A Study of Aprepitant (MK-0869) in Pediatric Participants Undergoing Surgery (MK-0869-148)

Study Overview
=================
Brief Summary
-----------------
This two part study will determine the appropriate dosing regimen of aprepitant for the prevention of postoperative nausea and vomiting (PONV) in pediatric participants 6 months to 17 years of age, by assessing pharmacokinetic parameters and monitoring safety and tolerability of administered doses. Part I will be an open label investigation of a single dose of aprepitant measuring pharmacokinetics at specified time points up to 48 hours after aprepitant dosing. Part II will be a double blind trial of participants randomized to receive either aprepitant or ondansetron.

Official Title
-----------------
A Multi-center, 2-Part Study to Evaluate the Pharmacokinetics Safety and Tolerability of Aprepitant in Pediatric Patients Undergoing Surgery

Conditions
-----------------
Postoperative Nausea and Vomiting

Intervention / Treatment
-----------------
* Drug: Aprepitant
* Drug: Ondansetron


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant is scheduled to have surgery requiring a 48 hour (Part I) or 24 hour (Part II) hospital stay Participant is scheduled to receive general anesthesia Participant is scheduled to receive opioids (e.g. morphine or fentanyl) Female participants of childbearing potential must have negative pregnancy test prior to drug administration A female participant who is of reproductive potential must agree to remain abstinent or use a barrier form of contraception for at least 14 days prior to, throughout, and for at least one month following the last dose of study medication Participant weighs 6 kg or more Exclusion Criteria: Participant is undergoing surgery for a life-threatening condition Participant is pregnant or breast feeding Participant has vomited within 24 hours prior to surgery Participant has a known history of QT prolongation or is currently taking other medicinal products that lead to QT prolongation Participant has an active infection (e.g., pneumonia), congestive heart failure, bradyarrythmia, any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction), evidence of any clinically significant respiratory, metabolic, hepatic, renal dysfunction, or a history of any illness, including morbid obesity, that might pose unwarranted risk

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Oral Aprepitant<br>In Study Part 1, participants aged 6 months to 17 years received a single oral dose of aprepitant on Day 1. | Drug: Aprepitant<br>* Aprepitant administered orally or intraveously.<br>* Other names: Emend;|
| Experimental: Part 2: Oral Aprepitant<br>In Study Part 2, participants aged 6 months to 17 years received a single oral dose of aprepitant on Day 1. | Drug: Aprepitant<br>* Aprepitant administered orally or intraveously.<br>* Other names: Emend;|
| Active Comparator: Part 2: Intravenous Ondansetron<br>In Study Part 2, participants aged 6 months to 17 years received a single intravenous dose of ondansetron on Day 1. | Drug: Ondansetron<br>* Ondansetron administered intravenously.<br>* Other names: Zofran;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From 0-48 (AUC0-48) of Aprepitant Following a Single Oral Dose in Study Part 1 | Blood samples of 0.5 mL were collected from participants for the analysis of AUC0-48 at specified time points: pre-dose, and 1, 2, 3, 4, 8, 12, 24, and 48 hours post aprepitant single dose. | Pre-dose, and 1, 2, 3, 4, 8, 12, 24, and 48 hours post-dose | 
| Maximum Plasma Concentration (Cmax) of Aprepitant Following a Single Oral Dose in Study Part 1 | Blood samples were collected from participants for the analysis of Cmax up to 48 hours after dosing. | 48 Hours Post-Dose | 
| Time to Maximum Plasma Concentration (Tmax) of Aprepitant Following a Single Oral Dose in Study Part 1 | Blood samples were collected from participants for the analysis of Tmax up to 48 hours after dosing. | 48 Hours Post-Dose | 
| Plasma Concentration of Aprepitant at 24 Hours (C24 hr) Following a Single Oral Dose in Study Part 1 | Blood samples were collected from participants for the analysis of C24 hr at 24 hours after dosing. N/A indicates that >50% of measurements were below the lower level of quantitaion (LLOQ). | 24 Hours Post-Dose | 
| Plasma Concentration of Aprepitant at 48 Hours (C48 hr) Following a Single Oral Dose in Study Part 1 | The mean plasma concentration of aprepitant was evaluated in participants at 48 hours following a single oral dose. | 48 Hours Post-Dose | 
| Number of Participants Experiencing Adverse Events (AEs) |  | Up to 21 Days Post-Surgery | 
| Number of Participants Discontinuing Study Treatment Due to AEs |  | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With No Vomiting Up to 24 Hours Following Surgery in Study Part 2 |  | Up to 24 Hours | 
| Number of Participants With Complete Response Up to 24 Hours Following Surgery in Study Part 2 | Complete response was defined as no vomiting and no use of rescue medication in 0-24 hours post-surgery. | Up to 24 Hours | 
| Number of Participants With No Vomiting Up to 48 Hours Following Surgery Ini Study Part 2 |  | Up to 48 Hours | 
| Number of Participants With Complete Response Up to 48 Hours Following Surgery in Study Part 2 | Complete response was defined as no vomiting and no use of rescue medication in 0-48 hours post-surgery. | Up to 48 Hours | 
| Number of Participants With Vomiting Frequency in Study Part 2 |  | Up to 24 Hours |