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A Study to Evaluate Aprepitant for the Prevention of Post-Operative Nausea and Vomiting in Children (MK-0869-219)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01732458
First received: November 19, 2012
Last updated: August 4, 2017
Last verified: August 2017
  Purpose

The purpose of this study is to evaluate the pharmacokinetics (PK), safety, and tolerability of aprepitant for the prevention of post-operative nausea and vomiting (PONV) in pediatric participants.

Post-operative aprepitant plasma concentrations will be evaluated with a non-compartmental analysis (NCA) at each dose and for each age cohort. Full PK profiles analyzed using population PK modeling and simulation will be described in a separate report.


Condition Intervention Phase
Post-operative Nausea Post-operative Vomiting Drug: Aprepitant Drug: Placebo to Aprepitant Drug: Ondansetron Drug: Placebo to match ondansetron Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:
This study will be conducted as a partially blinded study. PK samples will not be collected from participants in the control group. To maintain a partial blind, approximately 3 participants randomly selected from each age group in each of the aprepitant treatment groups will not have PK sampling. All participants will remain blinded to the study treatment. The investigator and Sponsor will be blinded to the study medication in participants not providing PK samples. The investigator and Sponsor will remain blinded to the aprepitant dose given to participants from whom PK samples will be collected.
Primary Purpose: Treatment
Official Title: A Phase IIb, Partially-Blinded, Randomized, Active Comparator-Controlled Study to Evaluate the Pharmacokinetics/Pharmacodynamics, Safety, and Tolerability of Aprepitant in Pediatric Patients for the Prevention of Post Operative Nausea and Vomiting

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Area Under the Concentration-time Curve of Aprepitant From Time 0 to the Last Measurable Concentration (AUC0-last) Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    AUC0-last was analyzed independently for participants in the 125 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using a noncompartmental analysis (NCA). The limit of quantitation (LOQ) value for this analysis was 10 ng/mL.

  • Maximum Concentration (Cmax) of Aprepitant Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Cmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Time to Maximum Concentration (Tmax) of Aprepitant Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Tmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    AUC0-last was analyzed independently for participants in the 125 mg dose equivalent arm aged 6 to <12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Cmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 6 to <12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Tmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 6 to <12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    AUC0-last was analyzed independently for participants in the 125 mg dose equivalent arm aged 2 to <6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Cmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 2 to <6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Tmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 2 to <6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    AUC0-last was analyzed independently for participants in the 125 mg dose equivalent arm aged birth to <2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Cmax was analyzed independently for participants in the 125 mg dose equivalent arm aged birth to <2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Tmax was analyzed independently for participants in the 125 mg dose equivalent arm aged birth to <2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • AUC0-last Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    AUC0-last was analyzed independently for participants in the 40 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Cmax Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Cmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Tmax Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Tmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    AUC0-last was analyzed independently for participants in the 40 mg dose equivalent arm aged 6 to <12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Cmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 6 to <12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Tmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 6 to <12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    AUC0-last was analyzed independently for participants in the 40 mg dose equivalent arm aged 2 to <6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Cmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 2 to <6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Tmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 2 to <6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    AUC0-last was analyzed independently for participants in the 40 mg dose equivalent arm aged birth to <2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Cmax was analyzed independently for participants in the 40 mg dose equivalent arm aged birth to <2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Tmax was analyzed independently for participants in the 40 mg dose equivalent arm aged birth to <2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • AUC0-last Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    AUC0-last was analyzed independently for participants in the 10 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Cmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Tmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    AUC0-last was analyzed independently for participants in the 10 mg dose equivalent arm aged 6 to <12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Cmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 6 to <12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Tmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 6 to <12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    AUC0-last was analyzed independently for participants in the 10 mg dose equivalent arm aged 2 to <6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Cmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 2 to <6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Tmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 2 to <6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    AUC0-last was analyzed independently for participants in the 10 mg dose equivalent arm aged from birth to <2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Cmax was analyzed independently for participants in the 10 mg dose equivalent arm aged from birth to <2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Tmax was analyzed independently for participants in the 10 mg dose equivalent arm aged from birth to <2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.

  • Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC0-inf) Following Administration of Single Dose [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Plasma for aprepitant AUC0-inf assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. AUC0-inf data were to be log transformed and analyzed via a linear mixed-effects model containing fixed effects for age for each dose level tested.

  • Apparent Total Clearance (CL/F) of Aprepitant From Plasma Following Administration of Single Dose [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Plasma for aprepitant CL/F assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. CL/F data were to be log transformed and analyzed via a linear mixed-effects model containing fixed effects for age for each dose level tested.

  • Apparent Terminal Half-life (t ½) of Aprepitant Following Administration of Single Dose [ Time Frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration ]
    Plasma for aprepitant t ½ assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. t ½ data were to be log transformed and analyzed via a linear mixed-effects model containing fixed effects for age for each dose level tested.

  • Percentage of Participants Experiencing at Least One Adverse Event (AE) [ Time Frame: From pre-operative phase up to Follow-up (Day 1 to Day 15) ]
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, was also an AE. Changes resulting from normal growth and development which did not vary significantly in frequency or severity from expected levels were not to be considered adverse events. Vomiting and retching were not defined as AEs during the period of data collection (24 hours following the end of surgery) unless they met the definition of an SAE. The percentage of participants experiencing ≥1 AE was reported by dose group.

  • Percentage of Participants Discontinuing Study Due to an AE [ Time Frame: From pre-operative phase up to Follow-up (Day 1 to Day 15) ]
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, was also an AE. Changes resulting from normal growth and development which did not vary significantly in frequency or severity from expected levels were not to be considered adverse events. Vomiting and retching were not defined as AEs during the period of data collection (24 hours following the end of surgery) unless they met the definition of an SAE. The percentage of participants discontinuing study due to an AE was reported by dose group.


Enrollment: 229
Actual Study Start Date: February 12, 2013
Study Completion Date: September 26, 2016
Primary Completion Date: September 26, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aprepitant Dose 1: Equivalent to 125 mg in Adults
Pediatric participants receive a single dose of apprepitant that is equivalent to 125 mg in adults on Day 1 between 1 and 3 hours prior to expected induction of anesthesia, plus placebo for odansetron administered intravenously (IV) immediately prior to anesthesia.
Drug: Aprepitant
Administered as a single oral dose on Day 1 between 1 and 3 hours prior to expected induction of anesthesia. Aprepitant was supplied in a sachet containing a powder for suspension (PFS) that was reconstituted up to total volume of 5 mL using potable water.
Other Names:
  • MK-0869
  • EMEND™
Drug: Placebo to match ondansetron
Participants in the aprepitant regimen received normal saline IV (provided by the site) as the placebo for ondansetron on Day 1, immediately prior to induction of anesthesia.
Experimental: Aprepitant Dose 2: Equivalent to 40 mg in Adults
Pediatric participants receive a single dose of apprepitant that is equivalent to 40 mg in adults on Day 1 between 1 and 3 hours prior to expected induction of anesthesia, plus placebo for odansetron administered IV immediately prior to anesthesia.
Drug: Aprepitant
Administered as a single oral dose on Day 1 between 1 and 3 hours prior to expected induction of anesthesia. Aprepitant was supplied in a sachet containing a powder for suspension (PFS) that was reconstituted up to total volume of 5 mL using potable water.
Other Names:
  • MK-0869
  • EMEND™
Drug: Placebo to match ondansetron
Participants in the aprepitant regimen received normal saline IV (provided by the site) as the placebo for ondansetron on Day 1, immediately prior to induction of anesthesia.
Experimental: Aprepitant Dose 3: Equivalent to 10 mg in Adults
Pediatric participants receive a single dose of apprepitant that is equivalent to 10 mg in adults Day 1 between 1 and 3 hours prior to expected induction of anesthesia, plus placebo for odansetron administered IV immediately prior to anesthesia.
Drug: Aprepitant
Administered as a single oral dose on Day 1 between 1 and 3 hours prior to expected induction of anesthesia. Aprepitant was supplied in a sachet containing a powder for suspension (PFS) that was reconstituted up to total volume of 5 mL using potable water.
Other Names:
  • MK-0869
  • EMEND™
Drug: Placebo to match ondansetron
Participants in the aprepitant regimen received normal saline IV (provided by the site) as the placebo for ondansetron on Day 1, immediately prior to induction of anesthesia.
Active Comparator: Ondansetron
Pediatric participants in the control regimen are administered ondansetron IV on Day 1 immediately prior to induction of anesthesia plus a matching placebo dose to aprepitant as a single oral dose on Day 1 between 1 and 3 hours prior to expected induction of anesthesia.
Drug: Placebo to Aprepitant
Other Name: Matching placebo to aprepritant was administered as a single oral dose on Day 1 between 1 and 3 hours prior to expected induction of anesthesia.
Drug: Ondansetron
Administered IV at a dose of 4 mg for participants >40 kg in weight and 0.1 mg/kg for participants ≤40 kg in weight. In participants <1 month of age, the dose of ondansetron was administered per the product label or based on local standard of care. Ondansetron was supplied by the Sponsor as vials or ampules, depending on the country.
Other Name: Zofran

  Eligibility

Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant enrolled at birth should be at least 37 weeks gestation and ≥3 kg of weight
  • Scheduled to receive general anesthesia AND must have at least one of the following risk factors for post-operative nausea and vomiting (PONV) in addition to receiving general anesthesia:

    1. scheduled to have a surgery with an associated risk of PONV: tonsillectomy, adenoidectomy, strabismus surgery, dental surgery, hydrocelectomy, orchidopexy or herniorraphy; OR
    2. scheduled to have an operative procedure associated with PONV: intraoperative opioid use or anticipated opioid administration within the first 24 hours following surgery.

Exclusion Criteria:

  • Emergency surgery for a life-threatening condition
  • Scheduled to receive propofol for maintenance of anesthesia (Note: propofol is permitted for induction of anesthesia).
  • Expected to receive opioid antagonists (e.g., naloxone, naltrexone) or

benzodiazepine antagonists (e.g., flumazenil)

  • Scheduled to undergo cardiac or neurosurgery
  • Vomiting caused by any organic etiology (such as gastric outlet

obstruction or small bowel obstruction)

  • Vomiting within 24 hours prior to surgery
  • Participant had a nasogastric or oral gastric tube intra- or post-operatively for suctioning gastric contents (note: nasogastric or oral gastric tube intra- or post-operatively could only be used for feeding. Participants were to be excluded if a nasogastric or oral gastric tube for suctioning was routinely used for the type of surgery being performed)
  • Active infection (e.g., pneumonia), congestive heart failure, bradyarrythmia, any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy, or a history of any illness which in the opinion of the investigator, might confound the results of the study or pose unwarranted risk to the participant
  • Use of any illicit drugs, including marijuana or has current evidence of alcohol abuse
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01732458

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01732458     History of Changes
Other Study ID Numbers: 0869-219
2011-006006-27 ( EudraCT Number )
Study First Received: November 19, 2012
Results First Received: August 4, 2017
Last Updated: August 4, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

URL: http://

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Nausea
Vomiting
Postoperative Nausea and Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Postoperative Complications
Pathologic Processes
Anesthetics
Ondansetron
Aprepitant
Fosaprepitant
Central Nervous System Depressants
Physiological Effects of Drugs
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Antipruritics
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Psychotropic Drugs
Anti-Anxiety Agents
Neurokinin-1 Receptor Antagonists

ClinicalTrials.gov processed this record on September 21, 2017