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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Post-operative Vomiting; Post-operative Nausea

Treatments: Drug: Ondansetron; Drug: Aprepitant; Drug: Placebo to Aprepitant; Drug: Placebo to match ondansetron

Study type: Interventional

Funder types: Industry

Identifiers

NCT01732458

2011-006006-27 (EudraCT Number)

0869-219

Details and patient eligibility

About

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.

Full 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.

Enrollment: 229 patients

Sex: All

Ages: Under 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

229 participants in 4 patient groups

Aprepitant Dose 1: Equivalent to 125 mg in Adults

Experimental group

Description:

Pediatric participants receive a single dose of apprepitant that is equivalent to 125 mg in adults on Day 1 between 1 and 3 hours prior to expected induction of anesthesia, plus placebo for odansetron administered intravenously (IV) immediately prior to anesthesia.

Treatment:

Drug: Placebo to match ondansetron

Drug: Aprepitant

Aprepitant Dose 2: Equivalent to 40 mg in Adults

Experimental group

Description:

Pediatric participants receive a single dose of apprepitant that is equivalent to 40 mg in adults on Day 1 between 1 and 3 hours prior to expected induction of anesthesia, plus placebo for odansetron administered IV immediately prior to anesthesia.

Treatment:

Drug: Placebo to match ondansetron

Drug: Aprepitant

Aprepitant Dose 3: Equivalent to 10 mg in Adults

Experimental group

Description:

Pediatric participants receive a single dose of apprepitant that is equivalent to 10 mg in adults Day 1 between 1 and 3 hours prior to expected induction of anesthesia, plus placebo for odansetron administered IV immediately prior to anesthesia.

Treatment:

Drug: Placebo to match ondansetron

Drug: Aprepitant

Ondansetron

Active Comparator group

Description:

Pediatric participants in the control regimen are administered ondansetron IV on Day 1 immediately prior to induction of anesthesia plus a matching placebo dose to aprepitant as a single oral dose on Day 1 between 1 and 3 hours prior to expected induction of anesthesia.

Treatment:

Drug: Placebo to Aprepitant

Drug: Ondansetron