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

NCT01732458 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 0869-2192011-006006-27
• Study Type: interventional
• Target: 229
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Post-operative Nausea; Post-operative Vomiting

Outcome Measures

Primary Outcomes (41)

• 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

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Maximum Concentration (Cmax) of Aprepitant Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Time to Maximum Concentration (Tmax) of Aprepitant Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• AUC0-last Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Cmax Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Tmax Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• AUC0-last Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC0-inf) Following Administration of Single Dose

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Apparent Total Clearance (CL/F) of Aprepitant From Plasma Following Administration of Single Dose

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Apparent Terminal Half-life (t ½) of Aprepitant Following Administration of Single Dose

  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. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. 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.

  30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration

• Percentage of Participants Experiencing at Least One Adverse Event (AE)

  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.

  From pre-operative phase up to Follow-up (Day 1 to Day 15)

• Percentage of Participants Discontinuing Study Due to an AE

  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.

  From pre-operative phase up to Follow-up (Day 1 to Day 15)

Study Arms (4)

Aprepitant Dose 1: Equivalent to 125 mg in Adults

EXPERIMENTAL

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; Drug: Placebo to match ondansetron

Aprepitant Dose 2: Equivalent to 40 mg in Adults

EXPERIMENTAL

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; Drug: Placebo to match ondansetron

Aprepitant Dose 3: Equivalent to 10 mg in Adults

EXPERIMENTAL

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; Drug: Placebo to match ondansetron

Ondansetron

ACTIVE COMPARATOR

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; Drug: Ondansetron

Interventions

Aprepitant DRUG

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.

Also known as: MK-0869, EMEND™

Aprepitant Dose 1: Equivalent to 125 mg in Adults; Aprepitant Dose 2: Equivalent to 40 mg in Adults; Aprepitant Dose 3: Equivalent to 10 mg in Adults

Placebo to Aprepitant DRUG

Also known as: 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.

Ondansetron

Ondansetron DRUG

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.

Also known as: Zofran

Ondansetron

Placebo to match ondansetron DRUG

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.

Aprepitant Dose 1: Equivalent to 125 mg in Adults; Aprepitant Dose 2: Equivalent to 40 mg in Adults; Aprepitant Dose 3: Equivalent to 10 mg in Adults

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Salman FT, DiCristina C, Chain A, Afzal AS. Pharmacokinetics and pharmacodynamics of aprepitant for the prevention of postoperative nausea and vomiting in pediatric subjects. J Pediatr Surg. 2019 Jul;54(7):1384-1390. doi: 10.1016/j.jpedsurg.2018.09.006. Epub 2018 Sep 21.

  PMID: 30381138 DERIVED

MeSH Terms

Interventions

Aprepitant; Ondansetron

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2012
• First Posted: November 22, 2012
• Study Start: February 12, 2013
• Primary Completion: September 26, 2016
• Study Completion: September 26, 2016
• Last Updated: September 25, 2018
• Results First Posted: September 6, 2017

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share