fosnetupitant (prodrug of netupitant) and palonosetron hydrochloride for Chemotherapy-induced nausea and vomiting

Inclusion criteria

• {"criterion_text":"- Part I: Cohort 1: Patient < 6 months weighing at least 4 kg or patient ≥ 6 months weighing at least 6 kg. Cohort 2: Patient weighing at least 4 kg.\n- Part I and Part II: Patient with non-clinically significant abnormal laboratory values or with clinically relevant abnormal laboratory values may be enrolled if in the Investigator’s opinion the patient’s safety is not expected to be jeopardized.\n- Part I: Cohort 1: Patient scheduled and eligible to receive at least 1 cycle of single-day HEC. Cohort 2: Patient scheduled and eligible to receive at least 1 cycle of multi-day HEC.\n- Part II: Patient weight at least 6 kg.\n- Part II: Patient scheduled and eligible to receive repeated cycles of multi-day HEC.\n- Part I and Part II: Patient with a predicted life expectancy ≥3 months according to Investigator’s opinion.\n- Part I and Part II: For patients aged ≥10 years: Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2.\n- Part I and Part II: For patient with known hepatic impairment: the patient may be enrolled provided the serum ALT and AST are ≤2.5 ULN, the total bilirubin is ≤1.5 ULN, and in the Investigator’s opinion the impairment is not expected to jeopardize the patient’s safety during the study.\n- Part I and Part II: For patient with known renal impairment: the patient may be enrolled provided the estimated glomerular filtration rate (eGFR) is ≥70 mL/min/1.73m2 (≥50 mL/min/1.73m2 for children <3 months old) (the eGFR should be calculated using the modified Schwartz equation) and in the Investigator’s opinion the impairment is not expected to jeopardize the patient’s safety during the study.\n- Part I and Part II: For patient with known history or predisposition to cardiac abnormalities: as per the Investigator’s opinion, the history/predisposition should not jeopardize patient’s safety during the study."}

Exclusion criteria

• {"criterion_text":"- Part I and Part II: 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 last study drug administration.\n- Part I and Part II: Any illness or condition that, in the opinion of the Investigator, may pose unwarranted risks in administering the investigational product to the patient.\n- Part I and Part II: Uncontrolled medical condition (e.g., uncontrolled insulin-dependent diabetes mellitus).\n- Part I and Part II: Patient experiencing ongoing vomiting from any organic aetiology (including patients with history of gastric outlet obstruction or intestinal obstruction due to adhesions or volvulus), or patient with hydrocephalus.\n- Part I and Part II: Use of any drugs or substances known to interfere with CYP3A4 or CYP2D6 enzymes within 1 week prior to Day 1\n- Part I and Part II: Marked baseline prolongation of QTc interval (QTcF>460 millisecond [msec]). At the discretion of the investigator, criterion may be based on automatic interpretation of results.\n- Part II: Patient planned to receive multi-day HEC with cycle duration of less than 20 days (less than 20 days between 2 consecutive cycles’ Days 1)."}

Primary endpoints

• {"endpoint_text":"- Part I: Cohort 1: Netupitant exposure parameters maximum concentration (Cmax) and area under the plasma concentration-time curve from time zero to the last measurable timepoint (AUClast) and to infinity (AUCinf).","definition_or_measurement_approach":"Pharmacokinetic (PK) measurement of netupitant blood levels to derive Cmax, AUClast and AUCinf from plasma concentration-time data following IV NEPA single-dose administration."}
• {"endpoint_text":"- Part I: Cohort 2: Safety parameters (monitoring of AEs, physical examination, vital signs, clinical laboratory tests [haematology, serum chemistry and urinalysis], and 12-lead ECG) following repeated IV NEPA administration (Days 1, 3 and Days 1, 3, 5) to paediatric cancer patients receiving multi-day HEC treatment.","definition_or_measurement_approach":"Safety assessment via adverse event monitoring, periodic physical examinations, vital signs, laboratory tests (haematology, serum chemistry, urinalysis) and 12-lead ECGs following repeated dosing schedule."}
• {"endpoint_text":"- Part II: Proportion of patients with CR (i.e., no emetic episodes and no rescue medication) during the delayed (>24-120 h) phase of emesis after start of chemotherapy administration in Cycle 1.","definition_or_measurement_approach":"Efficacy measured as the proportion of patients achieving Complete Response (CR: no emetic episodes and no rescue medication) in the delayed phase (>24-120 hours) after chemotherapy start in Cycle 1."}

Secondary endpoints

• {"endpoint_text":"- Part I: Cohort 1: Physical examination, vital signs, clinical laboratory tests (haematology, serum chemistry and urinalysis), 12-lead ECG, and AEs.","definition_or_measurement_approach":"Standard safety assessments (physical exam, vitals, labs, ECG, adverse events) recorded per protocol."}
• {"endpoint_text":"- Part I: Cohort I: - Other PK parameters for netupitant: tmax, (λz, t1/2, AUC0-48), AUC0-120 SD, CL/F, and Vz/F. PK parameters for netupitant metabolites M1, M2, and M3: Cmax, tmax, AUClast, AUC0-48, AUC0-120 SD, AUCinf, λz, t1/2, CL/F, and Vz/F. - PK parameters for fosnetupitant and palonosetron: Cmax, tmax, AUClast, AUC0-48, AUCinf, λz, t1/2, CL, and Vz.","definition_or_measurement_approach":"Detailed PK profiling for netupitant, its metabolites, fosnetupitant and palonosetron using plasma concentration-time sampling to derive standard PK parameters (Cmax, tmax, AUCs, half-life, clearance, volume)."}
• {"endpoint_text":"- Part I: Cohort 1 and Cohort 2: Population PK analysis using samples of patients from both Cohorts and all Age Groups to characterise PK values for fosnetupitant, netupitant, netupitant metabolites M1, M2, and M3, and palonosetron in paediatric patients upon single and multiple IV NEPA administration.","definition_or_measurement_approach":"Population PK modelling using pooled plasma concentration-time data from cohorts and age groups to characterise PK and accumulation."}
• {"endpoint_text":"- Part I: Cohort 1 and Cohort 2: PK/PD correlations between netupitant and palonosetron exposure parameters and antiemetic efficacy parameters (CR).","definition_or_measurement_approach":"Correlation analyses between exposure metrics (e.g., AUC, Cmax) and efficacy outcomes such as CR (no emesis, no rescue medication)."}
• {"endpoint_text":"- Part I: Cohort 1 and Cohort 2: Efficacy parameters, such as Proportion of patients with CR, Proportion of patients with no emetic episodes, Proportion of patients with no rescue medication, and Time to treatment failure","definition_or_measurement_approach":"Efficacy endpoints assessed by patient diaries and clinical records to calculate proportions (CR, no emesis, no rescue medication) and time-to-event measures."}
• {"endpoint_text":"- Part II: in Cycle 1 and repeated Cycles: Efficacy parameters, such as Proportion of patients with CR during the acute delayed and overall phase of emesis, Proportion of patients with no emetic episodes, Proportion of patients with no vomiting, Proportion of patients with no rescue medication, Proportion of patients with no nausea and no use of rescue medication, and Time to treatment failure","definition_or_measurement_approach":"Efficacy measured across time windows (acute 0-24 h, delayed >24-120 h, overall 0-120 h, and extended windows to 168 h/216 h) by recording emetic episodes, nausea scores and rescue medication use."}
• {"endpoint_text":"- Part II: in Cycle 1 and repeated Cycles: Population PK for fosnetupitant, netupitant, netupitant metabolites, and palonosetron will be evaluated using pooled plasma concentration-time data from Study Part I and Part II.","definition_or_measurement_approach":"Population PK evaluation using pooled data from Parts I and II to characterise PK and accumulation across cycles."}
• {"endpoint_text":"- Part II: in Cycle 1 and repeated Cycles: Physical examination, vital signs, clinical laboratory tests (haematology, serum chemistry and urinalysis), 12-lead ECG, and AEs.","definition_or_measurement_approach":"Routine safety monitoring (physical exams, vitals, labs, ECGs, AE reporting) per protocol in Cycle 1 and subsequent cycles."}

Greece

Earliest CTIS Part Ii Submission Date

20-03-2025

Latest Decision Or Authorization Date

19-03-2026

Processing Time Days

364

Number Of Sites

2

Number Of Participants

20

Romania

Earliest CTIS Part Ii Submission Date

21-03-2025

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

399

Number Of Sites

3

Number Of Participants

20

Poland

Earliest CTIS Part Ii Submission Date

24-03-2025

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

364

Number Of Sites

9

Number Of Participants

40

Primary sponsor

Full Name

Helsinn Healthcare S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Ardena Bioanalysis B.V.

Responsibilities

Bioanalysis/PK sample handling (sponsorDuties code: 4); contact Gunnar.flik@ardena.com

Name

Euromed Pharma Services S.r.l.

Responsibilities

Support services (sponsorDuties code: 14); contact moreinfo@euromed.it

Name

Accelsiors AG

Responsibilities

Multiple regulatory and operational roles (sponsorDuties codes: 1,2,3,5,6,8,9,10,11,12,13,14); contact regulatory@accelsiors.com

Name

Accelsiors Greece Monoprosopi I.K.E.

Responsibilities

Local support duties (sponsorDuties code: 12); contact y.litos@accelsiors.com

Name

GBA Central Lab Services GmbH

Responsibilities

Central lab logistics and PK sample shipment coordination (detailed value provided in dossier); contact baerbel.wilke@gba-group.com

Name

Suvoda LLC

Responsibilities

Patient reimbursement services (detailed value provided in dossier); contact clientdeliveryrequests@greenphire.com

Third parties

• {"country":"Netherlands","full_name":"Ardena Bioanalysis B.V.","duties_or_roles":"sponsorDuties codes: [\"4\"] (contact email: Gunnar.flik@ardena.com)","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Euromed Pharma Services S.r.l.","duties_or_roles":"sponsorDuties codes: [\"14\"] (contact email: moreinfo@euromed.it)","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Accelsiors AG","duties_or_roles":"sponsorDuties codes: [\"1\",\"10\",\"11\",\"12\",\"13\",\"14\",\"2\",\"3\",\"5\",\"6\",\"8\",\"9\"] (contact email: regulatory@accelsiors.com)","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Accelsiors Greece Monoprosopi I.K.E.","duties_or_roles":"sponsorDuties codes: [\"12\"] (contact email: y.litos@accelsiors.com)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"GBA Central Lab Services GmbH","duties_or_roles":"Other - Providing supplies for PK sample collection and organizing of the frozen sample shipments to central laboratory for PK analysis (Ardena) (contact email: baerbel.wilke@gba-group.com)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"Other - Patients' reimbursment Services (contact email: clientdeliveryrequests@greenphire.com)","organisation_type":"Non-Pharmaceutical company"}