E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of chemotherapy induced nausea and vomiting in pediatric subjects |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of chemotherapy induced nausea and vomiting in pediatric subjects |
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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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054133 |
E.1.2 | Term | Prophylaxis of 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 |
Efficacy
To compare the three-day oral aprepitant regimen (aprepitant plus ondansetron), to ondansetron alone (hereafter referred to as the control regimen) with respect to the efficacy endpoint of Complete Response (no vomiting, no retching, and no use of rescue medication) in the 25 to 120 hours following the initiation of emetogenic chemotherapy in Cycle 1 (delayed phase). |
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E.2.2 | Secondary objectives of the trial |
Efficacy
- To compare the three-day oral aprepitant regimen, to the control regimen with respect to the efficacy endpoint of Complete Response in the 0 to 24 hours following the initiation of emetogenic chemotherapy in Cycle 1 (acute phase).
-To compare the three-day oral aprepitant regimen, to the control regimen with respect to the efficacy endpoint of Complete Response in the 0-120 hours following the initiation of emetogenic chemotherapy in Cycle 1 (overall phase).
- To compare the three-day oral aprepitant regimen, to the control regimen with respect to the efficacy endpoint of No Vomiting, regardless of rescue medication use, in the 120 hours following the initiation of emetogenic chemotherapy in Cycle 1 (overall phase).
Safety
To assess the safety and tolerability of the three-day oral aprepitant regimen in patients from 6 months to 17 years of age who are receiving emetogenic chemotherapy in Cycle 1. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Cycle 1:
-Is 6 months to 17 years of age at time of study entry
-Is scheduled to receive chemotherapeutic agent(s) associated with moderate, high risk or very high risk of vomiting for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting
-Is expected to receive ondansetron as part of their antiemetic regimen
-If female and has begun menses, must has a negative urine pregnancy test prior to randomization. A female who is of reproductive potential agrees to remain abstinent or use a barrier form of contraception for at least 14 days prior to, throughout, and for at least one month following the last dose of study medication
-If >10 years old, have a Karnofsky score ≥ 60; if ≤ 10 years have a Lansky Play Performance score ≥ 60
-Have a predicted life expectancy of ≥ 3 months
Optional Cycles 2-6:
-Participant has, in the opinion of the investigator, completed the preceding cycle of chemotherapy and related study procedures satisfactorily |
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E.4 | Principal exclusion criteria |
Cycle 1:
-Has vomited in the 24 hours prior to Treatment Day 1
-Is scheduled to receive stem cell rescue therapy in conjunction with study related course(s) of emetogenic chemotherapy
-Has received or will receive radiation therapy to the abdomen or pelvis within a week prior to Treatment Day 1 or during the course of the study
-Is pregnant or breast feeding
-Is allergic to aprepitant, ondansetron, or any other 5-hydroxytryptamine type-3 receptor (5-HT3) antagonist
-Has a symptomatic primary or metastatic CNS malignancy causing nausea and/or vomiting
-History of QT prolongation or taking other medicinal products that lead to QT prolongation
-Has an active infection (e.g., pneumonia), congestive heart failure, bradyarrhythmia, or any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy, which in the opinion of the investigator, might confound the results of the study or pose unwarranted risk in administering study drug to the participant
-Has had benzodiazepine or opioid therapy initiated within 48 hours of study drug administration, except for single daily doses of triazolam, temazepam, or midazolam
-Has been started on systemic corticosteroid therapy within 72 hours prior to study drug administration or is planned to receive a corticosteroid as part of the chemotherapy regimen
-Is currently taking warfarin
Optional Cycles 2-6:
All exclusion criteria from Cycle 1 apply except for vomiting in the 24 hours prior to Treatment Day 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Participants With a Complete Response in the Delayed Phase of Cycle 1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
25 to 120 hours after start of chemotherapy |
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E.5.2 | Secondary end point(s) |
1. Percentage of Participants With a Complete Response in the Acute Phase of Cycle 1
2. Percentage of Participants With a Complete Response in the Overall Phase of Cycle 1
3. Percentage of Participants With No Vomiting in the Overall Phase of Cycle 1 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. up to 24 hours after start of chemotherapy
2. and 3. up to 120 hours after start of chemotherapy |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.5 | Parallel group | Yes |
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 | No |
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 |
Argentina |
Chile |
Colombia |
Croatia |
Dominican Republic |
Ecuador |
Israel |
Korea, Republic of |
Mexico |
Peru |
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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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 | 11 |