Clinical trial NCT01732458: A Study to Evaluate Aprepitant for the Prevention of Post-Operative Nausea and Vomiting in Children (MK-0869-219)
Official title: A Phase IIb, Partially-Blinded, Randomized, Active Comparator-Controlled Study to Evaluate the Pharmacokinetics/Pharmacodynamics, Safety, and Tolerability of Aprepitant in Pediatric Patients for the Prevention of Post Operative Nausea and Vomiting
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Post-operative Nausea
Post-operative Vomiting
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-11-22
Enrollment: 229
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

  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

Primary outcomes:
measure: 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
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Maximum Concentration (Cmax) of Aprepitant Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Time to Maximum Concentration (Tmax) of Aprepitant Following Administration of 125 mg Dose Equivalent in 12 to 17 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 6 to <12 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in 2 to <6 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: AUC0-last of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Cmax of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Tmax of Aprepitant Following Administration of 125 mg Dose Equivalent in Birth to <2 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: AUC0-last Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Cmax Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Tmax Following Administration of 40 mg Dose Equivalent in 12 to 17 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 6 to <12 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in 2 to <6 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: AUC0-last of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Cmax of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Tmax of Aprepitant Following Administration of 40 mg Dose Equivalent in Birth to <2 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: AUC0-last Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 12 to 17 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 6 to <12 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in 2 to <6 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: AUC0-last of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Cmax of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Tmax of Aprepitant Following Administration of 10 mg Dose Equivalent in Birth to <2 Year Age Group
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC0-inf) Following Administration of Single Dose
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Apparent Total Clearance (CL/F) of Aprepitant From Plasma Following Administration of Single Dose
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Apparent Terminal Half-life (t ½) of Aprepitant Following Administration of Single Dose
timeFrame: 30-60 minutes pre-administration, 2-4 hours post administration, 5-7 hours post administration, 8-10 hours post administration
measure: Percentage of Participants Experiencing at Least One Adverse Event (AE)
timeFrame: From pre-operative phase up to Follow-up (Day 1 to Day 15)
measure: Percentage of Participants Discontinuing Study Due to an AE
timeFrame: From pre-operative phase up to Follow-up (Day 1 to Day 15)
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Salman FT, DiCristina C, Chain A, Afzal AS. Pharmacokinetics and pharmacodynamics of aprepitant for the prevention of postoperative nausea and vomiting in pediatric subjects. J Pediatr Surg. 2019 Jul;54(7):1384-1390. doi: 10.1016/j.jpedsurg.2018.09.006. Epub 2018 Sep 21.