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    Summary
    EudraCT Number:2015-004167-37
    Sponsor's Protocol Code Number:ZX008-1502
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-11-15
    Trial results View 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 number2015-004167-37
    A.3Full title of the trial
    A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Trial of Two Fixed Doses of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy in Children and Young Adults with Dravet Syndrome
    Sperimentazione multicentrica, randomizzata, in doppio cieco, a gruppi paralleli, controllata verso placebo di due dosi fisse di soluzione orale ZX008 (fenfluramina cloridrato) come terapia supplementare in bambini e giovani adulti affetti dalla sindrome di Dravet
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to evaluate the safety and effectiveness of Fenfluramine as adjunct therapy in children and young adults with Dravet Syndrome
    Studio per valutare la sicurezza e l'efficacia di Fenfluramina come terapia supplementare in bambini e giovani adulti affetti dalla sindrome di Dravet
    A.3.2Name or abbreviated title of the trial where available
    Study to evaluate the safety and effectiveness of Fenfluramine as adjunct therapy in children and yo
    Studio per valutare la sicurezza e l'efficacia di Fenfluramina come terapia supplementare in bambini
    A.4.1Sponsor's protocol code numberZX008-1502
    A.5.4Other Identifiers
    Name:IND NumberNumber:125797
    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 SponsorZOGENIX INTERNATIONAL LTD
    B.1.3.4CountryUnited Kingdom
    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 supportZogenix, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationZogenix, Inc.
    B.5.2Functional name of contact pointAJ Acker
    B.5.3 Address:
    B.5.3.1Street Address5858 Horton Street, Suite 455
    B.5.3.2Town/ cityEmeryville
    B.5.3.3Post codeCA 94608
    B.5.3.4CountryUnited States
    B.5.4Telephone number0015105508331
    B.5.5Fax number0015105508341
    B.5.6E-mailajacker@zogenix.com
    D. IMP Identification
    D.IMP: 1
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/13/1219
    D.3 Description of the IMP
    D.3.1Product nameFenfluramina Cloridrato
    D.3.2Product code ZX008
    D.3.4Pharmaceutical form Oral solution
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFenfluramina Cloridrato
    D.3.9.1CAS number 404-82-0
    D.3.9.2Current sponsor codeZX008
    D.3.9.4EV Substance CodeSUB02115MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.25
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/13/1219
    D.3 Description of the IMP
    D.3.1Product nameFenfluramina Cloridrato
    D.3.2Product code ZX008
    D.3.4Pharmaceutical form Oral solution
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFenfluramina Cloridrato
    D.3.9.1CAS number 404-82-0
    D.3.9.2Current sponsor codeZX008
    D.3.9.4EV Substance CodeSUB02115MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/13/1219
    D.3 Description of the IMP
    D.3.1Product nameFenfluramina Cloridrato
    D.3.2Product code ZX008
    D.3.4Pharmaceutical form Oral solution
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFenfluramina Cloridrato
    D.3.9.1CAS number 404-82-0
    D.3.9.2Current sponsor codeZX008
    D.3.9.4EV Substance CodeSUB02115MIG
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 placeboOral solution
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Dravet syndrome
    Sindrome di Dravet
    E.1.1.1Medical condition in easily understood language
    Dravet syndrome
    Sindrome di Dravet
    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 10073682
    E.1.2Term Dravet syndrome
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate that ZX008 0.8 mg/kg/day is superior to placebo as adjunctive therapy in the treatment of Dravet syndrome in children and young adults based on change in the frequency of convulsive seizures between baseline and the combined Titration and Maintenance Periods (T+M).
    Dimostrare che ZX008 a un dosaggio di 0,8 mg/kg/giorno è superiore rispetto al placebo come terapia supplementare nel trattamento della sindrome di Dravet nei bambini e nei giovani adulti, sulla base della variazione nella frequenza delle crisi convulsive tra il basale e i periodi combinati di titolazione e mantenimento (T+M).
    E.2.2Secondary objectives of the trial
    • To demonstrate that ZX008 0.2 mg/kg/day is superior to placebo as adjunctive therapy in the treatment of Dravet syndrome based on change in the frequency of convulsive seizures between baseline and T+M.
    • To demonstrate that the ZX008 0.2 and 0.8 mg/kg/day dose groups are (independently) superior to placebo on the following endpoints:
    - The proportion of subjects who achieve a ≥40% reduction from baseline in convulsive seizure frequency.
    - The proportion of subjects who achieve a ≥50% reduction from baseline in convulsive seizure frequency.
    - The longest convulsive seizure-free interval.

    Please refer to the Clinical Study Protocol, Section 2 Study Objectives and Endpoints for complete list of Secondary Endpoints
    • Dimostrare che ZX008 a un dosaggio di 0,2 mg/kg/giorno è superiore rispetto al placebo come terapia supplementare nel trattamento della sindrome di Dravet, sulla base della variazione nella frequenza delle crisi convulsive tra il basale e i periodi T+M.
    • Dimostrare che i gruppi ZX008 al dosaggio di 0,2 e 0,8 mg/kg/giorno sono (individualmente) superiori al placebo nei seguenti endpoint:
    - Proporzione di soggetti che raggiungono una riduzione ≥ 40% rispetto al basale nella frequenza delle crisi convulsive.
    - Proporzione di soggetti che raggiungono una riduzione ≥ 50% rispetto al basale nella frequenza delle crisi convulsive.
    - Intervallo di tempo di maggior durata libero da crisi convulsive.
    Si prega di fare riferimento al Protocollo di Studio, Sezione 2 Study Objectives and Endpoints per una lista completa degli Endpoints Secondari
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject is male or non-pregnant, non-lactating female, age 2 to 18 years, inclusive as of the day of the Screening Visit. Female subjects of childbearing potential must not be pregnant or breast-feeding. Female subjects of childbearing potential must have a negative urine pregnancy test. Subjects of childbearing or child-fathering potential must be willing to use medically acceptable forms of birth control (see Section 4.4 of the study protocol), which includes abstinence, while being treated on this study and for 90 days after the last dose of study drug.
    2. Subject must have documented medical history to support a clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs.
    3. Subjects must meet all of the following 5 criteria:
    a. Onset of seizures in the first year of life in an otherwise healthy infant.
    b. A history of seizures that are either generalized tonic-clonic or unilateral clonic or bilateral clonic, and are prolonged.
    c. Initial development is normal.
    d. History of normal brain MRI without cortical brain malformation.
    e. Lack of alternative diagnosis.
    4. Subjects must meet at least one of the following 3 criteria:
    a. Emergence of another seizure type, including myoclonic, generalized tonic-clonic, tonic, atonic, absence and/or focal has developed after the first seizure type.
    b. Prolonged exposure to warm temperatures induces seizures and/or seizures are associated with fevers due to illness or vaccines, hot baths, high levels of activity and sudden temperature changes and/or seizures are induced by strong natural and/or fluorescent lighting, as well as certain visual patterns.
    c. Genetic test results consistent with a diagnosis of Dravet syndrome (pathogenic, likely pathogenic, variant of unknown significance, or inconclusive but unlikely to support an alternative diagnosis.)
    5. Subject must have had ≥4 convulsive seizures (tonic-clonic, tonic, atonic, clonic) per 4-week period for past 12 weeks prior to screening, by parent/guardian report to investigator or investigator medical notes.
    6. All medications or interventions for epilepsy (including KD and VNS) must be stable for at least 4 weeks prior to screening and are expected to remain stable throughout the study.
    7. Subject agrees to provide whole blood sample for a broad epilepsy-related gene testing panel.
    8. Subject has been informed of the nature of the study and informed consent has been obtained from the legally responsible parent/guardian.
    9. Subject has provided assent in accordance with Institutional Review Board (IRB) requirements, if capable.
    10. Subject’s parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability.
    1. Soggetti di sesso maschile o soggetti di sesso femminile non in stato di gravidanza né in fase di allattamento, di età compresa tra 2 e 18 anni al momento della visita di screening. I soggetti di sesso femminile in età fertile non devono essere in stato di gravidanza né in fase di allattamento. Tutti i soggetti di sesso femminile in età fertile devono presentare un test di gravidanza sulle urine negativo. I soggetti in età fertile o in grado di procreare devono essere disposti ad utilizzare metodi di contraccezione accettabili dal punto di vista medico (vedere Paragrafo 4.4), tra cui l’astinenza, durante la partecipazione allo studio e per 90 giorni successivi all’ultima dose del farmaco in studio.
    2 Il soggetto deve presentare un’anamnesi che supporti una diagnosi clinica di sindrome di Dravet, con crisi convulsive non completamente controllate dagli attuali farmaci antiepilettici.
    3. I soggetti devono soddisfare tutti i 5 criteri indicati di seguito:
    a. Comparsa di crisi convulsive nel primo anno di vita in un neonato sano.
    b. Anamnesi di crisi convulsive sia tonico-cloniche generalizzate, sia cloniche unilaterali o cloniche bilaterali, di durata prolungata.
    c. Sviluppo iniziale normale.
    d. Anamnesi di RM cerebrale normale, senza malformazioni corticali.
    e. Assenza di una diagnosi alternativa.
    4. I soggetti devono soddisfare almeno uno dei 3 criteri indicati di seguito:
    a. Insorgenza di un altro tipo di crisi convulsiva, tra cui crisi miocloniche, tonico-cloniche generalizzate, toniche, atoniche, assenze e/o crisi focali, sviluppatasi successivamente al primo tipo di crisi convulsiva.
    b. Le crisi convulsive sono indotte dall’esposizione prolungata a temperature elevate e/o le crisi sono associate a febbre dovuta a malattia o vaccini, bagni caldi, elevati livelli di attività e improvvisi sbalzi di temperatura e/o le crisi convulsive sono indotte da una forte illuminazione naturale e/o di tipo fluorescente, nonché da determinati stimoli visivi.
    c. Risultati delle analisi genetiche coerenti con la diagnosi di sindrome di Dravet (tipo patogeno, similpatogeno, variante di significato sconosciuto oppure non conclusivo ma improbabile quale supporto per una diagnosi alternativa.)
    5. Il soggetto deve avere manifestato ≥ 4 crisi convulsive (tonico-cloniche, toniche, atoniche, cloniche) per periodo di 4 settimane nelle ultime 12 settimane precedenti allo screening, secondo la segnalazione del genitore/tutore allo sperimentatore o le note mediche dello sperimentatore.
    6. Tutti i farmaci o gli interventi per l’epilessia (incluse la dieta chetogenica [DC] e la stimolazione del nervo vago [SNV]) devono essere stabili per almeno 4 settimane prima dello screening e dovrebbero rimanere stabili per tutta la durata dello studio.
    7. Il soggetto accetta di fornire campioni di sangue intero per un ampio pannello di analisi genetiche correlate all'epilessia.
    8. Il soggetto è stato informato della natura dello studio ed è stato ottenuto il consenso informato da parte del genitore/tutore legale responsabile.
    9. Il soggetto, se in grado di farlo, ha fornito l’assenso in conformità ai requisiti del comitato etico (CE).
    10. Il genitore/badante del soggetto intende ed è e in grado di compilare il diario, presentarsi alle visite programmate e gestire la contabilità del farmaco in studio.
    E.4Principal exclusion criteria
    1. Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study medication.
    2. Subject has pulmonary arterial hypertension.
    3. Subject has current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke.
    4. Subject has current or recent history of Anorexia Nervosa, bulimia, or depression within the prior year that required medical treatment or psychological treatment for a duration greater than 1 month.
    5. Subject is at imminent risk of self-harm or harm to others, in the investigator’s opinion, based on clinical interview and/or responses provided on the C-SSRS. Subjects must be excluded if they report suicidal behavior in the past 6 months as measured by the C-SSRS at Screening or Baseline, which includes suicidal ideation with intent and plan (Item #5). If a subject reports suicidal ideation on Item 4 without specific plan, and the investigator feels that the subject is appropriate for the study considering the potential risks, the investigator must document appropriateness for inclusion, and discuss with the parent/caregiver to be alert to mood or behavioral changes, especially around times of dose adjustment.
    6. Subject has a current or past history of glaucoma.
    7. Subjects with moderate or severe hepatic impairment may not be entered. Asymptomatic subjects with mild hepatic impairment (elevated liver enzymes < 3xULN and/or elevated bilirubin <2xULN) may be entered into the study after review and approval by the Medical Monitor in conjunction with the sponsor, with consideration of potential cause, concomitant medications, and other risk factors.
    8. Subject is receiving concomitant therapy with: centrally-acting anorectic agents; monoamine-oxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; atomoxetine, or other centrally-acting noradrenergic agonist; cyproheptadine, and/or CYP 2D6/3A4/2B6 inhibitors/substrates (see Appendix 1 of the study protocol).
    (Note: Short-term medication requirements will be handled on a per case basis by the Medical Monitor.)
    9. Subject is currently receiving or has received stiripentol in the past 21 days prior to Screening.
    10. Subject is currently taking carbamazepine, oxcarbamazepine, eslicarbazepine, phenobarbital, or phenytoin, or has taken any of these within the past 30 days, as maintenance therapy.
    11. Subject is unwilling to refrain from large or daily servings of grapefruits and/or Seville oranges, and their juices beginning with the Baseline Period and throughout the study.
    12. Subject has positive result on urine THC Panel or whole blood CBD at the Screening Visit.
    13. Subject has participated in another clinical trial within the past 30 days.
    14. Subject is currently receiving an investigational product.
    15. Subject is unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
    16. Subject has a clinically significant condition, or has had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to the Screening Visit, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.
    1. Il soggetto ha una nota ipersensibilità alla fenfluramina o a uno qualsiasi degli eccipienti contenuti nel medicinale in studio.
    2. Il soggetto soffre di ipertensione polmonare.
    3. Il soggetto presenta un’anamnesi patologica prossima o remota di malattia cardiovascolare o cerebrovascolare, quale valvulopatia cardiaca, infarto miocardico o ictus.
    4. Il soggetto presenta un’anamnesi patologica prossima o remota di anoressia nervosa, bulimia o depressione sviluppata entro l’anno precedente, che ha richiesto trattamento medico o psicologico di durata superiore a 1 mese.
    5. Sulla base di un colloquio clinico e delle risposte fornite, secondo la scala di valutazione della gravità del rischio di suicidio della Columbia University (Columbia-Suicide Severity Rating Scale, C-SSRS), nell’opinione dello sperimentatore esiste il pericolo immediato che il soggetto possa arrecare danni a se stesso o ad altri. I soggetti devono essere esclusi se allo screening o al basale riferiscono comportamenti suicidi negli ultimi 6 mesi, secondo la valutazione della scala C-SSRS, ivi inclusa l’ideazione suicidaria con intenzione e pianificazione (Elemento N. 5). Se un soggetto riferisce ideazione suicidaria senza una specifica pianificazione, indicata nell’Elemento 4, e lo sperimentatore, considerando i rischi potenziali, ritiene che il soggetto sia idoneo allo studio, lo sperimentatore deve documentare la congruità dell’inclusione e chiedere al genitore/badante di prestare attenzione ai cambiamenti dell’umore o comportamentali, specialmente nei periodi di aggiustamento della dose.
    6. Il soggetto presenta un’anamnesi patologica prossima o remota di glaucoma.
    7. Il soggetto presenta una compromissione epatica di grado moderato o grave. I soggetti asintomatici con compromissione epatica lieve (valori degli enzimi epatici elevati < 3x LSN e/o valori di bilirubina elevati < 2x LSN) possono entrare nello studio dopo l’analisi e l’approvazione da parte del responsabile del monitoraggio medico unitamente allo sponsor, in considerazione delle comorbilità e dei farmaci concomitanti.
    8. Il soggetto sta ricevendo una terapia concomitante a base di agenti anoressizzanti ad azione centrale, inibitori delle monoaminossidasi, qualunque composto ad azione centrale con una quantità clinicamente apprezzabile di proprietà agoniste o antagoniste della serotonina, compresa l’inibizione della ricaptazione della serotonina, atomoxetina o altro agonista noradrenergico ad azione centrale, ciproeptadina e/o inibitori/substrati del citocromo P450 (CYP) 2D6/3A4/2B6 (vedere Allegato 1). (Nota: i requisiti a breve termine relativi al medicinale verranno gestiti su base individuale dal responsabile del monitoraggio medico.)
    9. Il soggetto sta attualmente ricevendo o ha ricevuto stiripentolo negli ultimi 21 giorni precedenti allo screening.
    10. Il soggetto sta attualmente assumendo carbamazepina, oxcarbamazepina, eslicarbazepina, fenobarbital o fenitoina, o ha assunto una di tali sostanze negli ultimi 30 giorni quale terapia di mantenimento.
    11. Il soggetto non intende evitare di consumare porzioni grandi o giornaliere di pompelmo e/o arance amare e i relativi succhi a partire dal periodo basale e per tutta la durata dello studio.
    12. Alla visita di screening, il soggetto presenta risultati positivi per tetraidrocannabinolo (THC) nelle urine o per cannabidiolo (CBD) nel sangue intero.
    13. Il soggetto ha partecipato ad un’altra sperimentazione clinica negli ultimi 30 giorni.
    14. Il soggetto sta attualmente ricevendo un prodotto sperimentale.
    15. Il soggetto non intende o non è in grado di rispettare le visite programmate, il piano di somministrazione del farmaco, le analisi di laboratorio, altre procedure dello studio e le restrizioni previste dallo studio.
    16. Nelle 4 settimane precedenti la visita di screening, il soggetto manifesta una patologia clinicamente significativa, ha manifestato una sintomatologia clinicamente importanti o una malattia clinicamente significativa, diversa dall’epilessia, che potrebbe avere un impatto negativo sulla partecipazione allo studio e la raccolta dei dati dello studio, oppure rappresentare un rischio per il soggetto.
    E.5 End points
    E.5.1Primary end point(s)
    Change in the mean convulsive seizure frequency (MCSF) per 28 days between the Baseline and T+M periods.
    E.5.1.1Timepoint(s) of evaluation of this end point
    During the course of the study
    E.5.2Secondary end point(s)
    - The proportion of subjects who achieve a ≥40% reduction from baseline in convulsive seizure frequency.
    - The proportion achieving a ≥50% reduction in convulsive seizures
    E.5.2.1Timepoint(s) of evaluation of this end point
    Over the T + M period
    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 Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA28
    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
    Australia
    Belgium
    Denmark
    France
    Germany
    Italy
    Korea, Republic of
    Norway
    Spain
    Sweden
    Switzerland
    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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months3
    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 Yes
    F.1.1Number of subjects for this age range: 1
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 182
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 78
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2018-11-15. Yes
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Children and adolescents
    Bambini e adolescenti
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 120
    F.4.2.2In the whole clinical trial 260
    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)
    Patients will be given the opportunity to participate in open label extension study
    Hai pazienti verrà data la possibilità di partecipare allo studio di estensione in aperto
    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 Decision2016-03-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-05-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-07-29
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