Post-operative Nausea, Post-operative Vomiting
Conditions
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.
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.
Interventions
DRUGAprepitant
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.
DRUGOndansetron
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.
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.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This study will be conducted as a partially blinded study. PK samples will not be collected from participants in the control group. To maintain a partial blind, approximately 3 participants randomly selected from each age group in each of the aprepitant treatment groups will not have PK sampling. All participants will remain blinded to the study treatment. The investigator and Sponsor will be blinded to the study medication in participants not providing PK samples. The investigator and Sponsor will remain blinded to the aprepitant dose given to participants from whom PK samples will be collected.
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | AUC0-last was analyzed independently for participants in the 125 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Maximum Concentration (Cmax) of Aprepitant Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Cmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Time to Maximum Concentration (Tmax) of Aprepitant Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Tmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | AUC0-last was analyzed independently for participants in the 125 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Cmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Tmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | AUC0-last was analyzed independently for participants in the 125 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Cmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Tmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | AUC0-last was analyzed independently for participants in the 125 mg dose equivalent arm aged birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Cmax was analyzed independently for participants in the 125 mg dose equivalent arm aged birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Tmax was analyzed independently for participants in the 125 mg dose equivalent arm aged birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| AUC0-last Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | AUC0-last was analyzed independently for participants in the 40 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Cmax Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Cmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Tmax Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Tmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | AUC0-last was analyzed independently for participants in the 40 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Cmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Tmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | AUC0-last was analyzed independently for participants in the 40 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Cmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Tmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | AUC0-last was analyzed independently for participants in the 40 mg dose equivalent arm aged birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Cmax was analyzed independently for participants in the 40 mg dose equivalent arm aged birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Tmax was analyzed independently for participants in the 40 mg dose equivalent arm aged birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| AUC0-last Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | AUC0-last was analyzed independently for participants in the 10 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Cmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Tmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | AUC0-last was analyzed independently for participants in the 10 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Cmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Tmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | AUC0-last was analyzed independently for participants in the 10 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Cmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Tmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | AUC0-last was analyzed independently for participants in the 10 mg dose equivalent arm aged from birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Cmax was analyzed independently for participants in the 10 mg dose equivalent arm aged from birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Tmax was analyzed independently for participants in the 10 mg dose equivalent arm aged from birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. 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. |
| Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC0-inf) Following Administration of Single Dose | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Plasma for aprepitant AUC0-inf assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. 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. |
| Apparent Total Clearance (CL/F) of Aprepitant From Plasma Following Administration of Single Dose | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Plasma for aprepitant CL/F assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. 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. |
| Apparent Terminal Half-life (t ½) of Aprepitant Following Administration of Single Dose | 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration | Plasma for aprepitant t ½ assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. 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. |
| Percentage of Participants Experiencing at Least One Adverse Event (AE) | From pre-operative phase up to Follow-up (Day 1 to Day 15) | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, was also an AE. Changes resulting from normal growth and development which did not vary significantly in frequency or severity from expected levels were not to be considered adverse events. Vomiting and retching were not defined as AEs during the period of data collection (24 hours following the end of surgery) unless they met the definition of an SAE. The percentage of participants experiencing ≥1 AE was reported by dose group. |
| Percentage of Participants Discontinuing Study Due to an AE | From pre-operative phase up to Follow-up (Day 1 to Day 15) | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, was also an AE. Changes resulting from normal growth and development which did not vary significantly in frequency or severity from expected levels were not to be considered adverse events. Vomiting and retching were not defined as AEs during the period of data collection (24 hours following the end of surgery) unless they met the definition of an SAE. The percentage of participants discontinuing study due to an AE was reported by dose group. |
Participant flow
Pre-assignment details
Of 262 screened for inclusion, 229 were randomized to treatment. 1 participant was inadvertently randomized to a 2.5 mg aprepitant dose arm that was not evaluated in this study; therefore the participant was not included in any analyses. Of remaining 228 randomized participants, 8 did not receive treatment.
Participants by arm
| Arm | Count |
|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults Pediatric participants received a single dose of apprepitant that was 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. | 57 |
| Aprepitant Dose 2: Equivalent to 40 mg in Adults Pediatric participants received a single dose of apprepitant that was 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. | 55 |
| Aprepitant Dose 3: Equivalent to 10 mg in Adults Pediatric participants received a single dose of apprepitant that was 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. | 56 |
| Ondansetron Pediatric participants in the control regimen were 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. | 52 |
| Total | 220 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 | 0 | 0 |
| Overall Study | Non-Compliance With Study Drug | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 2 | 2 | 0 |
| Overall Study | Protocol Violation | 2 | 0 | 0 | 2 |
| Overall Study | Screen Failure | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Aprepitant Dose 2: Equivalent to 40 mg in Adults | Aprepitant Dose 3: Equivalent to 10 mg in Adults | Aprepitant Dose 1: Equivalent to 125 mg in Adults | Ondansetron | Total |
|---|---|---|---|---|---|
| Age, Continuous | 87.5 months STANDARD_DEVIATION 64.6 | 85.1 months STANDARD_DEVIATION 59.7 | 90.4 months STANDARD_DEVIATION 64.3 | 86.0 months STANDARD_DEVIATION 65 | 87.3 months STANDARD_DEVIATION 63 |
| Age, Customized 12 years to 17 years | 14 participants | 14 participants | 16 participants | 14 participants | 58 participants |
| Age, Customized 2 years to <6 years | 14 participants | 15 participants | 14 participants | 14 participants | 57 participants |
| Age, Customized 6 years to <12 years | 15 participants | 14 participants | 13 participants | 13 participants | 55 participants |
| Age, Customized Birth to <2 years | 12 participants | 13 participants | 14 participants | 11 participants | 50 participants |
| Sex: Female, Male Female | 19 Participants | 28 Participants | 23 Participants | 16 Participants | 86 Participants |
| Sex: Female, Male Male | 36 Participants | 28 Participants | 34 Participants | 36 Participants | 134 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 57 | 11 / 55 | 12 / 56 | 16 / 52 |
| serious Total, serious adverse events | 0 / 57 | 6 / 55 | 1 / 56 | 2 / 52 |
Outcome results
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Due to the lack of samples beyond 8 hours after dose, the assessment of the terminal elimination phase of the PK profiles was limited and derivation of parameters dependent on lambda (e.g. t ½) was not possible.
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Due to the lack of samples beyond 8 hours after dose, the assessment of the terminal elimination phase of the PK profiles was limited and derivation of parameters dependent on lambda (e.g. CL/F) was not possible.
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Due to the lack of samples beyond 8 hours after dose, the assessment of the terminal elimination phase of the PK profiles was limited and derivation of parameters dependent on lambda (e.g. AUC0-inf) was not possible.
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 12 to 17 years who received a single dose of 125 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | 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 | 7120 hr*ng/mL | Geometric Coefficient of Variation 33 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 12 to 17 years who received a single dose of 10 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | AUC0-last Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group | 806 hr*ng/mL | Geometric Coefficient of Variation 51.9 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 12 to 17 years who received a single dose of 40 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | AUC0-last Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group | 2570 hr*ng/mL | Geometric Coefficient of Variation 41.5 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 2 to \<6 years who received a single dose of 10 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group | 1580 hr*ng/mL | Geometric Coefficient of Variation 45.2 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 6 to \<12 years who received a single dose of 10 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group | 1390 hr*ng/mL | Geometric Coefficient of Variation 77 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged birth to \<2 years who received a single dose of 10 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group | 1800 hr*ng/mL | Geometric Coefficient of Variation 107.8 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 2 to \<6 years who received a single dose of 125 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group | 12000 hr*ng/mL | Geometric Coefficient of Variation 39.7 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 6 to \<12 years who received a single dose of 125 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group | 10300 hr*ng/mL | Geometric Coefficient of Variation 39.5 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged birth to \<2 years who received a single dose of 125 mg aprepitant prior to surgery with available plasma samples were analyzed. Two participants were excluded from the analysis, due to a missing 8-hour post-dose sample and aprepitant concentration in the pre-dose sample, respectively.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group | 6410 hr*ng/mL | Geometric Coefficient of Variation 67.8 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 2 to \<6 years who received a single dose of 40 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group | 6320 hr*ng/mL | Geometric Coefficient of Variation 78.1 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 6 to \<12 years who received a single dose of 40 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group | 4730 hr*ng/mL | Geometric Coefficient of Variation 60.7 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged birth to \<2 years who received a single dose of 40 mg aprepitant prior to surgery with available plasma samples were analyzed. One participant was excluded from the analysis due aprepitant concentration in the pre-dose sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group | 7910 hr*ng/mL | Geometric Coefficient of Variation 153.2 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 12 to 17 years who received a single dose of 40 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Cmax Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group | 513 ng/mL | Geometric Coefficient of Variation 41.6 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 12 to 17 years who received a single dose of 10 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group | 131 ng/mL | Geometric Coefficient of Variation 50.8 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 2 to \<6 years who received a single dose of 10 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group | 300 ng/mL | Geometric Coefficient of Variation 49.9 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 6 to \<12 years who received a single dose of 10 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group | 289 ng/mL | Geometric Coefficient of Variation 128.4 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged birth to \<2 years who received a single dose of 10 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group | 336 ng/mL | Geometric Coefficient of Variation 112 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 2 to \<6 years who received a single dose of 125 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group | 2260 ng/mL | Geometric Coefficient of Variation 35.7 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 6 to \<12 years who received a single dose of 125 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group | 1870 ng/mL | Geometric Coefficient of Variation 53 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged birth to \<2 years who received a single dose of 125 mg aprepitant prior to surgery with available plasma samples were analyzed. One participant was excluded from the analysis due to aprepitant concentration in the pre-dose sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group | 1280 ng/mL | Geometric Coefficient of Variation 78.5 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 2 to \<6 years who received a single dose of 40 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group | 1290 ng/mL | Geometric Coefficient of Variation 81.7 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 6 to \<12 years who received a single dose of 40 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group | 930 ng/mL | Geometric Coefficient of Variation 66.7 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged birth to \<2 years who received a single dose of 40 mg aprepitant prior to surgery with available plasma samples were analyzed. One participant was excluded from the analysis due aprepitant concentration in the pre-dose sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group | 1570 ng/mL | Geometric Coefficient of Variation 146.3 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 12 to 17 years who received a single dose of 125 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Maximum Concentration (Cmax) of Aprepitant Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group | 1340 ng/mL | Geometric Coefficient of Variation 43.9 |
Primary
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.
Time frame: From pre-operative phase up to Follow-up (Day 1 to Day 15)
Population: All randomized participants who received at least one dose of study treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Percentage of Participants Discontinuing Study Due to an AE | 0 percentage of participants |
| Aprepitant Dose 2: Equivalent to 40 mg in Adults | Percentage of Participants Discontinuing Study Due to an AE | 0 percentage of participants |
| Aprepitant Dose 3: Equivalent to 10 mg in Adults | Percentage of Participants Discontinuing Study Due to an AE | 0 percentage of participants |
| Ondansetron | Percentage of Participants Discontinuing Study Due to an AE | 0 percentage of participants |
Primary
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.
Time frame: From pre-operative phase up to Follow-up (Day 1 to Day 15)
Population: All randomized participants who received at least one dose of study treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Percentage of Participants Experiencing at Least One Adverse Event (AE) | 31.6 percentage of participants |
| Aprepitant Dose 2: Equivalent to 40 mg in Adults | Percentage of Participants Experiencing at Least One Adverse Event (AE) | 43.6 percentage of participants |
| Aprepitant Dose 3: Equivalent to 10 mg in Adults | Percentage of Participants Experiencing at Least One Adverse Event (AE) | 35.7 percentage of participants |
| Ondansetron | Percentage of Participants Experiencing at Least One Adverse Event (AE) | 48.1 percentage of participants |
Comparison: The Miettinen and Nurminen method was used to provide 95% confidence intervals (CIs) for between-treatment differences in the percentage of participants with events.95% CI: [-34, 2]
Comparison: The Miettinen and Nurminen method was used to provide 95% confidence intervals (CIs) for between-treatment differences in the percentage of participants with events.95% CI: [-22.9, 14.3]
Comparison: The Miettinen and Nurminen method was used to provide 95% confidence intervals (CIs) for between-treatment differences in the percentage of participants with events.95% CI: [-30.3, 6.3]
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 12 to 17 years who received a single dose of 125 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Time to Maximum Concentration (Tmax) of Aprepitant Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group | 4.86 hour (hr) | Geometric Coefficient of Variation 56.5 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 12 to 17 years who received a single dose of 40 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Tmax Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group | 4.17 hr | Geometric Coefficient of Variation 69.4 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 12 to 17 years who received a single dose of 10 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group | 3.53 hr | Geometric Coefficient of Variation 54.1 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 2 to \<6 years who received a single dose of 10 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group | 3.36 hr | Geometric Coefficient of Variation 45.8 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 6 to \<12 years who received a single dose of 10 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group | 3.75 hr | Geometric Coefficient of Variation 57.9 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged birth to \<2 years who received a single dose of 10 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group | 4.11 hr | Geometric Coefficient of Variation 48.2 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 2 to \<6 years who received a single dose of 125 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group | 4.91 hr | Geometric Coefficient of Variation 51.9 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 6 to \<12 years who received a single dose of 125 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group | 6.82 hr | Geometric Coefficient of Variation 26.8 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged birth to \<2 years who received a single dose of 125 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group | 4.71 hr | Geometric Coefficient of Variation 51.3 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 2 to \<6 years who received a single dose of 40 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group | 3.35 hr | Geometric Coefficient of Variation 43 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged 6 to \<12 years who received a single dose of 40 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group | 4.22 hr | Geometric Coefficient of Variation 53.4 |
Primary
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.
Time frame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
Population: Participants aged birth to \<2 years who received a single dose of 40 mg aprepitant prior to surgery with available plasma samples were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant Dose 1: Equivalent to 125 mg in Adults; 12 to 17 | Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group | 4.94 hr | Geometric Coefficient of Variation 38 |