Chemotherapy often causes nausea and vomiting (CINV), and this is a major problem for the children being treated for cancer. To prevent this, a combination of two substances in fixed proportion (IV NEPA) was developed. The two substances are: palonosetron, an antagonist of 5 HT3 receptors, and fosnetupitant, an antagonist of NK1 receptors that transforms into netupitant in the body. The medication is administered through intravenous injection (IV- drip).
This study is built from 2 parts:
Part 1: phase 2, open label Part 2: phase 3 double blind
The detailed description, study design, study milestones and eligibility criteria will reflect the Part 1 requirements
Signed written Informed Consent Form (ICF) by parent(s)/legal guardian of the paediatric patient in compliance with the local laws and regulations. In addition, the signed children's Assent Form according to local requirements.
Male or female in- or out-patient from 0 months (newborns) to <18 years on the date of enrolment (Day 1).
Cohort 1: Patient < 6 months weighing at least 4 kg or patient ≥ 6 months weighing at least 6 kg.
Patient with a predicted life expectancy ≥3 months according to Investigator's opinion.
The patient and/or parent(s)/legal guardian are expected by the Investigator to be non compliant with the study procedures.
Patient has received or is scheduled to receive total body irradiation; total nodal irradiation; upper abdomen radiotherapy; half or upper body irradiation; or radiotherapy of the cranium, craniospinal regions, head and neck, lower thorax region, or the pelvis within 1 week prior to study entry (Day 1) or within 120 h after start of chemotherapy on Day 1 (Cohort 1 patients) or within 168 h (for Cohort 2 patients receiving the last IV NEPA on Day 3) or 216 h (for Cohort 2 patients receiving the last IV NEPA on Day 5) from start of chemotherapy on Day 1.
Known history of allergy to any component of the study treatments or other contraindications to any NK1-RAs or 5-HT3-RAs.
Active infection.
Parallel
IV NEPA (fosnetupitant/palonosetron)
DrugIn NEPA-22-01, different body weight-based dosages of IV NEPA will be applied to patients below and over 3 months of age: Formulation A (for patients ≥3 months of age; 235 mg fosnetupitant/1.5 mg palonosetron per vial) or Formulation B (for patients \<3 months of age; 235 mg fosnetupitant/2.5 mg palonosetron per vial).
Reference Treatment: IV ondansetron infusion
DrugIV Ondansetron Dosing Regimen * Day 1 (before start of chemotherapy): One 30-min infusion of 0.15 mg/kg (ondansetron maximum dose: 8 mg per administration) * Day 1 at 4 h and 8 h after the end of first administration: Two 30-min infusions of 0.15 mg/kg (ondansetron maximum dose: 8 mg per administration)
Reference Treatment: IV fosaprepitant infusion
DrugFosaprepitant IV Dosing Regimen * Patients aged 12 years to \<18 years: a single dose of IV fosaprepitant 150 mg * Patients aged 2 years to \<12 years: a single dose of IV fosaprepitant 4 mg/kg (maximum dose: 150 mg) * Patients aged 6 months to \<2 years: a single dose of IV fosaprepitant 5 mg/kg (maximum dose: 150 mg)
COHORT 1 Neptupitant exposure parameter
Maximum concentration (Cmax)
COHORT 1 Neptupitant exposure
Area under the plasma concentration-time curve
COHORT 2 monitoring of AEs (safety and tolerability of IV NEPA)
monitoring of AEs following repeated IV NEPA administration
COHORT 1: To assess the PK profile of netupitant.
Cmax of netupitant
COHORT 1: To assess the PK profile of fosnetupitant.
Cmax of fosnetupitant
COHORT 1: To assess the PK profile palonosetron.
Cmax of palonosetron
COHORT 1: To assess the PK profile of netupitant
AUC0-48 of netupitant
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