Completed
`PK/ PD Study of Netupitant and Palonosetron in Pediatric Patients for
`Prevention of Chemotherapy-induced Nausea and Vomiting (CINV)
`ClinicalTrials.gov ID NCT03204279
`SponsorHelsinn Healthcare SA
`Information provided by Helsinn Healthcare SA (Responsible Party)
`Last Update Posted 2024-06-25
`Study Details Tab
`Study Overview
`Brief Summary
`This study is Phase 2 pharmacokinetic (PK) and pharmacodynamic (PD) dose-finding study of oral
`netupitant administered concomitantly with oral palonosetron in pediatric cancer patients for the
`prevention of nausea and vomiting associated with emetogenic chemotherapy. Two different netupitant
`dosages will be tested in patients aged from 3 months to < 18 years: 1.33 mg/kg up to a maximum of
`100 mg, and 4 mg/kg up to a maximum of 300 mg. All netupitant doses in all age classes will be
`concomitantly administered with palonosetron 20 μg/kg (up to a maximum dose of 1.5 mg) which is
`the IV palonosetron dose approved by USA FDA for the pediatric population. The primary objective is to
`investigate the PK/PD relationship between netupitant exposure (AUC, Cmax) and antiemetic efficacy
`(CR in delayed phase) after a single oral netupitant administration, concomitantly with oral
`palonosetron in pediatric cancer patients receiving Moderately Emetogenic Chemotherapy (MEC) or
`Highly Emetogenic Chemotherapy (HEC) cycles. Efficacy parameter to be used in the correlation is the
`The U.S. government does not review or approve the safety and science of all studies
`listed on this website.
`Read our full disclaimer(https://clinicaltrials.gov/about-site/disclaimer) for details.
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 1/15
`HELSINN EXHIBIT 2023
`Azurity Pharmaceuticals, Inc. v. Helsinn Healthcare S.A.
`IPR2025-00948
`Page 1 of 15
`
`
`
`
`
`
`
`proportion of patients with Complete Response (CR i.e., no emetic episodes and no rescue medication)
`during (> 24-120 h after the start of chemotherapy on Day 1).
`The secondary objectives are to assess the safety and tolerability after single oral administration of
`netupitant given concomitantly with a single oral administration of palonosetron; to evaluate the
`pharmacokinetic (AUC, Cmax, tmax and t1/2) of oral palonosetron at the fixed dose of 20 μg/kg in
`pediatric patients with the concomitant administration of netupitant. A total of 92 pediatric cancer
`patients receiving either HEC or MEC will be enrolled in the study.
`Official Title
`A Multicenter Multinational Randomized Double Blind PK/PD Dose-finding Study of Oral Netupitant
`Given With Oral Palonosetron in Pediatric Cancer Patients for Prevention of Nausea and Vomiting
`Associated With Emetogenic Chemotherapy
`Conditions
`Chemotherapy-induced Nausea and Vomiting (CINV)
`Intervention / Treatment
`Drug: Netupitant
`Drug: Palonosetron
`Drug: Netupitant
`Drug: Palonosetron
`Other Study ID Numbers
`Study Start (Actual)
`2017-08-31
`Primar
`y Completion (Actual)
`2019-09-30
`Study Completion (Actual)
`2019-09-30
`Enrollment (Actual)
`67
`Study Typ
`e
`Inter
`ventional
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 2/15
`Page 2 of 15
`
`
`
`
`
`
`
`Phase
`Phase 2
`Resource links provided by the National Library of Medicine
`MedlinePlus(https://medlineplus.gov/) related topics:  Nausea and
`Vomiting(https://medlineplus.gov/nauseaandvomiting.html)
`Drug Information(https://dailymed.nlm.nih.gov/dailymed/) available for: 
`Palonosetron(https://dailymed.nlm.nih.gov/dailymed/search.cfm?
`labeltype=human&query=Palonosetron)
`FDA Drug and Device Resources(https://clinicaltrials.gov/fda-links)
`Contacts and Locations
`This section provides contact details for people who can answer questions about joining this study, and
`information on where this study is taking place.
`To learn more, please see the Contacts and Locations section in How to Read a Study
`Record(https://clinicaltrials.gov/study-basics/how-to-read-study-record#contacts-and-locations).
`This study has 17 locations
`United States
`Delaware Locations
`Wilmington, Delaware, United States, 19803
`Nemours/A.I. duPont Hospital for Children
`Florida Locations
`Jacksonville, Florida, United States, 32207
`Nemours Children's Clinic
`Orlando, Florida, United States, 32827
`Nemours Children's Hospital - Orlando
`Maine Locations
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 3/15
`Page 3 of 15
`
`
`
`
`
`
`
`Scarborough, Maine, United States, 04074
`Maine Medical Center - Cancer Medicine and
`Blood Disorders - Scarborough
`South Carolina Locations
`Charleston, South Carolina, United States,
`29425
`Medical University of South Carolina
`Russian Federation
`Chelyabinsk, Russian Federation
`Chelyabinsk Regional Children's Clinical Hospital
`Krasnodar, Russian Federation
`Children's Territorial Clinical Hospital
`Moscow, Russian Federation
`Dmitry Rogachev National Scientific and
`Practical Center for Pediatric Hematology,
`Oncology and Immunology
`St. Petersburg, Russian Federation
`City Clinical Hospital #31
`St. Petersburg, Russian Federation
`First I.P. Pavlov State Medical University of St.
`Petersburg
`Voronezh, Russian Federation, 394024
`Voronezh Regional Children's Cinical Hospital
`#1
`Yekaterinburg, Russian Federation
`Regional Children's Clinical Hospital #1
`Serbia
`Belgrade, Serbia
`University Children's Hospital, Center for
`Pediatrics, Department of Hematology and
`Oncology
`Nis, Serbia
`Clinical Center Nis, Clinic of Pediatric Internal
`Diseases
`Ukraine
`Dnipro, Ukraine, 49100
`Dnipropetrovsk Regional Children's Clinical
`Hospital
`Kyiv, Ukraine
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 4/15
`Page 4 of 15
`
`
`
`
`
`
`
`National Institute of Cancer, Research
`Department of Pediatric Oncology
`Lviv, Ukraine
`West Ukrainian Specialized Children's Medical
`Center, Department of Pediatric Surgery
`Participation Criteria
`Researchers look for people who fit a certain description, called eligibility criteria. Some examples of
`these criteria are a person's general health condition or prior treatments.
`For general information about clinical research, read Learn About
`Studies(https://clinicaltrials.gov/study-basics/learn-about-studies).
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 5/15
`Page 5 of 15
`
`
`
`
`
`
`
`Eligibility Criteria
`Description
`Inclusion Criteria:
`1. Signed written informed consent by parent(s)/legal guardians of the pediatric patient in
`compliance with the local laws and regulations. In addition signed children's assent form
`according to local requirements.
`2. Male or female in- or out-patient from birth to < 18 years at the time of randomization.
`3. Patient weight at least 3.3 kg.
`4. Naïve or non-naïve patient with histologically, and/or cytologically (or imaging in the case of
`brain tumors) confirmed malignant disease.
`5. Scheduled and eligible to receive at least one moderately or highly emetogenic
`chemotherapeutic agent on Day 1 only or for multiple days.
`6. For patient aged ≥ 10 years: Eastern Cooperative Oncology Group Performance Status
`(ECOG PS) ≤ 2.
`7. For patient aged 2 years with known mild to moderate hepatic impairment: in the
`Investigator's opinion the impairment does not jeopardize patient's safety during the study.
`8. For patient aged 2 years with known mild to moderate renal impairment: in the
`Investigator's opinion the impairment should not jeopardize patient's safety during the
`study.
`9. For patient with known history or predisposition to cardiac abnormalities: in the
`Investigator's opinion the history/predisposition should not jeopardize patient's safety
`during the study.
`10. If the patient is female, she shall: a) not have attained menarche yet or b) have attained
`menarche and have a negative pregnancy test at the screening visit and at Day 1.
`11. Male or female fertile patient using reliable contraceptive measures (such measures, for
`patient and sexual partner, include: implants, injectables, combined oral contraceptives,
`intrauterine devices, vasectomized/sterilized partner, use of a double-barrier method or
`sexual abstinence). The patient and his/her parent(s)/legal guardians must be counseled
`on the importance of avoiding pregnancy before or during the study.
`Exclusion Criteria:
`1. The patient and/or parents/caregivers are expected by the Investigator to be non-compliant
`with the study procedures.
`2. Patient has received or is scheduled to receive total body irradiation, total nodal irradiation,
`upper abdomen radiotherapy, half or upper body irradiation, 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 administration on Day 1.
`3. Known history of allergy to any component or other contraindications to any Neurokinin-1
`(NK1) or 5-hydroxytryptamine 3 (5-HT3) receptor antagonists.
`4. Active infection.
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 6/15
`Page 6 of 15
`
`
`
`
`
`
`
`5. Uncontrolled medical condition (e.g., uncontrolled insulin dependent diabetes mellitus).
`6. Patient suffering from ongoing vomiting from any organic etiology (including patients with
`history of gastric outlet obstruction or intestinal obstruction due to adhesions or volvulus,
`patients with a symptomatic central nervous system(CNS) tumor causing nausea and/or
`vomiting) or patient with hydrocephalus.
`7. Patient who experienced any vomiting, retching, or nausea within 24 h prior to the
`administration of the study drug
`8. Patient who received any drug with potential anti-emetic effect within 24 h prior to the start
`of reference chemotherapy, including but not limited to:
`NK1- receptor antagonists (e.g., aprepitant or any other new drug of this class); 5-HT3
`receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron);
`Benzamides (e.g., metoclopramide, alizapride); Phenothiazines (e.g., prochlorperazine,
`promethazine, perphenazine, fluphenazine, chlorpromazine, thiethylperazine);
`Benzodiazepines initiated 48 h prior to study drug administration or expected to be received
`within 120 h following initiation of chemotherapy, except for single doses of midazolam,
`temazepam or triazolam; Butyrophenones (e.g., droperidol, haloperidol); Anticholinergics
`(e.g., scopolamine, with the exception of inhaled anticholinergics for respiratory disorders
`e.g., ipratropium bromide); Antihistamines (e.g., diphenhydramine, cyclizine, hydroxyzine,
`chlorpheniramine, dimenhydrinate, meclizine); Domperidone; Mirtazapine; Olanzapine;
`Prescribed cannabinoids (e.g., tetrahydrocannabinol, nabilone); Over the Counter (OTC)
`antiemetics, OTC cold or OTC allergy medications; Herbal preparations containing ephedra
`or ginger.
`9. Patient who received palonosetron within 1 week prior to administration of study drug.
`10. Patient who has been started on systemic corticosteroid therapy within 72 h prior to study
`drug administration or is planned to receive a corticosteroid as part of the chemotherapy
`regimen
`11. Patient aged < 6 years who received any investigational drug (defined as a medication with
`no marketing authorization granted for any age class and any indication) within 90 days
`prior to Day 1, or patient aged 6 years who received any investigational drug within 30 days
`prior to Day 1 or is expected to receive investigational drugs prior to study completion.
`12. Intake of alcohol, food or beverages (e.g., grapefruit, cranberry, pomegranate and aloe vera
`juices, German chamomile) known to interfere with either CYP3A4 or CYP2D6 metabolic
`enzymes within 1 week prior to Day 1 and during the overall study period.
`13. Use of any drugs or substances known to be strong or moderate inhibitors of CYP3A4 and
`CYP2D6 enzymes within 1 week prior to Day 1 or planned to be used during the overall
`study period.
`14. Use of any drugs or substances known to be CYP3A4 substrates with narrow therapeutic
`range within 1 week prior to Day 1, or planned to be used during the overall study period.
`15. Use of any drugs or substances known to be inducers of CYP3A4 enzymes within 4 weeks
`prior to Day 1 or planned to be used during the overall study period.
`16. Lactating female patient.
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 7/15
`Page 7 of 15
`
`
`
`
`
`
`
`17. Patient with clinically relevant abnormal laboratory values that in the Investigator's opinion
`jeopardize the patient's safety during the study.
`18. Patient aged < 2 years with known hepatic impairment (any grade), or patient aged 2 years
`with known severe hepatic impairment.
`19. Patient aged < 2 years with known renal impairment (any grade), or patient aged 2 years
`with known severe renal impairment.
`20. Enrolment in a previous study with netupitant (either alone or in combination with
`palonosetron).
`Ages Eligible for Study
`up to 17 Years (Child)
`Sexes Eligible for Study
`All
`Accepts Healthy Volunteers
`No
`Study Plan
`This section provides details of the study plan, including how the study is designed and what the study
`is measuring.
`How is the study designed?
`Design Details
`Primary Purpose : Prevention
`Allocation : Randomized
`Interventional Model : Parallel Assignment
`Masking : Triple (Participant, Care Provider, Investigator)
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 8/15
`Page 8 of 15
`
`
`
`
`
`
`
`Arms and Interventions
`Participant Group/ArmIntervention/Treatment
`Experimental:
`Netupitant 1.33 mg/kg
`plus Palonosetron
`Single oral dose of
`Netupitant 1.33 mg/kg
`up to a maximum of
`100 mg (for patients < 3
`months of age the
`netupitant dose will be
`0.8 mg/kg)
`administered with
`single oral dose of 20
`μg/kg palonosetron up
`to a maximum of 1.5
`mg.
`Drug: Netupitant
`Netupitant 1.33 mg/kg oral suspension up to
`a maximum of 100 mg
`Drug: Palonosetron
`Palonosetron 20 μg/kg solution for oral use
`up to a maximum of 1.5 mg
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 9/15
`Page 9 of 15
`
`
`
`
`
`
`
`What is the study measuring?
`Primary Outcome Measures
`Experimental:
`Netupitant 4 mg/kg plus
`Palonosetron
`Single oral dose of
`Netupitant 4 mg/kg up
`to a maximum of 300
`mg (for patients < 3
`months of age the
`netupitant dose will be
`2.4 mg/kg)
`administered with
`single oral dose 20
`μg/kg palonosetron up
`to a maximum of 1.5
`mg.
`Drug: Netupitant
`Netupitant 4 mg/kg oral suspension up to a
`maximum of 300 mg
`Drug: Palonosetron
`Palonosetron 20 μg/kg solution for oral use
`up to a maximum of 1.5 mg
`Outcome
`Measure Measure Description Time
`Frame
`Area Under the
`Plasma
`Concentration
`Versus Time
`Curve From
`Time Zero to
`Infinity (AUC0-
`inf) of
`Netupitant
`Mean values of area under the plasma
`Concentration versus time curve from time
`zero to infinity (AUC0-inf) of netupitant after a
`single oral netupitant administration,
`concomitantly with oral palonosetron, in
`pediatric cancer patients receiving HEC or MEC
`cycles. AUC estimates are obtained by non-
`compartmental analysis of population model-
`predicted individual plasma concentration-time
`profiles.
`within
`168
`hours
`after
`netupita
`nt
`adminis
`tration.
`A
`samplin
`g
`window
`s
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 10/15
`Page 10 of 15
`
`
`
`
`
`
`
`approac
`h will be
`used by
`collecti
`ng a
`single
`blood
`sample
`from
`each
`patient
`in one
`of these
`time
`window
`s: from
`2 to 8 h,
`from 24
`to 48 h,
`from 72
`to 96 h
`and
`from
`120 to
`168 h.
`Maximum
`Plasma
`Concentration
`(Cmax) of
`Netupitant
`Mean values of maximum plasma
`concentration (Cmax) of netupitant after a
`single oral netupitant administration,
`concomitantly with oral palonosetron, in
`pediatric cancer patients receiving HEC or MEC
`cycles. Cmax estimates are obtained by non-
`compartmental analysis of population model-
`predicted individual plasma concentration-time
`profiles
`within
`168
`hours
`after
`netupita
`nt
`adminis
`tration.
`A
`samplin
`g
`window
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 11/15
`Page 11 of 15
`
`
`
`
`
`
`
`s
`approac
`h will be
`used by
`collecti
`ng a
`single
`blood
`sample
`from
`each
`patient
`in one
`of these
`time
`window
`s: from
`2 to 8 h,
`from 24
`to 48 h,
`from 72
`to 96 h
`and
`from
`120 to
`168 h
`Exposure -
`Response
`Analysis for
`Netupitant
`Exposure - Response analysis for netupitant
`performed by assessing the relationships
`between exposure parameters AUC0-inf and
`Cmax with the primary efficacy endpoint, i.e.,
`the CR in the delayed phase.
`Graphical exposure-response analysis for
`netupitant performed by assessing the
`relationship between individual exposure
`parameters (AUC0-inf) and Cmax) with the
`> 24-
`120
`hours
`after
`the
`start of
`chemot
`herapy
`on Day
`1
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 12/15
`Page 12 of 15
`
`
`
`
`
`
`
`Secondary Outcome Measures
`Collaborators and Investigators
`This is where you will find people and organizations involved with this study.
`Helsinn Healthcare SA
`Study Record Dates
`These dates track the progress of study record and summary results submissions to ClinicalTrials.gov.
`Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure
`they meet specific quality control standards before being posted on the public website.
`Study Registration Dates
`primary efficacy endpoint, i.e the CR in the
`delayed phase.
`Outcome
`Measure Measure Description Time
`Frame
`Percentage of
`Pediatric
`Patients With
`Complete
`Response
`During the
`Delayed Phase
`Percentage of Pediatric Patients with complete
`response (CR, i.e., no emetic episodes and no
`rescue medication) during the delayed phase (>
`24 to 120 h after the start of chemotherapy on
`Day 1) after a single oral netupitant
`administration, concomitantly with oral
`palonosetron, in pediatric cancer patients
`receiving HEC or MEC cycles.
`> 24-
`120
`hours
`after
`the
`start of
`chemot
`herapy
`on Day
`1
`Sponsor
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 13/15
`Page 13 of 15
`
`
`
`
`
`
`
`First Submitted
`2017-06-14
`First Submitted that Met QC Criteria
`2017-06-28
`First Posted
`2017-07-02
`Results Reporting Dates
`Results First Submitted
`2020-09-16
`Results First Posted with QC Comments
`2020-10-12
`Results First Submitted that Met QC Criteria
`2020-12-03
`Results First Posted
`2020-12-07
`Study Record Updates
`Last Update Submitted that met QC Criteria
`2024-06-24
`Last Update Posted
`2024-06-25
`Last Verified
`2020-12
`More Information
`Terms related to this study
`HHS Vulnerability Disclosure
`Additional Relevant MeSH Terms
`Signs and Symptoms, Digestive
`Nausea
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 14/15
`Page 14 of 15
`
`
`
`
`
`
`
`Plan for Individual Participant Data (IPD)
`Drug and device information, study documents, and helpful links
`Vomiting
`Antiemetics
`Autonomic Agents
`Peripheral Nervous System Agents
`Physiological Effects of Drugs
`Gastrointestinal Agents
`Serotonin 5-HT3 Receptor Antagonists
`Serotonin Antagonists
`Serotonin Agents
`Neurotransmitter Agents
`Molecular Mechanisms of Pharmacological Action
`Palonosetron
`Plan to Share Individual Participant Data (IPD)?
`No
`Studies a U.S. FDA-Regulated Drug Product
`Yes
`Studies a U.S. FDA-Regulated Device Product
`No
`Study Protocol and Statistical Analysis Plan(https://cdn.clinicaltrials.gov/large-
`docs/79/NCT03204279/Prot_SAP_001.pdf) [PDF, 3.02MB, 2019-02-11]
`Study Documents Provided by Helsinn Healthcare SA
`8/3/25, 4:04 PM Study Details | PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea a…
`https://clinicaltrials.gov/study/NCT03204279 15/15
`Page 15 of 15
`
`
`
`
`
`
`
`