Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   41229   clinical trials with a EudraCT protocol, of which   6756   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2018-002474-52
    Sponsor's Protocol Code Number:AM-125-CL-18-01
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-10-21
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2018-002474-52
    A.3Full title of the trial
    Multicenter randomized controlled phase 2 trial to evaluate AM-125 in the treatment of acute peripheral vertigo following neurosurgery (TRAVERS)
    Sperimentazione multicentrica randomizzata controllata di fase 2 finalizzata a valutare l’AM-125 nel trattamento delle vertigini periferiche acute successive a intervento di neurochirurgia (TRAVERS)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study investigating the safety and effectiveness of intranasal betahistine in patients suffering from vertigo (giddiness) after the removal of a tumor of the balance and hearing nerve
    Studio volto a valutare la sicurezza e l'efficacia della betaistina intranasale nei pazienti che soffrono di vertigini (capogiri) dopo la rimozione di un tumore del nervo acustico e vestibolare
    A.3.2Name or abbreviated title of the trial where available
    TRAVERS
    TRAVERS
    A.4.1Sponsor's protocol code numberAM-125-CL-18-01
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAuris Medical Ltd
    B.1.3.4CountryIreland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAuris Medical AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAuris Medical AG
    B.5.2Functional name of contact pointDirector Translational Research
    B.5.3 Address:
    B.5.3.1Street AddressDornacherstrasse 210
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4053
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number41612101354
    B.5.5Fax number41612011351
    B.5.6E-mailih@aurismedical.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBetavert® N16
    D.3.2Product code [Non applicabile]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBETAISTINA DICLORIDRATO
    D.3.9.1CAS number 5579-84-0
    D.3.9.2Current sponsor codeNon applicabile
    D.3.9.3Other descriptive nameBETAHISTINE DIHYDROCHLORIDE; 2-(2-(Methylamino)ethyl)pyridinedihydrochloride; N-methyl-N-(2-pyridin-2-ylethyl)amine dihydrochloride; Methyl(2-[2- pyridyl]ethyl)amine; N-methyl-2-(pyridin-2-yl)ethanamine dihydrochloride
    D.3.9.4EV Substance CodeSUB25919
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number16
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namebetaistina dicloridrato
    D.3.2Product code [AM-125]
    D.3.4Pharmaceutical form Nasal spray, solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntranasal use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBETAISTINA DICLORIDRATO
    D.3.9.1CAS number 5579-84-0
    D.3.9.2Current sponsor codeAm-125
    D.3.9.3Other descriptive nameBETAHISTINE DIHYDROCHLORIDE; 2-(2-(Methylamino)ethyl)pyridine dihydrochloride; N-methyl-N-(2-pyridin-2-ylethyl)amine dihydrochloride; Methyl(2-[2- pyridyl]ethyl)amine; N-methyl-2-(pyridin-2-yl)ethanamine dihydrochloride
    D.3.9.4EV Substance CodeSUB192701
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namebetaistina dicloridrato
    D.3.2Product code [AM-125]
    D.3.4Pharmaceutical form Nasal spray, solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntranasal use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBETAISTINA DICLORIDRATO
    D.3.9.1CAS number 5579-84-0
    D.3.9.2Current sponsor codeAM-125
    D.3.9.3Other descriptive nameBETAHISTINE DIHYDROCHLORIDE; 2-(2-(Methylamino)ethyl)pyridine dihydrochloride; N-methyl-N-(2-pyridin-2-ylethyl)amine dihydrochloride; Methyl(2-[2- pyridyl]ethyl)amine; N-methyl-2-(pyridin-2-yl)ethanamine dihydrochloride
    D.3.9.4EV Substance CodeSUB192701
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namebetaistina dicloridrato
    D.3.2Product code [AM-125]
    D.3.4Pharmaceutical form Nasal spray, solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntranasal use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBETAISTINA DICLORIDRATO
    D.3.9.1CAS number 5579-84-0
    D.3.9.2Current sponsor codeAM-125
    D.3.9.3Other descriptive nameBETAHISTINE DIHYDROCHLORIDE; 2-(2-(Methylamino)ethyl)pyridine dihydrochloride; N-methyl-N-(2-pyridin-2-ylethyl)amine dihydrochloride; Methyl(2-[2- pyridyl]ethyl)amine; N-methyl-2-(pyridin-2-yl)ethanamine dihydrochloride
    D.3.9.4EV Substance CodeSUB192701
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboNasal spray, solution
    D.8.4Route of administration of the placeboIntranasal use (Noncurrent)
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Treatment of acute peripheral vertigo
    trattamento delle vertigini periferiche acute
    E.1.1.1Medical condition in easily understood language
    Treatment of vertigo (giddiness) after removal of a tumor of the balance and hearing nerve
    Trattamento delle vertigini (capogiri) dopo la rimozione di un tumore del nervo acuto e vestibolare
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10059614
    E.1.2Term Vestibular vertigo
    E.1.2System Organ Class 100000004854
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of Part A is
    a. to explore and provide an estimate of the dose response curve for AM-125, and
    b. to evaluate the efficacy of AM-125 compared to placebo in reducing the symptoms of vestibular dysfunction and accelerating vestibular compensation following neurosurgery.

    The primary objective of Part B is to evaluate the efficacy of two selected doses of AM-125 versus placebo, as determined based on the results from Part A, in reducing the symptoms of vestibular dysfunction and accelerating vestibular compensation following neurosurgery compared to placebo.
    L’obiettivo primario della parte A è quello di:
    a) esaminare e fornire una stima della curva dose-risposta relativa all’AM-125, e
    b) valutare l’efficacia dell’AM-125 rispetto al placebo nell’attenuazione dei sintomi della disfunzione vestibolare e nell’accelerazione della compensazione vestibolare successivamente a intervento di neurochirurgia.

    L’obiettivo primario della parte B è quello di valutare l’efficacia di due dosi selezionate di AM-125 rispetto al placebo nell’attenuazione dei sintomi della disfunzione vestibolare e nell’accelerazione della compensazione vestibolare successivamente a intervento di neurochirurgia
    E.2.2Secondary objectives of the trial
    The secondary objective of Part A is to compare the treatment effect of oral betahistine (open label) versus AM-125 in reducing the symptoms of vestibular dysfunction and accelerating vestibular compensation following neurosurgery.

    The secondary objective of both Part A and Part B is to describe the safety and tolerability of AM-125 in the treatment of acute peripheral vertigo following neurosurgery.
    L’obiettivo secondario della parte A consiste nel mettere a confronto l’effetto del trattamento della betaistina orale (in aperto) rispetto all’AM-125 nella riduzione dei sintomi della disfunzione vestibolare e nell’accelerazione della compensazione vestibolare successivamente a intervento di neurochirurgia.

    L’obiettivo secondario sia della parte A che della parte B consiste nel descrivere la sicurezza e la tollerabilità dell’AM-125 nel trattamento delle vertigini periferiche acute successive a intervento di neurochirurgia.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects have to meet all of the following inclusion criteria to be eligible for enrolment into the study:
    1. Scheduled for neurosurgery (vestibular schwannoma resection, labyrinthectomy or vestibular neurectomy)
    2. Small to moderately large vestibular schwannoma (Koos grade I-III; Samii grade T1-T3b; = 30 mm in diameter in cerebellopontine angle) that does not displace the brainstem, documented by magnetic resonance imaging not older than six months.
    or
    Indication for labyrinthectomy or vestibular neurectomy.
    3. Confirmed vestibular function on both sides (> 6 deg/sec sum of bithermal max. slow phase velocity on the affected side in caloric video/electronystagmography (VNG/ENG) and > 10 deg/sec sum of bithermal max. slow phase velocity on the contralateral side).
    4. Presence of symptoms of acute peripheral vertigo:
    • Subjective symptoms of vertigo (rating of at least "two" in EEV questionnaire question 1: illusion of movement)
    • Spontaneous nystagmus beating towards the contralateral side. SVV deviation > 2.5°from the true vertical.
    5. Age at SV (screening visit) =18 years and =70 years.
    6. Negative urine pregnancy test for women of childbearing potential.
    7. Willing and able to attend the study visits.
    8. Able to read and understand study documents, to complete the relevant questionnaires and rating scales and follow Investigator instructions.
    9. Signed informed consent.
    I soggetti devono rispettare tutti i seguenti criteri di inclusione per poter essere arruolati nello studio:
    1. Intervento di neurochirurgia in programma (resezione dello schwannoma vestibolare, labirintectomia o neurectomia vestibolare).
    2. Schwannoma vestibolare da piccolo a moderatamente esteso (indice Koos I-III; indice Samii T1-T3b; = 30 mm di diametro nell’angolo pontocerebellare) senza spostamento1 del tronco cerebrale, documentato da risonanza magnetica non antecedente i sei mesi.
    o
    Indicazione per labirintectomia o neurectomia vestibolare.
    3. Funzione vestibolare confermata su entrambi i lati (somma > 6 gradi/sec della massima velocità della fase lenta bitermica sul lato interessato in video/elettronistagmografia (VNG/ENG) con prova calorica e somma > 10 gradi/sec della massima velocità della fase lenta bitermica sul lato controlaterale).
    4. Presenza di sintomi di vertigini periferiche acute:
    • Sintomi soggettivi di vertigini (punteggio di almeno “due” nella domanda 1 del questionario EEV: illusione del movimento)
    • Nistagmo spontaneo battente verso il lato controlaterale.
    • Deviazione dalla VVS > 2,5°dalla vera verticale.
    5. Età alla data SV =18 anni e =70 anni. X
    6. Test di gravidanza tramite esame delle urine negativo per le donne potenzialmente fertili2
    7. Disponibile e in grado di partecipare alle visite dello studio
    8. In grado di leggere e comprendere i documenti dello studio, di compilare i questionari previsti e le scale di punteggio e di attenersi alle istruzioni degli sperimentatori.
    9. Consenso informato scritto
    E.4Principal exclusion criteria
    1. Prior radiotherapy (gamma knife, intensity modulated radiation therapy) irradiating the brain-stem with more than 4 Gy.
    2. Any ongoing other peripheral vestibular disorder (e.g. Meniere's disease, benign paroxysmal vertigo, vestibular neuritis) or central vestibular disorder (e.g. vestibular migraine, central vertigo).
    3. Vestibular rehabilitation therapy or presurgical gentamicin therapy (i.e. "pre-habilitation therapy") within the past three months prior to neurosurgery.
    4. Any clinically relevant nasal obstruction or pathology precluding effective and/or safe intranasal delivery.
    5. Diagnosis of phaeochromocytoma.
    6. Ongoing upper respiratory tract infection or allergic rhinitis (symptomatic).
    7. Any treatment with antihistamines, anti-emetics or benzodiazepines that is ongoing or planned during the IMP treatment period.
    8. Any history of clinically relevant drug hypersensitivity, urticaria, or other severe allergic diathesis as well as current moderate or severe allergic disorders or hay fever.
    9. Subjects with diagnosed anxiety disorders, depression, schizophrenia or other significant psychiatric diseases requiring current drug treatment or subjects who required treatment in the previous three months prior to
    enrolment for any of these diseases.
    10. Any clinically relevant respiratory, cardiovascular, neurological disorder (e.g. neurofibromatosis type 2, except vertigo), relevant orthopaedic or visual limitation, relevant abnormality in laboratory test or physical examination or other abnormality that in the opinion of the Investigator or Sponsor may pose a safety risk to a subject in this study, which may confound efficacy or safety assessment, or may interfere with study participation.
    11. Any clinically relevant complication during or after neurosurgery that in the opinion of the Investigator or Sponsor may pose a safety risk to a subject in this study, which may confound efficacy or safety assessment, or may interfere with study participation.
    12. Known hypersensitivity, allergy or intolerance to the study medication or any history of severe, abnormal drug reaction.
    13. History within the past two years or presence of drug abuse or alcoholism.
    14. Women who are breast-feeding, pregnant or who are planning to become pregnant during the study.
    15. Women of childbearing potential who are unwilling or unable to use an effective method of avoiding pregnancy from the SV until the end of the study. Effective methods of avoiding pregnancy are contraceptive methods with a Pearl index of less than 1 used consistently and correctly (including implantable, injectable, oral and transdermal contraceptives, intrauterine devices, or a sterile sexual partner, or being abstinent).
    16. Concurrent treatment with another investigational medicinal product or prior treatment with another investigational medicinal product within
    30 days prior to randomization.
    1. Pregressa radioterapia (gamma knife, radioterapia a intensità modulata) con irraggiamento del tronco cerebrale a oltre 4 Gy.
    2. Qualsiasi altro disturbo vestibolare periferico in corso (ad es. sindrome di Ménière1, vertigine parossistica benigna, neurite vestibolare) o disturbo vestibolare centrale (ad es. emicrania
    vestibolare, vertigine centrale).
    3. Terapia riabilitativa vestibolare o terapia gentamicina prechirurgica (la cosiddetta “terapia di pre-abilitazione”) nei tre mesi antecedenti l’intervento di neurochirurgia.
    4. Qualsiasi occlusione o patologia nasale di rilevanza clinica tale da precludere una somministrazione intranasale efficace e/o sicura.
    5. Diagnosi di feocromocitoma.
    6. Infezione delle vie respiratorie superiori o rinite allergica (sintomatica) in corso.
    7. Qualsiasi trattamento a base di antistaminici, antiemetici o benzodiazepine in corso o in programma durante il periodo del trattamento IMP.
    8. Qualsiasi anamnesi di ipersensibilità ai farmaci di rilevanza clinica, orticaria o altra diatesi allergica grave, oltre a disturbi allergici in corso di entità modesta o grave o febbre da fieno.
    9. Soggetti affetti da disturbi da ansia diagnosticati, depressione, schizofrenia o altra patologia psichiatrica rilevante tale da richiedere una terapia farmacologica in corso o soggetti che hanno necessitato di un trattamento nei tre mesi
    precedenti l’arruolamento per via delle suddette patologie.
    10. Qualsiasi disturbo respiratorio, cardiovascolare o neurologico di rilevanza clinica (ad es. neurofibromatosi tipo 2, tranne vertigini), limitazione ortopedica o visiva rilevante, anomalia rilevante da analisi di laboratorio o esame fisico o
    altra anomalia che, secondo il parere dello Sperimentatore o dello Sponsor, potrebbe costituire un rischio per la sicurezza di un soggetto del presente studio, inficiare la valutazione dell’efficacia o della sicurezza o interferire con la
    partecipazione allo studio.
    11. Qualsiasi complicanza di rilevanza clinica insorta durante o dopo l’intervento di neurochirurgia che, secondo il parere dello Sperimentatore o dello Sponsor, potrebbe costituire un rischio per la sicurezza di un soggetto del presente studio,
    inficiare la valutazione dell’efficacia o della sicurezza o interferire con la partecipazione allo studio.
    12. Condizione nota di ipersensibilità, allergia o intolleranza al farmaco oggetto dello studio o qualsiasi anamnesi di grave reazione anomala a farmaci.
    13. Anamnesi nei due anni precedenti o presenza di abuso di sostanze stupefacenti o alcolismo.
    14. Donne in allattamento, in gravidanza o che hanno in programma una gravidanza durante il periodo dello studio.
    15. Donne potenzialmente fertili non disposte o non in grado di adottare un metodo efficace di prevenzione della gravidanza dalla data SV fino alla fine dello studio. Per metodi efficaci di prevenzione della gravidanza si intendono metodi contraccettivi con indice Pearl inferiore a 1 adottati in modo sistematico e corretto (inclusi i contraccettivi impiantabili, iniettabili, orali e transdermici, dispositivi intrauterini o un partner sessuale sterile, o l’astinenza).
    16. Trattamento concomitante con un altro prodotto medicinale sperimentale o trattamento pregresso con un altro prodotto medicinale sperimentale entro i 30 giorni precedenti la randomizzazione.
    E.5 End points
    E.5.1Primary end point(s)
    Primary efficacy endpoints for Part A:
    • Improvement of time standing on foam (eyes closed) from TV (baseline) to FUV2;
    • Improvement in tandem Romberg test (eyes closed) from TV (baseline) to FUV2.
    Primary efficacy endpoint for Part B:
    Based on the outcome of Part A, one of the two primary efficacy endpoints will be selected as primary efficacy endpoint in Part B. The other one will become a secondary efficacy endpoint in Part B. The selection of the primary endpoint will be based on the relative reliability and sensitivity to change.
    Primary safety endpoint for Part A and B:
    Frequency of occurrence of moderate-severe nasal symptoms at TV or any FUV and overall.
    Endpoint di efficacia primari
    • Aumento del tempo in stazione eretta su tappeto morbido (a occhi chiusi) da TV (basale) a FUV2;
    • Miglioramento nel test di Romberg a tandem (ad occhi chiusi) da TV (basale) a FUV2.
    Sulla base dell'esito della Parte A, uno dei due enpoint primari di efficacia sarà selezionato come endpoint primario di efficacia nella Parte B.
    L'altro diventerà un endpoint di efficacia secondario nella Parte B.
    La selezione dell'endpoint primario si baserà sulla relativa affidabilità e sensibilità al cambiamento.
    Endpoint di sicurezza primario per le Parti A e B:
    Frequenza di comparsa di sintomi nasali moderati a gravi in sede di TV o qualsiasi FUV e nel complesso.
    E.5.1.1Timepoint(s) of evaluation of this end point
    End of Part A for primary efficacy endpoints of Part A.
    End of Part B for primary efficacy endpoints of Part B.
    End of Part A and Part B for primary safety endpoint of Part A and B.
    Fine della parte A per gli endpoint di efficacia primari della Parte A.
    Fine della parte B per gli endpoint di efficacia primari della Parte B.
    Fine della parte A e parte B per l'endpoint di sicurezza primario delle Parti A e B.
    E.5.2Secondary end point(s)
    Secondary efficacy endpoints for Part A and Part B:
    • Improvement of time standing on foam (eyes closed) from TV (baseline) to FUV1, FUV3 and FUV4;
    • Improvement in tandem Romberg test (eyes closed) from TV (baseline) to FUV1, FUV3 and FUV4;
    • Improvement in tandem gait from TV (baseline) to all FUVs;
    • Improvement of subjective visual vertical deviation from TV (baseline) to all FUVs.
    Secondary efficacy endpoints for Part B:
    One of the primary efficacy endpoints for Part A will become a secondary efficacy endpoint:
    • Improvement of time standing on foam (eyes closed) from TV (baseline) to FUV2;
    OR
    • Improvement in tandem Romberg test (eyes closed) from TV (baseline) to FUV2.
    Secondary safety endpoints for Part A and B:
    • Frequency of occurrence of any nasal symptoms at TV or any FUV and overall;
    • Occurrence of adverse events after intranasal administration;
    Secondary safety endpoint for Part A (only):
    • Occurrence of adverse events after oral administration
    Endpoint di efficacia secondari per la Parte A e la Parte B:
    • Aumento della durata in stazione eretta su tappeto morbido (occhi chiusi) da TV (basale) a FUV1, FUV3 e FUV4;
    • Miglioramento nel test di Romberg a tandem (occhi chiusi) da TV (basale) a FUV1, FUV3 e FUV4;
    • Miglioramento nella marcia a tandem da TV (basale) ad ogni FUV;
    • Miglioramento nella deviazione dalla verticale visiva soggettiva da TV (basale) ad ogni FUV.
    Endpoint di efficacia secondari per la Parte B:
    Uno degli endopint di efficacia primari per la Parte A diventerà un endpoint di efficacia secondario:
    • Aumento del tempo in stazione eretta su tappeto morbido (a occhi chiusi) da TV (basale) a FUV2;
    OPPURE
    • Miglioramento nel test di Romberg a tandem (ad occhi chiusi) da TV (basale) a FUV2.
    Endpoint di sicurezza secondari per la Parte A e B:
    • Frequenza di comparsa di sintomi nasali in sede di TV o qualsiasi FUV e nel complesso;
    • Comparsa di eventi avversi dopo somministrazione intranasale;
    Endpoint di sicurezza secondari per la Parte A (soltanto):
    • Comparsa di eventi avversi dopo somministrazione orale
    E.5.2.1Timepoint(s) of evaluation of this end point
    End of Part A for secondary efficacy endpoints of Part A.
    End of Part B for secondary efficacy endpoints of Part B.
    End of Part A and/or Part B for secondary safety endpoints of Part A and B.
    Fine della parte A per gli endpoint di efficacia secondari della parte A.
    Fine della parte B per gli endpoint di efficacia secondari della parte B.
    Fine della parte A e/o della parte B per gli endpoint di sicurezza primari delle Parti A e B.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy No
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    braccio in aperto per il trattamento orale nella Parte A (IMP2)
    Open-label arm for oral treatment in Part A (IMP2)
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial5
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA18
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Canada
    Czech Republic
    France
    Germany
    Italy
    Poland
    Slovakia
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    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
    LSLV
    Ultima visita dell'ultimo soggetto
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 18
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 118
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Medical care after completion the study will be provided by either the study site or by the subject's family practitioner or other as per the local standard.
    L'assistenza medica dopo il completamento dello studio sarà fornita dal centro dello studio o dal medico di famiglia del soggetto o altro secondo lo standard locale.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-05-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-07-28
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA