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

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01425190
• Collaborator: (none)
• Enrollment: 16
• Arms: 3
• Actual Duration (Months): 14.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: Boceprevir	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessment of the Pharmacokinetics of Boceprevir in Pediatric Subjects With Chronic Hepatitis C Genotype 1 (Phase 1b); Protocol No. P07614
• Actual Study Start Date: Jan 4, 2012
• Actual Primary Completion Date: Mar 20, 2013
• Actual Study Completion Date: Mar 20, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. Final Dose of Boceprevir By Age Group [Day 1]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts 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 exclusion criteria

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01425190
• Other Study ID Numbers: P07614; 2010-023498-20; MK-3034-063
• First Posted: Aug 29, 2011
• Last Update Posted: Sep 11, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Cohort 1: Children 17 to ≥13 Years	Cohort 2: Children <13 to ≥7 Years	Cohort 3: Children <7 to ≥3 Years
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	16	0	0
COMPLETED	15	0	0
NOT COMPLETED	1	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1: Children 17 to ≥13 Years	Cohort 2: Children <13 to ≥7 Years	Cohort 3: Children <7 to ≥3 Years	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	16	0	0	16
Age (Years) [Mean (Standard Deviation) ]
Age	14.9 (1.2)	14.9 (1.2)
Sex: Female, Male (Count of Participants)
Female	7 43.8%	7 Infinity
Male	9 56.3%	9 Infinity

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration Time Curve (AUC) From 0-Infinity of Single Dose Boceprevir
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort 1: Children 17 to ≥13 Years	Cohort 2: Children <13 to ≥7 Years	Cohort 3: Children <7 to ≥3 Years
Arm/Group Description	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.	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.	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.
Measure Participants	14	0	0
Mean (Full Range) [ng hr/mL]	6660

2. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) of Single Dose Boceprevir
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort 1: Children 17 to ≥13 Years	Cohort 2: Children <13 to ≥7 Years	Cohort 3: Children <7 to ≥3 Years
Arm/Group Description	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.	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.	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.
Measure Participants	15	0	0
Mean (Full Range) [ng/mL]	1710

3. Primary Outcome

Title	Time of Maximum Plasma Concentration (Tmax) of Single Dose Boceprevir
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort 1: Children 17 to ≥13 Years	Cohort 2: Children <13 to ≥7 Years	Cohort 3: Children <7 to ≥3 Years
Arm/Group Description	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.	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.	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.
Measure Participants	15	0	0
Mean (Full Range) [Hour]	1.87

4. Primary Outcome

Title	Final Dose of Boceprevir By Age Group
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

This outcome measure could not be analyzed due to termination of the study prior to enrolling Cohorts 2 and 3.

Arm/Group Title	Cohort 1: Children 17 to ≥13 Years	Cohort 2: Children <13 to ≥7 Years	Cohort 3: Children <7 to ≥3 Years
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

Adverse Events

Time Frame	Nonserious adverse events (AEs) and serious AEs (SAEs) were collected during the time of boceprevir administration until the final PK sample was collected on Day 1.
Adverse Event Reporting Description	AEs were monitored in the All Subjects as Treated (all boceprevir-treated participants) population.
Arm/Group Title	Cohort 1: Children 17 to ≥13 Years		Cohort 2: Children <13 to ≥7 Years		Cohort 3: Children <7 to ≥3 Years
Arm/Group Description	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.		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.		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.
All Cause Mortality
	Cohort 1: Children 17 to ≥13 Years		Cohort 2: Children <13 to ≥7 Years		Cohort 3: Children <7 to ≥3 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1: Children 17 to ≥13 Years		Cohort 2: Children <13 to ≥7 Years		Cohort 3: Children <7 to ≥3 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		0/0 (NaN)		0/0 (NaN)
Investigations
Alanine aminotransferase increased	1/16 (6.3%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Liver function test abnormal	1/16 (6.3%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Other (Not Including Serious) Adverse Events
	Cohort 1: Children 17 to ≥13 Years		Cohort 2: Children <13 to ≥7 Years		Cohort 3: Children <7 to ≥3 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/16 (37.5%)		0/0 (NaN)		0/0 (NaN)
Gastrointestinal disorders
Nausea	2/16 (12.5%)	2	0/0 (NaN)	0	0/0 (NaN)	0
General disorders
Asthenia	1/16 (6.3%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Malaise	1/16 (6.3%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Investigations
Blood pressure systolic increased	1/16 (6.3%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Hepatic enzyme increased	1/16 (6.3%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Nervous system disorders
Dysgeusia	1/16 (6.3%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Syncope	3/16 (18.8%)	3	0/0 (NaN)	0	0/0 (NaN)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The investigator agrees not to publish or publicly present any interim results of the trial without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication.