8/3/25, 4:03 PM Study Details | Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients W...
`
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`Completed i
`
`Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy
`
`Induced Nausea and Vomiting in Patients With Cancer Undergoing BEAM
`
`Conditioning Regimen Before Stem Cell Transplant
`
`ClinicalTrials.gov ID © nCT03097588
`
`Sponsor @ onsu Knight Cancer Institute
`
`Information provided by (i ) Joseph Bubalo, OHSU Knight Cancer Institute (Responsible Party)
`
`Last Update Posted @ 2021-07-12
`
`Study Details Tab
`Study Overview
`Brief Summary
`This phase Il trial studies how well netupitant and palonosetron hydrochloride work in preventing
`chemotherapy induced nausea and vomiting in patients with cancer undergoing BEAM conditioning
`regimen before stem cell transplant. Chemotherapy, such as carmustine, cytarabine, etoposide, and
`melphalan (BEAM), makes people feel sick to their stomach and causes vomiting. Netupitant and
`palonosetron hydrochloride may reduce the nausea and vomiting caused by the BEAM treatment.
`Detailed Description
`PRIMARY OBJECTIVES:
`I. To assess the efficacy of netupitant and palonosetron hydrochloride (NEPA) to prevent nausea and
`vomiting both during and after a highly emetogenic (BEAM) conditioning regimen for hematopoietic
`https://clinicaltrials.gov/study/NCT03097588 1/13
`HELSINN EXHIBIT 2022
`
`Azurity Pharmaceuticals, Inc. v. Helsinn Healthcare S.A.
`Page 1 of 13 IPR2025-00945
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`8/3/25, 4:03 PM Study Details | Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients W...
`stem cell transplantation (HSCT).
`
`SECONDARY OBJECTIVES:
`I. To differentiate response to NEPA over different phases of chemotherapy-induced nausea.
`OUTLINE:
`
`Within 60 minutes before standard of care BEAM treatment, patients receive netupitant and
`palonosetron hydrochloride orally (PO) on days 1, 3, and 6.
`
`After completion of study treatment, patients are followed up at 14 days.
`Official Title
`
`A Phase Il Clinical Trial of NEPA (Netupitant/Palonosetron) for Prevention of Chemotherapy Induced
`Nausea and Vomiting (CINV) in Patient Receiving the BEAM Conditioning Regimen Prior to
`Hematopoietic Cell Transplantation (HSCT)
`
`Conditions @
`
`Malignant Neoplasm
`
`Intervention / Treatment @
`
`» Drug: Netupitant
`o Drug: Palonosetron Hydrochloride
`o Other: Questionnaire Administration
`
`Other Study ID Numbers @
`
`» NCI-2017-00548 ( Registry Identifier ) (REGISTRY: CTRP (Clinical Trial Reporting Program))
`» STUDY00016288 ( Other Identifier ) (OTHER: OHSU Knight Cancer Institute)
`
`Study Start (Actual) @
`
`2017-04-27
`
`Primary Completion (Actual) @
`
`2020-02-20
`
`Study Completion (Actual) @
`
`2020-03-20
`
`Enroliment (Actual) @
`
`43
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`8/3/25, 4:03 PM Study Details | Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients W...
`Study Type @
`
`Interventional
`
`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.nIm.nih.gov/dailymed/) available for:
`
`Palonosetron (https://dailymed.nlm.nih.gov/dailymed/search.cfm?
`
`labeltype=human&gquery=Palonosetron) Palonosetron
`
`hydrochloride (https://dailymed.nim.nih.gov/dailymed/search.cfm?
`
`labeltype=human&query=Palonosetron+hydrochloride)
`
`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 1 location
`
`United States
`
`Oregon Locations
`
`Portland, Oregon, United States, 97239
`OHSU Knight Cancer Institute
`
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`8/3/25, 4:03 PM Study Details | Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients W...
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`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).
`
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`8/3/25, 4:03 PM Study Details | Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients W...
`Eligibility Criteria
`Description
`Inclusion Criteria:
`
`» Subjects must be undergoing autologous or allogeneic hematopoietic stem cell transplant
`(HSCT) with the BEAM conditioning regimen prior to HSCT
`
`» Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofsky
`Performance Score >= 60%
`
`o Able to swallow oral medications
`
`« Ability to understand and the willingness to sign a written informed consent document
`
`Exclusion Criteria:
`
`« Subjects with known hypersensitivity or other allergic reactions attributed to compounds of
`similar biologic composition to netupitant, palonosetron, dexamethasone, or other agents
`used in the study
`
`« Subjects who are receiving any other investigational agents or have received another
`investigational drug in the last 30 days
`
`» Subjects who have had emesis or required antiemetics in the 48 hours prior to starting the
`BEAM conditioning regimen; patients required to take antipsychotics, appetite stimulants,
`or other medications with antiemetic effects will also be excluded if those medications
`cannot be replaced by therapeutic equivalents
`
`o Female subjects who are pregnant, have a positive serum human chorionic gonadotrophin
`(hCG), or are lactating and intend to breastfeed a child; pregnant women are excluded from
`this study; breastfeeding should be discontinued if the mother is treated with NEPA
`
`» Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral
`therapy are ineligible
`
`« Subjects who have taken a neurokinin antagonist within 14 days prior to beginning the
`BEAM regimen
`
`« Subjects who have a serum creatinine > 2 x upper limit of normal (ULN)
`
`« Subjects with severe renal failure or end stage renal disease (estimated GFR [glomerular
`filtration rate] of < 30 mL/min) as estimated by the Cockcroft-Gault formula
`
`» Subjects with severe hepatic insufficiency (Child Pugh score > 9)
`
`« Subjects who have been reported > 5 alcoholic drinks daily for the last year
`
`» Subjects who have concurrent illness requiring systemic corticosteroid use other than the
`planned dexamethasone during conditioning therapy
`
`« Subjects with gastrointestinal conditions that might result in malabsorption of the study
`drug
`
`» Subjects with a history of anxiety-induced ("anticipatory") nausea and vomiting
`
`« Subjects on strong CYP 3A4 inducers or inhibitors who are unable to have those agents
`replaced with clinical alternatives prior to beginning the study; length of washout period will
`be 7 days; notably, in the case of allogeneic transplant recipients requiring cyclosporine or
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`8/3/25, 4:03 PM Study Details | Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients W...
`tacrolimus, no empiric dose adjustments will be required due to close level monitoring and
`adjustments, that are standard in Oregon Health & Science University (OHSU) protocols
`
`« Subjects unable to discontinue benzodiazepines as antiemetics will not be allowed;
`additional antiemetics will be allowed for rescue but not for prophylaxis
`
`« Subjects with personal or family history of QT prolongation, uncorrected electrolyte
`abnormalities, congestive heart failure, bradyarrhythmia, conduction disturbances and
`those taking antiarrhythmic medicinal products or other medicinal products that lead to QT
`
`prolongation or electrolyte abnormalities; relevant information will be collected as part of
`subject medical history
`
`Ages Eligible for Study @
`
`18 Years and older (Adult, Older Adult)
`
`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 @ : Supportive Care
`
`Allocation @ : N/A
`
`Interventional Model @ : Single Group Assignment
`Masking @ : None (Open Label)
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`Arms and Interventions
`
`Participant Group/Arm
`o
`
`Experimental:
`Supportive care (NEPA)
`
`Within 60 minutes
`before standard of care
`BEAM treatment,
`patients receive
`netupitant and
`palonosetron
`hydrochloride PO on
`days 1, 3, and 6.
`
`Netupitant: 300 mg, QD,
`Given PO Palonosetron
`Hydrochloride: 0.5 mg,
`QD, Given PO
`Questionnaire
`Administration:
`Ancillary studies
`
`Intervention/Treatment ©
`
`Drug: Netupitant
`e 300 mg, Given PO, QD
`
`e QOther Names:
`o CID6451149
`
`o D05152
`
`o RO 67-3189/000
`Drug: Palonosetron Hydrochloride
`
`e 0.5 mg, Given PO, QD
`
`e Other Names:
`o Aloxi
`o RS 25259-197
`
`Other: Questionnaire Administration
`
`e Ancillary studies
`
`What is the study measuring?
`
`Primary Outcome Measures o
`
`Outcome
`
`Time
`
`Measure Description
`
`Measure
`
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`Frame
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`Study Details | Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients W...
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`Complete
`Response (CR)
`Defined as no
`Emesis and no
`Rescue
`Therapy
`
`Number of subjects that reached a complete
`response (CR), defined as having no emesis
`and no rescue therapy.
`
`Secondary Outcome Measures o
`
`Outcome
`Measure
`
`CR (Acute
`Phase)
`
`CR (Delayed
`Phase)
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`Measure Description
`
`Number of subjects that reached a complete
`response (CR), defined as having no emesis
`and no rescue therapy from 0 to 144 hours
`
`(acute phase) of the study drug administration.
`
`Number of subjects that reached a complete
`response (CR), defined as having no emesis
`
`and no rescue therapy from 145 hours up to
`
`264 hours (delayed phase) of the study drug
`administration.
`
`Upto 5
`days
`post
`chemot
`herapy
`
`Time
`Frame
`
`Up to
`144
`hours
`post-
`study
`drug
`adminis
`tration
`on day
`1
`
`From
`145
`hours
`up to
`264
`hours
`post-
`study
`drug
`adminis
`tration
`on day
`1
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`Study Details | Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients W...
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`Complete
`Protection (CP)
`Rate Defined as
`CR Plus no
`Nausea
`
`Other Outcome Measures @
`
`Outcome
`Measure
`
`Number of
`Participants
`With Emetic
`Episodes and
`Received
`Rescue Agents
`
`Number of
`Participants
`With Emetic
`Episodes and
`Received
`Rescue Agents
`(Acute Phase)
`
`Number of
`Participants
`With Emetic
`
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`Number of subjects that reached a complete
`response (CR), defined as having no emesis
`and no rescue therapy from 0 to 264 hours of
`the study drug administration.
`
`Measure Description
`
`The number of participants that had emetic
`episodes and received rescue agents
`(medications).
`
`The number of participants that had emetic
`episodes and received rescue agents
`(medications) (acute phase: for 0 to 144 hours
`timeframe of study drug administration)
`
`The number of participants that had emetic
`episodes and received rescue agents
`
`Up to
`264
`hours
`post-
`study
`drug
`adminis
`tration
`on day
`.
`
`Time
`Frame
`
`Up to
`264
`hours
`
`Up to
`144
`hours
`post-
`study
`drug
`adminis
`tration
`on day
`.
`
`Up to
`24
`hours
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`Study Details | Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients W...
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`Episodes and
`Received
`Rescue Agents
`(Acute Phase)
`
`Number of
`Participants
`With Emetic
`Episodes and
`Received
`Rescue Agents
`(Delayed
`Phase)
`
`Mean Levels of
`Nausea Per Day
`Assessed by
`Chemotherapy
`Induced
`Nausea and
`Vomiting
`Questionnaire
`
`Time to First
`Emesis and
`Time to
`Receiving First
`Rescue
`Medication
`
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`Page 10 of 13
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`(medications) (for 0 to 24 hours timeframe of
`study drug administration)
`
`The number of participants that had emetic
`episodes and received rescue agents
`(medications) during the delayed phase (for
`145 hours up to 264 hours timeframe)
`
`The mean level of nausea per day assessed by
`chemotherapy induced nausea and vomiting
`questionnaire. The full range of nausea level
`score on the questionnaire was from minimum
`value of 0 to a maximum value of 10. 0= no
`nausea or vomiting, and 10= worst nausea and
`vomiting. Higher score means a worse
`outcome.
`
`Will be depicted via Kaplan-Meier curves
`showing the percentage of patients who had
`no emesis or rescue medication use for the
`
`acute and delayed time periods.
`
`post-
`study
`drug
`adminis
`tration
`on day
`.
`
`From
`145
`hours
`up to
`264
`hours
`post-
`study
`drug
`adminis
`tration
`on day
`1
`
`Up to
`11 days
`
`Upto
`264
`hours
`
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`8/3/25, 4:03 PM Study Details | Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients W...
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`Time to Will be depicted via Kaplan-Meier curves Up to
`Receiving First showing the percentage of patients who had 264
`Rescue no emesis or rescue medication use for the hours
`Medication and acute and delayed time periods.
`
`First Emesis
`
`Collaborators and Investigators
`This is where you will find people and organizations involved with this study.
`
`Sponsor @
`
`OHSU Knight Cancer Institute
`
`Collaborators @
`e Helsinn Therapeutics (U.S.), Inc
`
`¢ Oregon Health and Science University
`
`Investigators @
`
`* Principal Investigator: Joseph Bubalo, OHSU Knight Cancer Institute
`
`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.
`
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`Study Registration Dates
`
`First Submitted @
`2017-03-27
`
`First Submitted that Met QC Criteria @
`2017-03-27
`
`First Posted @
`2017-03-31
`
`Results Reporting Dates
`
`Results First Submitted @
`2021-05-08
`
`Results First Submitted that Met QC Criteria @
`2021-05-08
`
`Results First Posted @
`2021-06-03
`
`HHS Vulnerability Disclosure
`
`Study Record Updates
`
`Last Update Submitted that met QC Criteria @
`2021-06-12
`
`Last Update Posted @
`2021-07-12
`
`Last Verified @
`2021-06
`
`More Information
`
`Terms related to this study
`
`Additional Relevant MeSH Terms
`
`Signs and Symptoms, Digestive
`Neoplasms
`Vomiting
`
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`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
`
`Drug and device information, study documents, and helpful links
`
`Studies a U.S. FDA-Regulated Drug Product
`
`Yes
`
`Studies a U.S. FDA-Regulated Device Product
`
`No
`
`Study Documents @ Provided by Joseph Bubalo, OHSU Knight Cancer Institute
`
`« Study Protocol and Statistical Analysis Plan (https://cdn.clinicaltrials.gov/large-
`docs/88/NCT03097588/Prot_SAP_000.pdf) [PDF, 1.25MB, 2018-11-27]
`
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