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    Summary
    EudraCT Number:2017-000135-14
    Sponsor's Protocol Code Number:PXT-CL17-001
    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:2020-11-04
    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 number2017-000135-14
    A.3Full title of the trial
    Studio di fase IIa, multicentrico, in doppio cieco, randomizzato, controllato verso placebo, a gruppi paralleli per valutare l'efficacia, la sicurezza e la tollerabilit¿ del trattamento orale con PXT002331 (foliglurax) della durata di 28 giorni nella riduzione delle complicazioni motorie dovute alla terapia con levodopa nei pazienti affetti da malattia di Parkinson che manifestano deterioramento da fine dose e discinesia indotta da levodopa (AMBLED)
    Studio di fase IIa, multicentrico, in doppio cieco, randomizzato, controllato verso placebo, a gruppi paralleli per valutare l'efficacia, la sicurezza e la tollerabilit¿ del trattamento orale con PXT002331 (foliglurax) della durata di 28 giorni nella riduzione delle complicazioni motorie dovute alla terapia con levodopa nei pazienti affetti da malattia di Parkinson che manifestano deterioramento da fine dose e discinesia indotta da levodopa (AMBLED)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to look at how safe, well tolerated, and what effect on the body, study drug PXT002331 has in patients with Parkinson's Disease who are already taking the drug Levodopa
    Studio per valutare quanto il farmaco in studio PXT002331 ¿ sicuro, ben tollerato e quale effetto ha sull'organismo, in pazienti con malattia di Parkinson che stanno gi¿ assumendo il farmaco Levodopa
    A.3.2Name or abbreviated title of the trial where available
    AMBLED Study
    Studio AMBLED
    A.4.1Sponsor's protocol code numberPXT-CL17-001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT00000000
    A.5.3WHO Universal Trial Reference Number (UTRN)U0000-0000-0000
    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 SponsorPREXTON THERAPEUTICS B.V.
    B.1.3.4CountryNetherlands
    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 supportPrexton Therapeutics SA
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPrexton Therapeutic
    B.5.2Functional name of contact pointClinical Trial Information Team
    B.5.3 Address:
    B.5.3.1Street AddressGooimeer 2 35
    B.5.3.2Town/ cityNaarden
    B.5.3.3Post code1411 DC
    B.5.3.4CountryNetherlands
    B.5.4Telephone number0041792196751
    B.5.5Fax number0041225522293
    B.5.6E-mailinfo@prextontherapeutics.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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namefoliglurax
    D.3.2Product code PXT002331
    D.3.4Pharmaceutical form Capsule, hard
    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 INNfoliglurax
    D.3.9.1CAS number 1883329-52-9
    D.3.9.2Current sponsor codePXT002331
    D.3.9.3Other descriptive nameCVD00118-E
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 namefoliglurax
    D.3.2Product code PXT002331
    D.3.4Pharmaceutical form Capsule, hard
    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 INNfoliglurax
    D.3.9.1CAS number 1883329-52-9
    D.3.9.2Current sponsor codePXT002331
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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 placeboCapsule, hard
    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
    Parkinson's Disease
    Malattia di Parkinson
    E.1.1.1Medical condition in easily understood language
    A progressive disease of the nervous system characterised by tremor, muscular rigidity, and slow, imprecise movement.
    Malattia progressiva del sistema nervoso caratterizzata da tremore, rigidit¿ muscolare e movimento lento ed impreciso.
    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 PT
    E.1.2Classification code 10061536
    E.1.2Term Parkinson's disease
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the efficacy of 2 doses of PXT002331 as an adjunct to levodopa in the reduction of OFF time in subjects with PD.
    Valutare l'efficacia di 2 dosi di PXT002331 in aggiunta a levodopa nella riduzione del tempo OFF nei soggetti con PD.
    E.2.2Secondary objectives of the trial
    To assess the effects of 2 doses of PXT002331 as an adjunct to levodopa on LID in subjects with PD.
    To assess the pharmacokinetic profile of PXT002331 in subjects with PD.
    To assess the safety and tolerability of 2 doses of PXT002331 in subjects with PD.
    Valutare gli effetti di 2 dosi di PXT002331 in aggiunta a levodopa sulla LID nei soggetti con PD.
    Valutare il profilo farmacocinetico di PXT002331 nei soggetti con PD.
    Valutare la sicurezza e la tollerabilit¿ di 2 dosi di PXT002331 nei soggetti con PD.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subjects will be:
    1.1. males or females of non-childbearing potential diagnosed after the age of 30 years with idiopathic PD (ie, not induced by drugs or other diseases) as defined by fulfilling Steps 1 and 2 of the United Kingdom (UK) PD Society Brain Bank clinical diagnostic criteria
    1.2. between 35 and 85 years of age, inclusive, at the time of signing informed consent
    2. Subjects will have:
    2.1. a documented medical history of idiopathic PD for at least 3 years
    2.2. disease severity of 2 to 4 on the modified Hoehn and Yahr scale when in the OFF state
    2.3. been treated with a stable regimen of levodopa-containing therapy.
    and should maintain the stability of their therapy throughout the study according to their usual regimen (dose level and frequency). The maximum allowed total levodopa dose must be =1600 mg per day.
    2.3.1. subjects who are on an immediate-release formulation of levodopa-containing therapy, NOT including Apodespan PR (or equivalent), must be receiving at least 3 doses per day and must be on a stable dose for at least 2 weeks prior to the first screening visit.
    2.3.2. subjects who are on a long-acting formulation of levodopa-containing therapy, including Apodespan PR (or equivalent), must be on a stable dose for at least 6 weeks prior to the first screening visit
    2.4. experienced motor fluctuations with wearing off over a period of at least 3 months prior to randomisation, with a minimum daily OFF time of at least 2 hours per 24 hours, while awake (as measured during the Screening Period by subject home diary [Hauser diary] on each of the 3 consecutive days immediately preceding the baseline visit; =2 hours OFF time on each of the 3 days)
    2.5. experienced predictable OFF periods, as assessed at screening and baseline by a MDS UPDRS Part IV B, Question 4.5 rating of 1 or 2
    2.6. experienced LID over a period of at least 3 months prior to randomisation, with a minimum daily ON time with dyskinesia
    (troublesome and/or non troublesome) lasting at least 2 hours per 24 hours, while awake (as measured during the Screening Period by subject home diary [Hauser diary] on each of the 3 consecutive days immediately preceding the baseline visit; =2 hours ON time with dyskinesia on each of the 3 days)
    2.7. experienced significant time spent with LID, as assessed at screening and baseline by MDS UPDRS Part IV A, Question 4.1 score =1
    2.8. experienced impact from LID on daily function, as assessed at screening and baseline by MDS UPDRS Part IV A, Question 4.2 score =2
    2.9. been on a stable regimen of any additional permitted anti-Parkinsonian drugs (ie, peripheral decarboxylase inhibitors, dopamine agonists [except apomorphine], MAO-B inhibitors [except safinamide] or COMT inhibitors) for at least 4 weeks prior to baseline.
    3. Female subjects will be women of non-childbearing potential, defined as follows:
    3.1. permanently sterile following hysterectomy, bilateral salpingectomy, bilateral oophorectomy or confirmed tubal occlusion (not tubal ligation)
    3.2. postmenopausal, defined as at least 12 months post cessation of menses (without an alternative medical cause)
    3.2.1. postmenopausal status will be confirmed with a screening serum follicle stimulating hormone (FSH) level greater than 40 mIU/mL.
    4. Subjects must pass a Hauser diary concordance test, defined as at least 75% concordance in ON/OFF ratings between rater and subject over the 4 assessments made over a 2-hour period. Additionally, subjects must be concordant on at least 1 OFF period and 1 ON period across the 4 assessments.
    5. If needed, in the opinion of the Investigator, subjects must have a caregiver (eg, family member, social worker, case worker or nurse that spends >4 hours/week with the subject) considered reliable by the Investigator in providing support to the subject to ensure compliance with study drug, assessment visits and protocol procedures.
    6. Subjects are able, with or without the help of a caregiver, to understand the purpose and risks of the study and provide signed and dated informed consent and authorisation to use confidential health information in accordance with national and local subject privacy regulations.
    1. I soggetti devono essere:
    1.1. uomini o donne, queste ultime non in grado di procreare, con diagnosi dopo i 30 anni di età di PD idiopatica (ovvero non indotta da farmaci o altre malattie) secondo la definizione data dai punti 1 e 2 dei criteri clinico-diagnostici della UK PD Society Brain Bank
    1.2. di età compresa tra 35 e 85 anni, inclusi, al momento della firma del consenso informato
    2. I soggetti devono soddisfare i seguenti requisiti.
    2.1. Presentare una anamnesi documentata di PD idiopatica da almeno 3 anni.
    2.2. Manifestare un livello di gravità della malattia da 2 a 4 secondo la scala Hoehn e Yahr modificata, quando in stato OFF.
    2.3. Essere stati trattati con un regime stabile di terapia con levodopa e devono continuare il trattamento con la terapia stabile durante lo studio in base al loro regime consueto (livello di dose e frequenza). La dose totale massima consentita di levodopa deve essere =1600 mg al giorno.
    2.3.1. I soggetti trattati al momento con una formulazione a rilascio immediato di terapia con levodopa, AD ESCLUSIONE di Apodespan PR (o equivalente), devono ricevere almeno 3 dosi al giorno e devono essere in trattamento con una dose stabile da almeno 2 settimane prima della prima visita di screening.
    2.3.2. I soggetti trattati al momento con una formulazione a rilascio prolungato di terapia con levodopa, incluso Apodespan PR (o equivalente), devono essere in trattamento con una dose stabile da almeno 6 settimane prima della prima visita di screening.
    2.4. Aver manifestato fluttuazioni motorie con deterioramento nell'arco di un periodo di almeno 3 mesi prima della randomizzazione, con un tempo OFF giornaliero minimo di almeno 2 ore ogni 24 ore, durante la veglia (misurato durante il periodo di screening tramite il diario del soggetto [diario Hauser] a uso domiciliar in ciascuno dei 3 giorni consecutivi immediatamente precedenti la visita basale; =2 ore di tempo OFF in ciascuno dei 3 giorni)
    2.5. Aver manifestato periodi OFF prevedibili, in base alla valutazione effettuata allo screening e al basale mediante MDS—UPDRS Parte IV B, domanda 4.5 punteggio di 1 o 2
    2.6. Aver manifestato LID nell'arco di un periodo di almeno 3 mesi prima della randomizzazione, con un tempo ON giornaliero minimo di discinesia (problematica e/o non problematica) della durata di almeno 2 ore ogni 24 ore, durante la veglia (misurato durante il periodo di screening tramite il diario del soggetto [diario Hauser] a uso domiciliare in ciascuno dei 3 giorni consecutivi immediatamente precedenti la visita basale; =2 ore di tempo ON con discinesia in ciascuno dei 3 giorni)
    2.7. Aver trascorso un periodo significativo con LID, secondo la valutazione effettuata allo screening e al basale mediante MDS—UPDRS Parte IV A, domanda 4.1 punteggio =1
    2.8. Aver manifestato un impatto causato da LID sulla capacità di svolgere le attività quotidiane, secondo la valutazione effettuata allo screening e al basale mediante MDS—UPDRS Parte IV A, domanda 4.2 punteggio =2
    2.9. Aver ricevuto un regime stabile di altri farmaci anti-Parkinson consentiti (ossia inibitori della decarbossilasi periferica, agonisti della dopamina [eccetto apomorfina], inibitori delle MAO-B [eccetto safinamide] o inibitori delle COMT) per almeno 4 settimane prima del basale.
    3. Le donne partecipanti non devono essere in grado di procreare così come descritto di seguito:
    3.1. sterili in modo permanente a seguito di isterectomia, salpingectomia bilaterale, ovariectomia bilaterale o occlusione tubarica confermata (non legatura delle tube);
    3.2. in postmenopausa, definita come almeno 12 mesi dopo la cessazione delle mestruazioni (senza una causa medica alternativa).
    3.2.1. Lo stato di postmenopausa sarà confermato da un livello superiore a 40 mUI/ml dell'ormone follicolo-stimolante (FSH) nel siero allo screening.
    4. I soggetti devono superare un test della concordanza del diario Hauser, definita come una concordanza di almeno il 75% nelle valutazioni del tempo ON/OFF tra il valutatore e il soggetto nelle 4 valutazioni effettuate nel corso di un periodo di 2 ore. Inoltre, i soggetti devono essere concordi su almeno 1 periodo OFF e 1 periodo ON nelle 4 valutazioni.
    5. Se necessario, a giudizio dello sperimentatore, i soggetti devono avere una persona che li assista (ad es., familiare, assistente sociale, badante o infermiere che trascorra > 4 ore/settimana con il soggetto) considerata affidabile dallo sperimentatore nel fornire supporto al soggetto al fine di garantire la conformità con il farmaco dello studio, le visite di valutazione e le procedure del protocollo.
    6. I soggetti devono essere in grado, con o senza l'aiuto di una persona che li assiste, di comprendere lo scopo e i rischi dello studio e fornire il consenso informato firmato e datato e l'autorizzazione a utilizzare le informazioni sanitarie riservate in conformità alle normative nazionali e alle disposizioni locali in materia di riservatezza dei soggetti partecipanti a studi clinici.
    E.4Principal exclusion criteria
    1. Subjects with atypical, secondary or drug-induced Parkinsonism (eg, metoclopramide, flunarizine), metabolic identified neurogenetic disorders (eg, Wilson's disease), encephalitis, or Parkinson Plus syndromes, or other forms of atypical Parkinsonian syndromes (eg, progressive supranuclear palsy and multiple system atrophy)
    2. Subjects with a Mini-Mental State Examination (MMSE) score <25
    3. Subjects who have Long QT syndrome or a QTcF >450 ms (males) or > 470 ms (females) that is considered clinically significant by the Investigator at screening or baseline
    4. Subjects who have, or who have a history of, any clinically significant hepatic or gallbladder disorder, as determined by the Investigator
    5. Subjects who have dementia, currently active psychosis or hallucinations. Previous psychotic episodes that were brief and considered drug-induced are not exclusionary; inclusion of such subjects is at the Investigator's discretion.
    6. Suicide attempt within 1 year prior to the first screening visit, or severe suicidal ideation within 6 months prior to the first screening visit (ie, the subject answers "yes" to Questions 4 or 5 in the
    Baseline/Screening C SSRS assessment performed at the first screening visit), or subject is at significant risk of suicidal behaviour in the opinion of the Investigator
    7. Subject has a current diagnosis of epilepsy, has a history of seizures as an adult, has a history of stroke or has had a transient ischemic attack within 1 year prior to the first screening visit
    8. Subjects who have a known genetic disorder of human UDP-glucoronosyltransferase
    9. Any known contraindication to the use of levodopa, including a history of malignant melanoma or a history of narrow-angle glaucoma
    10. Subject has cancer, with the exception of the following: basal cell carcinoma or successfully treated squamous cell carcinoma of the skin; cervical carcinoma in situ; prostatic carcinoma in situ; or other malignancies curatively treated and with no evidence of disease recurrence for at least 3 years
    11. Positive serology test (hepatitis B virus surface antigen [HBsAg], hepatitis C virus [HCV] antibody, human immunodeficiency virus [HIV] 1 or 2 antibodies)
    12. Subjects who have had a clinically significant illness within 4 weeks of first dose, as determined by the Investigator
    13. Subjects with scheduled surgeries during the study period
    14. Any advanced, severe or unstable disease (other than PD) that may interfere with the primary and secondary study outcome evaluations
    15. Subjects who have undergone prior neurosurgical operation for PD or transcranial magnetic stimulation
    16. Subjects currently taking (or expected to be administered during the course of the study) any of the prohibited medications.
    17. Subjects who are participating in another clinical study (eg, attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug (new chemical entity) in the past 3 months prior to the baseline visit
    18. Subjects who have previously taken part in or withdrawn from this study. Re-screening may be permitted on a case-by-case
    basis based on approval from the Sponsor. Re-screening may only be performed once per subject and applies only to screen failures from the study.
    19. Male subjects who do not agree to use a barrier method of contraception (ie, a condom with spermicide) in addition to a second highly effective method of contraception used by their female partners or to refrain from donating sperm from the time of the first dose until 3 months after the final dosing occasion.
    20. Female subjects of childbearing potential
    21. Subjects who have donated:
    21.1. blood in the 3 months prior to the first screening visit
    21.2. plasma in the 7 days prior to the first screening visit
    21.3. platelets in the 6 weeks prior to the first screening visit
    22. Subjects who have a significant history of alcoholism or
    drug/chemical abuse, as determined by the Investigator
    23. Positive test for ethanol or drugs of abuse at the first screening visit or at the baseline visit. The following items would not necessarily be an exclusion to participation in the study, depending on the subject's known use and discussion with the Investigator and medical monitor: cannabinoids, benzodiazepines, barbiturates, opiates, nicotine, and amphetamines for treatment of Attention Deficit Hyperactivity Disorder (ADHD). Use of cocaine, phencyclidine, methadone or amphetamines (for non-medical use) is unconditionally exclusionary.
    24. Subjects who are pregnant (as determined by positive serum pregnancy test at screening and/or positive urine pregnancy test at baseline), breastfeeding or lactating
    25. Subjects who, in the opinion of the Investigator, should not participate in this study
    - Soggetti con Parkinson atipico, secondario o indotto da farmaci (ad es. metoclopramide, flunarizina), disturbi neurogenetici identificati come metabolici (ad es. morbo di Wilson), encefalite o sindromi di Parkinson plus o altre forme di sindromi parkinsoniane atipiche (ad es. paralisi sopranucleare progressiva e atrofia multisistemica).
    - Soggetti con punteggio Mini-Mental State Examination (MMSE) <25
    - Soggetti con sindrome del QT lungo o QTcF >450 ms (uomini) o > 470 ms (donne), considerato clinicamente significativo dallo sperimentatore allo screening o al basale
    - Soggetti con disturbo del fegato o della cistifellea clinicamente significativo in corso o pregresso, come determinato dallo sperimentatore
    - Soggetti con demenza, psicosi attiva o allucinazioni in corso. Precedenti episodi psicotici di breve durata e considerati indotti da farmaci non determinano l'esclusione; l'inclusione di tali soggetti è a discrezione dello sperimentatore
    - Tentativo di suicidio nell'anno precedente la prima visita di screening, o grave ideazione suicidaria nei 6 mesi precedenti la prima visita di screening (cioè, il soggetto risponde "sì" alle domande 4 o 5 alla valutazione C-SSRS al basale/di screening condotta alla prima visita di screening), o il soggetto è a notevole rischio di comportamenti suicidi a giudizio dello sperimentatore
    - Soggetti con diagnosi attuale di epilessia, precedenti convulsioni in età adulta, precedente ictus o attacco ischemico transitorio nell'anno precedente la 1a visita di screening
    - Soggetti con malattia genetica nota di UDP-glucuronosiltransferasi umana
    - Qualsiasi controindicazione nota all'uso di levodopa, compreso un precedente melanoma maligno o precedente glaucoma ad angolo chiuso
    - Soggetti con tumore, a eccezione dei seguenti: carcinoma a cellule basali o carcinoma cutaneo a cellule squamose trattato con successo; carcinoma della cervice in situ; carcinoma prostatico in situ; o altri tumori maligni trattati terapeuticamente e senza evidenza di recidiva della malattia ad almeno 3 anni
    - Analisi sierologiche positive (HBsAg, anticorpi contro HCV, anticorpi controHIV] 1 o 2)
    - Soggetti con una malattia clinicamente significativa entro 4 settimane dalla prima dose, come determinato dallo sperimentatore
    - Soggetti con interventi chirurgici in programma durante il periodo dello studio
    - Qualsiasi malattia avanzata, grave o instabile (diversa da PD) in grado di interferire con le valutazioni degli esiti primari e secondari dello studio
    - Soggetti sottoposti a precedente intervento neurochirurgico per PD o stimolazione magnetica transcranica
    - Soggetti che assumono attualmente uno qualsiasi dei farmaci vietati (o per i quali è prevista una somministrazione nel corso dello studio)
    - Soggetti che partecipano a un altro studio clinico (ad es., che si sottopongono a visite di follow-up) o che hanno partecipato a uno studio clinico con la somministrazione di un farmaco sperimentale (nuova entità chimica) negli ultimi 3 mesi prima della visita basale
    - Soggetti che hanno già partecipato a questo studio o si sono ritirati. Re-screening è permesso caso per caso previa approvazione dello Sponsor. Re-screening può essere effettuato solo una volta per soggetto ed è applicabile solo agli screening failure dello studio.
    - Soggetti di sesso maschile che non accettano di utilizzare un metodo contraccettivo a barriera (ossia un preservativo con spermicida), oltre a un secondo metodo di contraccezione ad alta efficacia utilizzato dalle rispettive partner, o di astenersi dal donare lo sperma a partire dal momento della prima dose e fino a 3 mesi dopo la somministrazione finale
    - Donne in grado di procreare
    - Soggetti che hanno donato:
    - sangue nei 3 mesi precedenti la prima visita di screening; oppure
    - plasma nei 7 giorni precedenti la prima visita di screening; oppure
    - piastrine nelle 6 settimane precedenti la prima visita di screening
    - Soggetti con trascorsi significativi di alcolismo o abuso di sostanze stupefacenti, come determinato dallo sperimentatore
    - Test positivo per l'etanolo o abuso di sostanze stupefacenti alla prima visita di screening o alla visita basale. Le seguenti voci non sarebbero necessariamente motivo di esclusione alla partecipazione allo studio, a seconda dell'uso noto da parte del soggetto e del colloquio con lo sperimentatore e il monitor medico: cannabinoidi, benzodiazepine, barbiturici, oppiacei, nicotina e anfetamine per il trattamento del disturbo da deficit di attenzione e iperattività (ADHD). L'uso di cocaina, fenciclidina, metadone o anfetamine (per uso non medico) determina l'esclusione in modo incondizionato
    - Donne gestanti (come determinato dal test di gravidanza positivo effettuato su siero allo screening e/o al basale) o che allattano al seno
    - Soggetti che, a giudizio dello sperimentatore, non devono partecipare a questo studio
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy outcome measure will be change from baseline to end of Treatment Period (Day 28) in the daily awake OFF time based on subject Hauser diary entries (average of 3 consecutive days).
    L'outcome di efficacia primario sarà misurato come il cambiamento dal basale alla fine del periodo di trattamento (giorno 28) nel tempo OFF giornaliero in stato di veglia, in base alle annotazioni sul diario Hauser da parte del soggetto (media di 3 giorni consecutivi).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline to Day 14
    Baseline to Day 28
    Dal Baseline al Giorno 14
    Dal Baseline al Giorno 28
    E.5.2Secondary end point(s)
    Change from baseline to end of Treatment Period (Day 28) in the total objective score (Parts 3 and 4) for dyskinesia impairment and disability assessed by Unified Dyskinesia Rating Scale (UDysRS)
    ¿ Change from baseline to end of Treatment Period (Day 28) in UDysRS total score
    ¿ Proportion of subjects achieving a clinically significant reduction in OFF time (at least 1 hour as defined by Hauser et al.) from baseline to end of Treatment Period (Day 28) based on subject Hauser diary entries (average of 3 consecutive days)
    ¿ Change from baseline to end of Treatment Period (Day 28) in the percentage of daily awake OFF time based on subject Hauser diary entries (average of 3 consecutive days)
    ¿ Change from baseline to end of Treatment Period (Day 28) in the daily awake ON time without troublesome dyskinesia (defined as ON time without dyskinesia plus ON time with non-troublesome dyskinesia) based on subject Hauser diary entries (average of 3 consecutive days)
    ¿ Change from baseline to end of Treatment Period (Day 28) in the percentage of daily awake ON time without troublesome dyskinesia
    (defined as ON time without dyskinesia plus ON time with non-troublesome dyskinesia) based on subject Hauser diary entries (average of 3 consecutive days)
    ¿ Cambiamento dal basale alla fine del periodo di trattamento (giorno 28) nel punteggio obiettivo totale (Parti 3 e 4) per compromissione e invalidit¿ causate da discinesia valutate secondo la scala UDysRS
    ¿ Cambiamento dal basale alla fine del periodo di trattamento (giorno 28) nel punteggio totale della UDysRS
    ¿ Percentuale di soggetti che raggiungono una riduzione clinicamente significativa del tempo OFF (almeno 1 ora come definito da Hauser et al.) dal basale alla fine del periodo di trattamento (giorno 28) in base alle annotazioni nel diario Hauser da parte del soggetto (media di 3 giorni consecutivi)
    ¿ Cambiamento dal basale alla fine del periodo di trattamento (giorno 28) nel tempo OFF giornaliero in stato di veglia, in base alle annotazioni nel diario Hauser da parte del soggetto (media di 3 giorni consecutivi)
    ¿ Cambiamento dal basale alla fine del periodo di trattamento (giorno 28) nel tempo ON giornaliero in stato di veglia senza discinesia problematica (definita come tempo ON senza discinesia pi¿ tempo ON con discinesia non problematica) in base alle annotazioni nel diario Hauser da parte del soggetto (media di 3 giorni consecutivi)
    ¿ Cambiamento dal basale alla fine del periodo di trattamento (giorno 28) nella percentuale di tempo ON giornaliero in stato di veglia senza discinesia problematica (definita come tempo ON senza discinesia pi¿ tempo ON con discinesia non problematica) in base alle annotazioni nel diario Hauser da parte del soggetto (media di 3 giorni consecutivi)
    E.5.2.1Timepoint(s) of evaluation of this end point
    ¿ Baseline to Day 14
    ¿ Baseline to end of Treatment Period (Day 28)
    ¿ Dal Baseline al Giorno 14
    ¿ Dal Baseline alla fine del periodo di trattamento (Giorno 28)
    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 No
    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 Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    Tollerabilit¿
    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 No
    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 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 concerned14
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA46
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.7Trial has a data monitoring committee No
    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
    The end of the study will be defined as the date of the final clinical database lock. This provides for a single and conservative definition across all study sites (protocol section 15).
    La fine dello studio sar¿ definita come la data del database lock clinico finale. Ci¿ fornisce una definizione singola e prudente per tutti i centri dello studio (sezione 15 del protocollo)
    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 months8
    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 months8
    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: 99
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 66
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state27
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 165
    F.4.2.2In the whole clinical trial 165
    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)
    Standard of care
    Standard di cura
    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 Decision2017-05-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-03-22
    P. End of Trial
    P.End of Trial StatusCompleted
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