-48 hours postdose
Population: Participants administered at least one dose of investigational drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Mild Hepatic Insufficiency (HI) | Maximum Concentration (Cmax) of Vaniprevir in Blood Plasma Following Single Dose Administration | 0.922 µM |
| Healthy Control for Mild HI | Maximum Concentration (Cmax) of Vaniprevir in Blood Plasma Following Single Dose Administration | 0.586 µM |
| Moderate HI | Maximum Concentration (Cmax) of Vaniprevir in Blood Plasma Following Single Dose Administration | 1.88 µM |
| Healthy Control for Moderate HI | Maximum Concentration (Cmax) of Vaniprevir in Blood Plasma Following Single Dose Administration | 0.852 µM |
| Severe HI | Maximum Concentration (Cmax) of Vaniprevir in Blood Plasma Following Single Dose Administration | 2.06 µM |
| Healthy Control for Severe HI | Maximum Concentration (Cmax) of Vaniprevir in Blood Plasma Following Single Dose Administration | 0.335 µM |
90% CI: [0.76, 3.24]
90% CI: [1.21, 4.03]
90% CI: [3.9, 9.71]