Hepatitis C, Chronic
Conditions
Brief summary
This is a study to determine the pharmacokinetics (PK) and weight-based dose of boceprevir following single oral dose administration in Chronic Hepatitis C Virus (HCV) pediatric participants.
Interventions
DRUGBoceprevir
Single dose of boceprevir powder prior to breakfast in a dosing vehicle of chocolate pudding (i.e., a mousse or custard), apple sauce, Nutella, fruit pudding such as strawberry, cherry, or raspberry pudding, or yogurt or a similar semi-solid product into which the boceprevir powder can be evenly stirred
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Documented chronic hepatitis C (CHC) genotype 1 infection * Treatment naïve or failed previous interferon/ribavirin therapy (≥12 uninterrupted weeks) * Weigh between 10 kg to 90 kg inclusive at screening and baseline (Day -1). * Body Mass Index (BMI) from the 5th to the 95th percentile for the participant's age and gender, inclusive, per tables from the Center for Disease Control and Prevention, USA * Use of acceptable methods of contraception for at least 3 months prior to baseline and continue on study
Exclusion criteria
* Co-infection with the human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive). * Treatment with ribavirin within 90 days, or any interferon-alfa within 30 days * Discontinued from interferon treatment due to adverse events * Currently receiving antiviral/immunomodulating therapy for hepatitis C * Prior treatment with an HCV protease inhibitor * Prior treatment with any known hepatotoxic agent (including herbal remedies) * Use of investigational drugs within 30 days of enrollment into study * Evidence of de-compensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy. * Substance abuse (including but not limited to alcohol abuse, illicit drugs, inhalational drugs, marijuana use, etc) any time prior to entry into the study * Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. * Pregnant or breastfeeding female * Meeting any of the laboratory
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Time Curve (AUC) From 0-Infinity of Single Dose Boceprevir | 0 (pre-dose), 0.5, 1, 2, 2.5, 4.5, 5.5, 8, and 10 hours post dose | Plasma concentrations of boceprevir were determined at 0 (pre-dose), 0.5, 1, 2, 2.5, 4.5, 5.5, 8, and 10 hours post dose. |
| Maximum Plasma Concentration (Cmax) of Single Dose Boceprevir | 0 (pre-dose), 0.5, 1, 2, 2.5, 4.5, 5.5, 8, and 10 hours post dose | The maximum observed plasma concentration of boceprevir across sampling intervals was determined. |
| Time of Maximum Plasma Concentration (Tmax) of Single Dose Boceprevir | 0 (pre-dose), 0.5, 1, 2, 2.5, 4.5, 5.5, 8, and 10 hours post dose | The time at which the maximum plasma boceprevir concentration was observed. |
| Final Dose of Boceprevir By Age Group | Day 1 | — |
Participant flow
Pre-assignment details
This study originally intended to enroll 3 age-based pediatric cohorts. However the study was terminated after the completion of Cohort 1. No participants were enrolled in either Cohorts 2 or 3. Only data from Cohort 1 was collected.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Children 17 to ≥13 Years Participants were administered a single dose of boceprevir powder mixed in a suitable vehicle such pudding or applesauce. The first 4 participants were treated with a 11.4 mg/kg dose of boceprevir powder. The dose/weight ratio may be adjusted for the next 12 participants based on the evaluation of the PK, safety, and tolerability data from the first 4 participants. | 16 |
| Cohort 2: Children <13 to ≥7 Years Participants were administered a single dose of boceprevir powder mixed in a suitable vehicle such as pudding or applesauce. The first 4 participants were treated with boceprevir at a dose contingent on the PK and safety results in Cohort 1. The dose/weight ratio may be adjusted for the next 12 participants based on the evaluation of the PK, safety, and tolerability data from the first 4 participants. | 0 |
| Cohort 3: Children <7 to ≥3 Years Participants were administered a single dose of boceprevir powder mixed in a suitable vehicle such as pudding or applesauce. The first 4 participants were treated with boceprevir at a dose contingent on the PK and safety results in Cohort 2. The dose/weight ratio may be adjusted for the next 12 participants based on the evaluation of the PK, safety, and tolerability data from the first 4 participants. | 0 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Full dose not consumed. | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: Children 17 to ≥13 Years | Total |
|---|---|---|
| Age, Continuous Age | 14.9 Years STANDARD_DEVIATION 1.2 | 14.9 Years STANDARD_DEVIATION 1.2 |
| Sex: Female, Male Female | 7 Participants | 7 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 16 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 1 / 16 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Area Under the Plasma Concentration Time Curve (AUC) From 0-Infinity of Single Dose Boceprevir
Plasma concentrations of boceprevir were determined at 0 (pre-dose), 0.5, 1, 2, 2.5, 4.5, 5.5, 8, and 10 hours post dose.
Time frame: 0 (pre-dose), 0.5, 1, 2, 2.5, 4.5, 5.5, 8, and 10 hours post dose
Population: The Per Protocol (PP) population includes all participants who complied with the protocol sufficiently to ensure that data for this assessment were likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1: Children 17 to ≥13 Years | Area Under the Plasma Concentration Time Curve (AUC) From 0-Infinity of Single Dose Boceprevir | 6660 ng hr/mL |
Primary
Final Dose of Boceprevir By Age Group
Time frame: Day 1
Population: This outcome measure could not be analyzed due to termination of the study prior to enrolling Cohorts 2 and 3.
Primary
Maximum Plasma Concentration (Cmax) of Single Dose Boceprevir
The maximum observed plasma concentration of boceprevir across sampling intervals was determined.
Time frame: 0 (pre-dose), 0.5, 1, 2, 2.5, 4.5, 5.5, 8, and 10 hours post dose
Population: The Per Protocol (PP) population includes all participants who complied with the protocol sufficiently to ensure that data for this assessment were likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1: Children 17 to ≥13 Years | Maximum Plasma Concentration (Cmax) of Single Dose Boceprevir | 1710 ng/mL |
Primary
Time of Maximum Plasma Concentration (Tmax) of Single Dose Boceprevir
The time at which the maximum plasma boceprevir concentration was observed.
Time frame: 0 (pre-dose), 0.5, 1, 2, 2.5, 4.5, 5.5, 8, and 10 hours post dose
Population: The Per Protocol (PP) population includes all participants who complied with the protocol sufficiently to ensure that data for this assessment were likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1: Children 17 to ≥13 Years | Time of Maximum Plasma Concentration (Tmax) of Single Dose Boceprevir | 1.87 Hour |