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    Summary
    EudraCT Number:2015-003512-20
    Sponsor's Protocol Code Number:IN11004
    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:2020-11-05
    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 number2015-003512-20
    A.3Full title of the trial
    A Phase III, Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled Study Comparing the Efficacy and Safety of Gastric Retentive, Controlled Release Accordion Pill¿ Carbidopa/Levodopa (AP-CD/LD) to Immediate Release CD/LD in Fluctuating Parkinson¿s Disease Patients
    Studio di fase III controllato con principio attivo, multicentrico, randomizzato, in doppio cieco, con doppio mascheramento che mette a confronto l'efficacia e la sicurezza della carbidopa/levodopa a rilascio controllato, gastroritentiva Accordion Pill¿ (CD/LD-AP) e la CD/LD a rilascio immediato in pazienti affetti da morbo di Parkinson fluttuante
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical Efficacy & Safety of AP CD/LD in Fluctuating Parkinson¿s Disease
    Efficacia e sicurezza clinica di AP CD/LD nel morbo di Parkinson fluttuante
    A.3.2Name or abbreviated title of the trial where available
    Clinical Efficacy & Safety of AP CD/LD in Fluctuating Parkinson¿s Disease
    Efficacia e sicurezza clinica di AP/ CD/LD nel morbo di Parkinson fluttuante
    A.4.1Sponsor's protocol code numberIN11004
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02605434
    A.5.4Other Identifiers
    Name:IN11004Number:n/a
    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 SponsorINTEC PHARMA LTD
    B.1.3.4CountryIsrael
    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 supportIntec Pharma, Ltd.
    B.4.2CountryIsrael
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIntec Pharma, Ltd.
    B.5.2Functional name of contact pointClinical Affairs
    B.5.3 Address:
    B.5.3.1Street Address12 Hartom St., P.O.Box 45219
    B.5.3.2Town/ cityGerusalemme
    B.5.3.3Post code9777512
    B.5.3.4CountryIsrael
    B.5.4Telephone number0097225864657
    B.5.5Fax number0097225869176
    B.5.6E-maillinda@intecpharma.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 Yes
    D.2.1.1.1Trade name SINEMET 25-100
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme Corp.
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 nameImmediate Release carbidopa/levodopa 25/100 mg
    D.3.2Product code [na]
    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 INNCARBIDOPA
    D.3.9.2Current sponsor coden/a
    D.3.9.4EV Substance CodeSUB06126MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLEVODOPA
    D.3.9.2Current sponsor coden/a
    D.3.9.4EV Substance CodeSUB08468MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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: 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 nameAccordion Pill ¿ Carbidopa/Levodopa 50/400 mg
    D.3.2Product code [na]
    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 INNCARBIDOPA
    D.3.9.2Current sponsor coden/a
    D.3.9.4EV Substance CodeSUB06126MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLEVODOPA
    D.3.9.2Current sponsor coden/a
    D.3.9.4EV Substance CodeSUB08468MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    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 nameAccordion Pill ¿ Carbidopa/Levodopa 50/500 mg
    D.3.2Product code [na]
    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 INNCARBIDOPA
    D.3.9.2Current sponsor coden/a
    D.3.9.4EV Substance CodeSUB06126MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLEVODOPA
    D.3.9.2Current sponsor coden/a
    D.3.9.4EV Substance CodeSUB08468MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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
    D.8 Placebo: 2
    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
    Morbo di Parkinson
    E.1.1.1Medical condition in easily understood language
    Parkinson's Disease
    Morbo di Parkinson
    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 HLT
    E.1.2Classification code 10034005
    E.1.2Term Parkinson's disease and parkinsonism
    E.1.2System Organ Class 100000004852
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLT
    E.1.2Classification code 10034005
    E.1.2Term Parkinson's disease and parkinsonism
    E.1.2System Organ Class 100000004852
    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 safety, tolerability and efficacy of Accordion Pill carbidopa/levodopa compared to Immediate Release carbidopa/levodopa in fluctuating Parkinson's Disease patients.
    Valutare la sicurezza, la tollerabilit¿ e l'efficacia della carbidopa/levodopa Accordion Pill (CD/LD-AP) rispetto alla carbidopa/levodopa a rilascio immediato (CD/LD-RI) in pazienti affetti da morbo di Parkinson fluttuante.
    E.2.2Secondary objectives of the trial
    Not applicable.
    Non applicabile
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives

    Other types of substudies
    Specify title, date and version of each substudy with relative objectives: The gastroscopy sub-study is designed to evaluate the effect of the Accordion Pill on the gastric mucosa and to establish the long-term Accordion Pill tolerability.

    Altre tipologie di sottostudi
    specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Il disegno del sotto-studio sulla gastroscopia mira a valutare l'effetto della AP sulla mucosa gastrica e ad accertarne la tollerabilit¿ a lungo termine.
    E.3Principal inclusion criteria
    1. Subjects must be approved for suitability by an Enrollment Approval
    Committee that is assembled of PD clinical experts.
    2. Able and willing to give written (signed and dated) informed consent,
    which includes compliance with study requirements and restrictions
    prior to admission to the study and adhere to visit schedule and
    available to complete the study.
    3. Men or women 30 years of age and higher at initial screening
    assessment. For the approximately 125 subjects who enter the Gastroscopy sub study,
    the age limits are 30-80 years of age, inclusive, at initial screening
    assessment.
    4. Diagnosed with Parkinson's disease, consistent with UK brain bank
    criteria.
    5. Has a good response to Levodopa and is taking at least 4 doses of a
    Levodopa containing medication (or 3 doses of Rytary) per day during
    waking hours (not including nighttime long acting levodopa) at a stable
    dose for at least 28 days prior to initial screening assessment.
    6. Other Anti-PD treatment (such as dopamine agonists, selective MAO-B
    inhibitors, anticholinergic agents or Amantadine) are permitted if stable
    for at least 28 days prior to study entry and provided they are not
    anticipated to be changed during the course of the study.
    7. Total LD immediate release daily dose of 400 mg to 1300 mg or
    equivalent prior to initial screening assessment. Specifically for Rytary,
    doses up to 1755 mg daily are acceptable.
    8. Able to complete a Hauser Home Diary and can tell the difference
    between "On" and "Off" time.
    a. Achieved at least 75% diary concordance with an approved site
    rater in a 4-hour training session including at least one “Off time”
    assessment.
    b. Returned a valid 2-day practice diary after training has been
    completed. A valid diary record will not have more than 4 invalid
    entries (i.e. double or missed entries)
    9. At least 2.5 hours "Off time" per day during waking hours on Screening
    2-day Practice Hauser Home Diary (morning akinesia should be
    incorporated into the total “Off time” assessment).
    10. Other than PD, the subject is in satisfactory health, as assessed by
    physical examination and screening tests. No clinically significant
    medical, psychiatric or laboratory abnormality that could compromise
    safety or interfere with study procedures in the opinion of either the
    investigator or the Enrollment Approval Committee/Sponsor.
    11. Living in an area that is within 3 hours driving distance from the study
    site or is willing to stay in such a place the night before each study visit.
    Inclusion Criteria for the Gastroscopy Sub-Study:
    Subjects entering the study during the period in which recruitment to the
    gastroscopy sub-study is active will have to comply with the following
    additional requirements:
    1. Men or women between 30 and 80 years of age, inclusive, at screening.
    2. Willingness to undergo two gastroscopies during the study period and to
    sign a separate informed consent form.
    3. No contraindications for sedation / anesthesia.
    1. I soggetti devono essere sottoposti all'approvazione dell'idoneità da parte di un
    comitato di arruolamento composto da esperti clinici specializzati nella MP
    2. Devono essere in grado e disponibili a fornire il consenso informato scritto (firmato e
    datato) che include la conformità con i requisiti e i limiti dello studio prima
    dell'ammissione allo studio, a rispettare il programma delle visite e a completare lo
    studio
    3. Uomini o donne di età pari o superiore a 30 anni al momento della valutazione di
    screening iniziale. Per quanto riguarda i circa 125 soggetti che accedono al sottostudio di
    gastroscopia, i limiti di età sono compresi tra 30 e 80 anni (inclusi) al momento della
    valutazione di screening iniziale
    4. Devono avere ricevuto la diagnosi di malattia di Parkinson, in linea con i criteri della
    banca del cervello britannica
    5. Devono mostrare una buona risposta alla levodopa e devono assumere almeno 4
    dosi di un farmaco contenente levodopa (o 3 dosi di Rytary) al giorno durante le ore di
    veglia (esclusa la levodopa notturna a lungadurata) a dose stabile per almeno 28 giorni
    prima della valutazione di screening iniziale
    6. Sono consentiti altri trattamenti anti-MP (come agonisti della dopamina, inibitori
    selettivi della MAO-B, agenti anticolinergici o amantadina) qualora siano stabili per
    almeno 28 giorni prima dell'ingresso nello studio e a condizione che non se ne preveda la modifica in corso di studio
    7. Dose totale quotidiana di LD a rilascio immediato da 400 mg a 1300 mg o
    equivalente prima della valutazione di screening iniziale. In particolare, per Rytary,
    sono considerate accettabili dosi fino a 1755 mg al giorno.
    8. I soggetti devono essere in grado di compilare il diario di Hauser a domicilio e
    distinguere tra periodo "on" e "off"
    a. Devono avere ottenuto una concordanza del diario almeno del 75% con un
    valutatore approvato del centro durante una sessione di formazione di 4 ore, inclusa
    almeno una valutazione del "periodo off"
    b. Devono restituire un diario di prova di 2 giorni valido al termine della formazione. Un
    diario valido non deve contenere più di 4 inserimenti non validi (ovvero inserimenti
    doppi o mancanti)
    9. Almeno 2,5 ore di "periodo off" al giorno durante le ore di veglia nel diario di Hauser
    di prova di 2 giorni a domicilio allo screening (l'acinesia mattutina deve essere inserita
    nella valutazione del "periodo off" totale).
    10. A parte la MP, il soggetto deve essere in condizioni di salute soddisfacenti valutate
    mediante l'esame obiettivo e gli esami allo screening. Assenza di qualunque anomalia
    medica, psichiatrica o di laboratorio clinicamente significativa che, a parere dello
    sperimentatore o del comitato di approvazione dell’arruolamento/dello sponsor, possa
    compromettere la sicurezza o interferire con le procedure dello studio
    11. Residenza in una zona che consenta di raggiungere il centro dello studio nell'arco di
    3 ore di viaggio o disponibilità a pernottare in zona prima di ogni visita dello studio
    Criteri di inclusione del sottostudio di gastroscopia:
    I soggetti che accedono allo studio durante il periodo in cui è attivo l'arruolamento al
    sottostudio di gastroscopia dovranno risultare conformi ai seguenti requisiti aggiuntivi:
    1. Uomini o donne di età compresa tra 30 e 80 anni (inclusi) allo screening
    2. Disponibilità a sottoporsi a due gastroscopie durante il periodo dello studio e a
    firmare un modulo di consenso informato separato
    3. Nessuna controindicazione a sedazione/anestesia
    E.4Principal exclusion criteria
    General Study Exclusion Criteria:
    1. Participation in another drug clinical trial within 28 days prior to initial screening assessment (calculated from the previous study's last dosing date).
    2. Atypical Parkinsonism (subjects with Parkinsonian features caused by disorder such as multiple system atrophy, progressive supranuclear palsy, dementia with Lewy bodies or multiple brain infarcts).
    3. Significant history of cardiac, pulmonary, hepatic or renal disease or other condition or any major complication/illness which, in the opinion of the investigator, contraindicates his/her participation.
    4. Treatment with COMT inhibitors during the last 14 days prior to initial screening assessment.
    5. Received within 4 weeks prior to initial screening assessment or planning to take during study participation: non-selective monoamine oxidase (MAO) inhibitors.
    6. Previous or planned neurosurgical treatment for PD (e.g., procedures including ablation or deep brain stimulation) during the course of the study.
    7. Significant cognitive impairment as defined by the Mini-Mental State Examination (MMSE) score <26.
    8. Clinically significant psychiatric illness, including major depression (Hamilton Depression Rating Scale-17 = 14). Subjects with a lifetime history of suicidal attempt (including an active attempt, interrupted attempt or aborted attempt).
    9. History of alcohol or substance abuse within the past 2 years.
    10. Unable to swallow large pills (e.g., large vitamin pills).
    11. History of melanoma or suspicious skin lesion which could be a melanoma.
    12. Narrow-angle glaucoma.
    13. History of small bowel or gastric surgery ( except for appendectomy or hernioplasty) or bowel obstruction, diagnosis of small bowel narrowing, diagnosis of Crohn's disease, or frequent nausea or emesis, regardless of etiology which, in the opinion of the investigator contraindicates his/her participation in the study.
    14. Active peptic ulcer disease or a history of peptic ulcer or upper GI bleeding.
    15. Current use of opioids.
    16. Symptomatic gastroparesis with frequent vomiting (at least once a week).
    17. Concomitant use of NSAIDs and oral steroids within the past 90 days.
    18. Allergy to the study drug or any of its excipients, or to Yellow Dye #5 (tartrazine).
    19. Women who are pregnant or nursing. Women of childbearing potential who are not willing to use a medically acceptable method of contraception. Medically acceptable methods of contraception that may be used by the subject and /or partner include, but not limited to: oral contraceptive agents, intrauterine devices (IUDs), implantable contraceptives (e.g., Norplant), transdermal hormonal contraceptives (e.g., Ortho-Evra), and injectable contraceptives (e.g., Depo-Provera), condom and /or diaphragm, diaphragm with vaginal spermicide, surgical sterilization (6 months), or postmenopausal females ( no menstrual period for > 2years) or vasectomy ( > 6 months) . The current contraceptive therapy must be maintained for the duration of the study. Hormonal contraceptive therapy must be a stable dose for at least 90 days prior to first study drug administration.

    Exclusion Criterion for the Gastroscopy Sub-Study:
    Subjects who meet the exclusion criterion listed below will not be eligible for the study during the period of the safety sub-study:
    etc...
    1. Partecipazione a un altro studio clinico farmacologico nei 28 giorni precedenti la valutazione di screening iniziale (calcolati dalla data dell'ultima somministrazione dello studio precedente)
    2.Parkinsonismo atipico (soggetti con caratteristiche parkinsoniane causate da disturbi quali atrofia di sistemi multipla, paralisi sopranucleare progressiva, demenza con corpi di Lewy o infarti cerebrali multipli)
    3. Anamnesi significativa per malattia cardiaca, polmonare, epatica o renale o altra condizione o eventuale complicazione/malattia importante che, a giudizio dello sperimentatore, costituisca una controindicazione alla partecipazione
    4. Trattamento con inibitori delle COMT nei 14 giorni precedenti la valutazione di screening iniziale
    5. Assunzione nelle 4 settimane precedenti la valutazione di screening iniziale, o programmata durante la partecipazione allo studio, di: inibitori non selettivi delle monoaminossidasi (MAO)
    6.Trattamento neurochirurgico per il morbo di Parkinson precedente o pianificato (es. procedure che prevedano l'ablazione o la stimolazione cerebrale profonda) durante il corso dello studio.
    7. Deficit cognitivo significativo definito da un punteggio del Mini-Mental State Examination (MMSE, Esame dello stato mentale) < 26.
    8. Malattia psichiatrica clinicamente significativa, inclusi attacchi psicotici o depressione maggiore con Hamilton Depression Rating Scale-17
    (HAM-D-17, scala per la depressione di Hamilton-17) =14. Soggetti con precedenti tentativi di suicidio nell'arco della vita (incluso un tentativo attivo, interrotto o fallito)
    9. Anamnesi positiva per abuso di alcol o di sostanze psicoattive negli ultimi 2 anni
    10. Incapacità di ingerire pillole di grandi dimensioni (es. grosse pillole vitaminiche)
    11. Anamnesi positiva per melanoma oppure lesione cutanea sospetta che potrebbe essere un melanoma
    12. Glaucoma cronico ad angolo stretto
    13. Anamnesi positiva per intervento chirurgico gastrico o sull'intestino tenue (fatta eccezione per appendicectomia o per ernioplastica) oppure ostruzione intestinale, diagnosi di stenosi dell'intestino tenue, diagnosi di morbo di Crohn, nausea o emesi frequenti, indipendentemente dall'eziologia che, a giudizio dello sperimentatore, costituisca una controindicazione alla partecipazione allo studio
    14. Ulcera peptica in atto o anamnesi positiva per ulcera peptica o sanguinamento del tratto GI superiore
    15. Uso corrente di oppioidi
    16. Soggetti con gastroparesi sintomatica con vomito frequente (almeno una volta alla settimana)
    17. Uso concomitante di farmaci antinfiammatori non steroidei (FANS) e di steroidi orali negli ultimi 90 giorni
    18. Allergia al farmaco dello studio o a uno qualunque dei suoi eccipienti, o al colorante giallo n. 5 (tartrazina)
    19. Donne in gravidanza o in allattamento. Donne in età fertile non disposte a utilizzare un metodo contraccettivo accettabile dal punto di vista medico I metodi contraccettivi accettabili dal punto di vista medico che possono essere utilizzati dal soggetto e/o dal(la) partner comprendono, tra gli altri: astinenza, contraccettivi orali, dispositivi intrauterini (IUD), contraccettivi impiantabili (es. Norplant), contraccettivi ormonali transdermici
    (es. Ortho-Evra) e contraccettivi iniettabili (es. Depo-Provera), preservativo e/o diaframma, diaframma con spermicida vaginale, sterilizzazione chirurgica (6 mesi) o donna in età post-menopausale (assenza di cicli mestruali per > 2 anni) o vasectomia (>6 mesi). La terapia contraccettiva corrente deve essere mantenuta per la durata dello studio. Il dosaggio della terapia contraccettiva ormonale deve essere stabile per almeno 90 giorni prima della prima somministrazione del farmaco in studio
    Criteri di esclusione per il sotto-studio sulla gastroscopia
    soggetti che accedono allo studio durante il periodo di arruolamento attivo al
    sottostudio di gastroscopia e che presentano uno qualunque dei criteri di esclusione
    sotto elencati non saranno ritenuti idonei allo studio:

    etc.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint for this study is the change from baseline
    (Week 5) to EOS (Week 26) in the percentage of daily Off time during waking hours based on 3-days by week average of the Hauser home diaries.
    • L’end point primario di efficacia per questo studio è la variazione della percentuale del tempo off giornaliero durante le ore di veglia tra il basale (settimana 5) e la EOS (settimana 26) sulla base della media dei 3 giorni alla settimana documentati nei diari domestici di Hauser.
    E.5.1.1Timepoint(s) of evaluation of this end point
    End of Study (Week 26)
    EOS (settimana 26)
    E.5.2Secondary end point(s)
    1. Change from baseline to EOS of daily Off time (hours).
    2. Change from baseline to EOS of On time without troublesome
    dyskinesias (hours).
    3. Change from baseline to EOS in the number of daily LD doses
    4. Improvement as recorded on CGI-I (patient and physician).
    5. Change from baseline to EOS of On time with troublesome dyskinesias
    (hours).
    6. Change from baseline to EOS in PDQ-39.
    7. Change from baseline to EOS in the Scales for Outcomes in
    Parkinson's Disease PDSS-2.
    8. Change from baseline to EOS in UPDRS Activities of Daily Living and
    Motor Examination (parts 2 and 3).
    ¿ Variazione del tempo off giornaliero (ore) tra il basale e la EOS.
    ¿ Variazione del tempo on senza discinesie problematiche (ore) tra il basale e la EOS.
    ¿ Variazione del numero delle somministrazioni giornaliere di LD tra il basale e la EOS.
    ¿ Miglioramento registrato sulla Clinical Global Impression-Improvement (CGI-I) (paziente e medico).
    ¿ Variazione del tempo on con discinesie problematiche (ore) tra il basale e la EOS.
    ¿ Variazione del Parkinson¿s Disease Questionnaire, 39 voci (PDQ39) tra il basale e la EOS.
    ¿ Variazione della Parkinson¿s Disease Sleep Scale (PDSS-2) tra il basale e la EOS.
    Variazione della Unified Parkinson's Disease Rating Scale (UPDRS) nelle parti relative alle attivit¿ di vita quotidiana e all'esame della funzione motoria (parti 2 e 3) tra il basale e la EOS
    E.5.2.1Timepoint(s) of evaluation of this end point
    End of Study (Week 26)
    EOS (settimana 26)
    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 No
    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 Yes
    E.8.2.3.1Comparator description
    Immediate Release Carbidopa/Levodopa comparatore
    Immediate Release Carbidopa/Levodopa comparator
    E.8.2.4Number of treatment arms in the trial2
    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 concerned18
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA74
    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
    Bulgaria
    Germany
    Hungary
    Israel
    Italy
    Poland
    Russian Federation
    Slovakia
    Spain
    Ukraine
    United Kingdom
    United States
    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 years1
    E.8.9.1In the Member State concerned months9
    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 months9
    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: 189
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 231
    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 230
    F.4.2.2In the whole clinical trial 420
    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)
    Eligible subjects will have the option to participate in an open-label extension study. Ineligible subjects or those not wishing to enter the open-label extension study will revert to the expected normal treatment of their condition.
    I Soggetti eleggibili avranno la possibilit¿ di partecipare ad uno studio in aperto di estensione. I Soggetti non ammissibili o coloro che non desiderano entrare nello studio in aperto di estensione torneranno al trattamento atteso per la loro condizione.
    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 Decision2016-06-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-03-31
    P. End of Trial
    P.End of Trial StatusCompleted
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