E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post Operative Nausea and Vomiting in surgical patients |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of postoperative nausea and vomiting |
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E.1.1.2 | Therapeutic area | Body processes [G] - Biological Phenomena [G16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036901 |
E.1.2 | Term | Prophylaxis against postoperative nausea and vomiting |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1) Objective of Pharmacokinetics: 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.
2) Objective of Safety: To evaluate the safety and tolerability of the administered dose(s) of aprepitant in pediatric patients from birth to 17 years of age.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on DNA (buccal swabs) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific
understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time.
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E.3 | Principal inclusion criteria |
1. Patient is birth (at least 37 weeks gestation and ≥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.
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E.4 | Principal exclusion criteria |
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 with vomiting of organic etiology (such as gastric outlet obstruction or small bowel obstruction).
6. Patient has vomited within 24 hours prior to surgery.
7. Patient is pregnant or breast-feeding. (Female patients of child bearing potential are required to have a negative urine pregnancy test prior to entering the study on the morning of surgery).
8. Patient has a nasogastric or oral gastric tube intra- or postoperatively for suctioning gastric contents
9. Patient having abnormalities in laboratory tests for liver and kidney function
10. Patient has an 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 in administering study drug or concomitant therapy to the patient.
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 or other drugs, as indicated in a protocol.
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-30 to 60 minutes prior to aprepitant administration
-2 to 4 hours post aprepitant administration
-5 to 7 hours post aprepitant administration
-8 to 10 hours post aprepitant administration. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Brazil |
Canada |
Chile |
Guatemala |
India |
Mexico |
Peru |
Puerto Rico |
Russian Federation |
Turkey |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |