Pharmacokinetics of Boceprevir in Pediatric Subjects With Chronic Hepatitis C Genotype 1 (P07614)

Assessment of the Pharmacokinetics of Boceprevir in Pediatric Subjects With Chronic Hepatitis C Genotype 1 (Phase 1b); Protocol No. P07614

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.

Study Overview

• Status: Terminated
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: Boceprevir

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 exclusion criteria

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Boceprevir; 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; Other Names: SCH 503034
Experimental: 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.	Drug: Boceprevir; 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; Other Names: SCH 503034
Experimental: 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.	Drug: Boceprevir; 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; Other Names: SCH 503034

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	The maximum observed plasma concentration of boceprevir across sampling intervals was determined.	0 (pre-dose), 0.5, 1, 2, 2.5, 4.5, 5.5, 8, and 10 hours post dose
Time of Maximum Plasma Concentration (Tmax) of Single Dose Boceprevir	The time at which the maximum plasma boceprevir concentration was observed.	0 (pre-dose), 0.5, 1, 2, 2.5, 4.5, 5.5, 8, and 10 hours post dose
Final Dose of Boceprevir By Age Group		Day 1

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2012
• Primary Completion (Actual): March 20, 2013
• Study Completion (Actual): March 20, 2013

Study Registration Dates

• First Submitted: August 26, 2011
• First Submitted That Met QC Criteria: August 26, 2011
• First Posted (Estimate): August 29, 2011

Study Record Updates

• Last Update Posted (Actual): September 11, 2018
• Last Update Submitted That Met QC Criteria: August 13, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: P07614; 2010-023498-20 (EudraCT Number); MK-3034-063 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis