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

NCT ID: NCT01732458

Last Updated: 2018-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 229 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-12
• Study Completion Date: 2016-09-26

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.

Conditions

Post-operative Nausea; Post-operative Vomiting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Aprepitant Dose 1: Equivalent to 125 mg in Adults

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.

Group Type: EXPERIMENTAL

Aprepitant

Intervention Type: DRUG

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.

Placebo to match ondansetron

Intervention Type: DRUG

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.

Aprepitant Dose 2: Equivalent to 40 mg in Adults

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.

Group Type: EXPERIMENTAL

Aprepitant

Intervention Type: DRUG

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.

Placebo to match ondansetron

Intervention Type: DRUG

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.

Aprepitant Dose 3: Equivalent to 10 mg in Adults

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.

Group Type: EXPERIMENTAL

Aprepitant

Intervention Type: DRUG

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.

Placebo to match ondansetron

Intervention Type: DRUG

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.

Ondansetron

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.

Group Type: ACTIVE_COMPARATOR

Placebo to Aprepitant

Intervention Type: DRUG

Ondansetron

Intervention Type: DRUG

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.

Interventions

Aprepitant

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.

Intervention Type: DRUG

Placebo to Aprepitant

Intervention Type: DRUG

Ondansetron

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.

Intervention Type: DRUG

Placebo to match ondansetron

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.

Intervention Type: DRUG

Other Intervention Names

MK-0869; EMEND™; Matching placebo to aprepritant was administered as a single oral dose on Day 1 between 1 and 3 hours prior to expected induction of anesthesia.; Zofran

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

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: DERIVED

PMID: 30381138 (View on PubMed)

Other Identifiers

2011-006006-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

0869-219

Identifier Type: -

Identifier Source: org_study_id