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

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

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.

Study Overview

• Status: Completed
• Conditions: Post-operative Nausea; Post-operative Vomiting
• Intervention / Treatment: Drug: Aprepitant; Drug: Placebo to match ondansetron; Drug: Placebo to Aprepitant; Drug: Ondansetron

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 229
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: Zofran

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2013
• Primary Completion (Actual): September 26, 2016
• Study Completion (Actual): September 26, 2016

Study Registration Dates

• First Submitted: November 19, 2012
• First Submitted That Met QC Criteria: November 19, 2012
• First Posted (Estimate): November 22, 2012

Study Record Updates

• Last Update Posted (Actual): September 25, 2018
• Last Update Submitted That Met QC Criteria: August 27, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Signs and Symptoms, Digestive; Nausea; Vomiting; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Neurokinin-1 Receptor Antagonists; Ondansetron; Aprepitant; Fosaprepitant
• Other Study ID Numbers: 0869-219; 2011-006006-27 (EudraCT Number)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No