Pediatric study to evaluate the appropriate dose for aprepitant in pediatric patients undergoing surgery.
- Conditions
- Post Operative Nausea and Vomiting in surgical patientsMedDRA version: 15.0Level: LLTClassification code 10036901Term: Prophylaxis against postoperative nausea and vomitingSystem Organ Class: 10042613 - Surgical and medical proceduresTherapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]
- Registration Number
- EUCTR2011-006006-27-ES
- Lead Sponsor
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 260
1. Patient is from birth (at least 37 weeks gestation and > or = to 3 kg of weight) to 17 years of age at the time of randomization.
2. Parent/guardian (legally authorized representative) agrees to the patient?s participation as indicated by parent/legal guardian signature on the informed consent form. Patients 12-17 years of age, or as required by local regulation, assents and has the ability to understand the nature and intent of the study including the ability to comply with study procedures, and is willing to keep scheduled study visits. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in the Future Biomedical Research.
3. Patient is scheduled to receive general anesthesia AND:
Patients must have at least one of the following risk factors for PONV (in addition to receiving general anesthesia):
-Patient is scheduled to have a surgery with an associated risk of PONV: tonsillectomy, adenoidectomy, strabismus surgery, dental surgery, hydrocelectomy, orchidopexy or herniorraphy.
?OR
-Patient is scheduled to have an operative procedure associated with PONV: intraoperative opioid use or anticipated opioid administration within the first 24 following surgery.
4. Patient falls within ASA Physical Status Classification I, II or III. (Appendix 6.1).
5. Female patient who has begun menses has a negative urine pregnancy test prior to randomization. Females of reproductive potential agree to remain abstinent or use a barrier form of contraceptive for at least 14 days prior to, throughout, and for at least
1 month following the last dose of study medication. Females taking oral contraceptive agents must agree to add a barrier form of contraception. For countries where abstinence is not considered an accepted method of birth control, a locally acceptable birth control method must be used.
Are the trial subjects under 18? yes
Number of subjects for this age range: 260
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Patient is undergoing emergency surgery for a life threatening condition.
2. Patient is scheduled to receive propofol for maintenance of anesthesia. (Note: propofol is permitted for induction of anesthesia).
3. Patient is expected to receive opioid antagonists (e.g., naloxone, naltrexone) or benzodiazepine antagonists (e.g., flumazenil)
4. Patient is scheduled to undergo cardiac or neurosurgery.
5. Patient has vomited within 24 hours prior to surgery.
6. Patient has an active infection (e.g., pneumonia), any uncontrolled disease (e.g., diabetic ketoacidosis, pre-existing gastrointestinal conditions/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 in administering study drug/comparator to the patient.
7. Patient has a nasogastric or oral gastric tube intra- or post-operatively for suctioning gastric contents (Note: nasogastric or oral gastric tube intra- or post-operatively may ONLY be used for feeding. Patients should be excluded if a nasogastric or oral gastric tube is routinely used for the type of surgery to be performed).
8. Patients with a know history of CT prolongation.
9. Patient is allergic to aprepitant, ondansetron or any 5-HT3 antagonist.
10. Patient is taking the anti-coagulant warfarin.
11. Patient is mentally incapacitated or has a significant emotional or psychiatric disorder that in the opinion of the investigator precludes study entry.
12. Patients with a known history of QT prolongation or is taking any medication that is known to lead to QT prolongation.
13. Patient is currently a user of any illicit drugs, including marijuana or has current evidence of alcohol abuse (defined using DSM-IV criteria) as determined by the investigator.
14. Patient has ever participated in a study with aprepitant or fosaprepitant, is currently participating in a study with another NK-1 antagonist, or has taken a non-approved (investigational) drug within the last 4 weeks.
15. Patient is allergic to aprepitant, ondansetron or any 5-HT3 antagonist.
16. Patient is taking the anti-coagulant warfarin.
17.-20. Other Excluded Medications:
NOTE: The CYP3A4 and antiemetics listed in Table 2-1 of the protocol, is not exhaustive. The SPONSOR should be consulted in individual cases where the patient is taking a CYP3A4 or antiemetics not listed below.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To estimate post-operative aprepitant plasma concentration profiles and pharmacokinetic parameters by population analysis including historical data (e.g. Cmax, Tmax, AUC0-?, t1/2, CL/F) in Dose 1, 2, 3 (Dose 4 if needed) obtained from pediatric patients from birth to 17 years of age administered oral aprepitant preoperatively.<br><br>Safety: <br>To evaluate the safety and tolerability of the administered dose(s) of aprepitant in pediatric patients from birth to 17 years of age.;Secondary Objective: No secondary objective;Primary end point(s): Pharmacokinetic endpoints are Cmax, Tmax, AUC0-?, t1/2 and CL/F estimated by population methods, including the use of historic data in the population modeling, in each age group for all aprepitant treatments.;Timepoint(s) of evaluation of this end point: -30 to 60 minutes prior to aprepitant administration<br>-2 to 4 hours post aprepitant administration<br>-5 to 7 hours post aprepitant administration <br>-8 to 10 hours post aprepitant administration.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): There are no secondary end points for this study.;Timepoint(s) of evaluation of this end point: There are no secondary end points for this study.