Phase 2 N=228 Randomized Double-blind Treatment

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

Post-operative Nausea · Post-operative Vomiting

Bottom Line

View on ClinicalTrials.gov: NCT01732458 ↗

Enrolled (actual)

228

Serious AEs

4.1%

Results posted

Sep 2017

Primary outcome: 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 — 7120 hr*ng/mL

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Aprepitant (Drug); Placebo to Aprepitant (Drug); Ondansetron (Drug); Placebo to match ondansetron (Drug)
Age: Pediatric
Sex: All
Sponsor: Merck Sharp & Dohme LLC
Primary completion: Sep 2016

Outcome Measures

Outcome	Result	p-value
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	7120	—
PRIMARY Maximum Concentration (Cmax) of Aprepitant Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group	1340	—
PRIMARY Time to Maximum Concentration (Tmax) of Aprepitant Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group	4.86	—
PRIMARY AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group	10300	—
PRIMARY Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group	1870	—
PRIMARY Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group	6.82	—
PRIMARY AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group	12000	—
PRIMARY Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group	2260	—
PRIMARY Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group	4.91	—
PRIMARY AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group	6410	—
PRIMARY Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group	1280	—
PRIMARY Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group	4.71	—
PRIMARY AUC0-last Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group	2570	—
PRIMARY Cmax Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group	513	—
PRIMARY Tmax Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group	4.17	—
PRIMARY AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group	4730	—
PRIMARY Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group	930	—
PRIMARY Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group	4.22	—
PRIMARY AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group	6320	—
PRIMARY Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group	1290	—
PRIMARY Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group	3.35	—
PRIMARY AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group	7910	—
PRIMARY Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group	1570	—
PRIMARY Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group	4.94	—
PRIMARY AUC0-last Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group	806	—
PRIMARY Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group	131	—
PRIMARY Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group	3.53	—
PRIMARY AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group	1390	—
PRIMARY Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group	289	—
PRIMARY Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group	3.75	—
PRIMARY AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group	1580	—
PRIMARY Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group	300	—
PRIMARY Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group	3.36	—
PRIMARY AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group	1800	—
PRIMARY Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group	336	—
PRIMARY Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group	4.11	—
PRIMARY Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC0-inf) Following Administration of Single Dose	—	—
PRIMARY Apparent Total Clearance (CL/F) of Aprepitant From Plasma Following Administration of Single Dose	—	—
PRIMARY Apparent Terminal Half-life (t ½) of Aprepitant Following Administration of Single Dose	—	—
PRIMARY Percentage of Participants Experiencing at Least One Adverse Event (AE)	31.6; 43.6; 35.7; 48.1	—
PRIMARY Percentage of Participants Discontinuing Study Due to an AE	0; 0; 0; 0	—

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.

Eligibility Criteria

Inclusion Criteria

Participant enrolled at birth should be at least 37 weeks gestation and ≥3 kg of weight
Scheduled to receive general anesthesia AND must have at least one of the following risk factors for post-operative nausea and vomiting (PONV) in addition to receiving general anesthesia:
scheduled to have a surgery with an associated risk of PONV: tonsillectomy, adenoidectomy, strabismus surgery, dental surgery, hydrocelectomy, orchidopexy or herniorraphy; OR
scheduled to have an operative procedure associated with PONV: intraoperative opioid use or anticipated opioid administration within the first 24 hours following surgery.

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01732458). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.