E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of Postoperative nausea and vomiting in pediatric patients. |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of Postoperative nausea and vomiting in pediatric patients. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
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 | 10042613 - Surgical and medical procedures |
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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 |
To estimate postoperative aprepitant plasma concentration profiles and pharmacokinetic parameters (AUC0-48, Cmax, Tmax, C24 hr, and C48 hr) obtained from infants 6 months to < 2 years of age and children 2 to < 6 years, 6 to < 12 years, and 12 to 17 years of age administered oral aprepitant preoperatively. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of the administered dose(s) of aprepitant in patients 6 months to 17 years of age. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients are 6 months to 17 years of age at the time of study entry
2. Patient is scheduled to undergo surgery (such as but not limited to abdominal, pelvic, perineal, plastic surgery to repair physical deformity, or orthopedic surgery) requiring a 48 hour hospital stay after the end of surgery.
3. Patient weighs ≥ 6 kg and has an American Society of anesthesia (ASA) physical status of I-III.
4. Patient is scheduled to receive postoperative opioids (e.g., morphine, or fentanyl) by oral, rectal, intramuscular (IM) or IV administration, or patient controlled analgesia (PCA).
5. Patient is scheduled to receive general anesthesia with the following general anesthetic regimen:
• Induction with any inhaled anesthetic agent
• Opioids (e.g., fentanyl, morphine, or hydromorphone
6. Patient has an existing vascular catheter (peripheral or central) prior to receiving aprepitant
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E.4 | Principal exclusion criteria |
1. Patient is undergoing surgery for a life threatening condition.
2. Placement of nasogastric or oral gastric tube intra- or postoperatively. (Patients should be excluded if a nasogastric or oral gastric tube is routinely used for the type of surgery to be performed.
3. Patient is scheduled to receive propofol for maintenance of anesthesia. (Note: propofol is permitted for induction of anesthesia in addition to an inhaled anesthetic agent.)
4. Patient is taking, or has taken within 7 days of surgery the following cytochrome:
P450 3A4(CYP3A4) substrates:Terfenadine, Cisapride, Astemizole, Pimozide
5. Patient is taking, or has taken within 7 days of surgery the following CYP3A4 inhibitors:
• Clarithromycin, erythromycin, ketoconazole, itraconazole ,fluconazole or telithromycin
6. Patient is taking, or has taken within 30 days of surgery the following CYP3A4 inducers:
• Phenytoin or carbamazepine, barbiturates, rifampicin or rifabutin, St. John’s Wort
7. Patient is allergic to scheduled preoperative tranquilizer, operative anesthetics,
postoperative analgesia, ondansetron or any 5HT3 antagonist, or aprepitant.
8. Patient is expected to receive neuroaxial anesthesia such as epidural, spinal or caudal anesthesia. (Patients should be excluded if neuroaxial anesthesia is routinely used for the type of surgery to be performed.
9. 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetic Endpoint (Part I)
Pharmacokinetic (PK) profile (AUC0-48, Cmax, Tmax, C24 hr, C48 hr) of the administered dose of aprepitant will be determined for patients aged 6 months to 17 years.
Safety Endpoints:.
Any, drug-related, serious, and serious drug-related adverse experience(s) during study therapy plus 14 days post therapy or drug-related adverse experience(s) leading to discontinuation of aprepitant therapy will be analyzed to assess tolerability.. Safety data will be assessed separately for each Part.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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) | Yes |
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) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 |
Mexico |
Russian Federation |
Turkey |
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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Last Patient Last Visit (LPLV) |
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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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |