E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe Parkinson's disease |
Malattia di Parkinson da moderata a grave |
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E.1.1.1 | Medical condition in easily understood language |
Parkinson's disease |
Malattia di Parkinson |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061536 |
E.1.2 | Term | Parkinson's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029205 |
E.1.2 | Term | Nervous system disorders |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and tolerability of oral istradefylline 20 to 40 mg/d as treatment for subjects with moderate to severe Parkinson¿s Disease (PD). |
Valutare la sicurezza e la tollerabilit¿ a lungo termine di istradefillina orale da 20 a 40 mg/die come trattamento per i soggetti con malattia di Parkinson (Parkinson¿s Disease, PD) da moderata a grave. |
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E.2.2 | Secondary objectives of the trial |
Not applicable |
Non applicabile |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects who have given written informed consent; • Subjects who completed 12 weeks of double-blind treatment and the 30-day follow-up period in Study No. 6002-014; • Subjects who are currently taking levodopa combination carbidopa/levodopa or benserazide/levodopa) therapy plus at least one adjunctive PD medication; • Women of child-bearing potential (WOCBP) must use a reliable method of contraception (e.g., oral contraceptive or long-term injectable or implantable hormonal contraceptive, double barrier methods [such as condom plus diaphragm, condom plus spermicide foam, condom plus sponge], or intra-uterine devices), and must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline. – WOCBP includes any female who has experienced menarche and who has not undergone successful surgical sterilization or is not post-menopausal (defined as amenorrhea = 24 consecutive months or a serum follicle-stimulating hormone [FSH] = 30 IU/L in the absence of hormone replacement therapy. |
• Soggetti che hanno fornito il consenso informato scritto; • Soggetti che hanno completato le 12 settimane di trattamento in doppio cieco e il periodo di follow-up di 30 giorni nello Studio n. 6002-014; • Soggetti che attualmente assumono una terapia combinata con levodopa (carbidopa/levodopa o benserazide/levodopa) più almeno un farmaco aggiuntivo per la PD; • Le donne potenzialmente fertili (Woman of Child-Bearing Potential, WOCBP) devono utilizzare un metodo contraccettivo affidabile (ad es., un contraccettivo orale o un contraccettivo ormonale impiantabile o iniettabile a lungo termine, metodi a doppia barriera [come un preservativo più un diaframma, un preservativo più una schiuma spermicida, un preservativo più una spugna anticoncezionale] o dispositivi intrauterini) e devono presentare un test di gravidanza su siero negativo allo Screening, nonché un test di gravidanza sulle urine negativo al Basale. – Per WOCBP s’intende una qualsiasi persona di sesso femminile che abbia avuto il menarca e che non sia stata sottoposta a sterilizzazione chirurgica con esito positivo o che non sia in post-menopausa (definita come amenorrea per =24 mesi consecutivi o come valore dell’ormone follicolo-stimolante [Follicle-Stimulating Hormone, FSH] sierico =30 UI/l in assenza di una terapia ormonale sostitutiva).
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E.4 | Principal exclusion criteria |
• Subjects whose treatment compliance was less than 70% throughout their enrollment in Study No. 6002-014; • Subjects who are currently treated with apomorphine and/or dopamine receptor antagonists (paliperidone, clozapine, risperidone, olanzapine, quetiapine [except for 100 mg/d or less for levodopa- or PD-induced hallucinations], ziprasidone, aripiprazole, asenapine, and lurasidone, etc.) or direct gastrointestinal levodopa infusion; • Subjects who have been treated within 30 days before Baseline (or five half-lives of the compound, if longer) with any investigational agents other than istradefylline; • Subjects who have undergone a neurosurgical procedure for PD (e.g., pallidotomy, thalamotomy, or deep brain stimulation); • Subjects who are currently receiving another A2A antagonist (except for caffeine which is allowed); • Subjects who are taking potent CYP3A4 inhibitors (systemic antifungals such as ketoconazole); • Subjects who are taking potent CYP3A4 inducers (such as St John’s Wort and rifampin); • Subjects who have had a diagnosis of cancer or evidence of continued malignancy within the past three years (with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or in situ prostate cancer with a normal prostate-specific antigen post resection); • Subjects with major protocol deviations in Study No. 6002-014 (subjects who failed to meet any of the inclusion criteria, subjects who met any of the exclusion criteria or subjects who met the criteria for subject withdrawal but who were not withdrawn); • Subjects who, for any reason, are judged by the Investigator to be inappropriate for this study, including a subject who is unable to communicate or to cooperate with the Investigator or who has/had a clinically significant illness or abnormal physical examination that may compromise the safety of the subject during the study or affect the ability of the subject to adhere to study procedures; • Subjects who have clinical laboratory test results that are clinically unacceptable by the Investigator, or who have an alanine aminotransferase and/or an aspartate aminotransferase level > 3 times the upper limit of normal (ULN), and serum total bilirubin > 2 times the ULN at Screening; • Subjects who have untreated major depressive disorder; • Subjects who have a history of seizures or seizure disorders; • Subjects who have a history of neuroleptic malignant syndrome; • Subjects with suicidal behavior within the previous month; • Subjects who have a history of drug or alcohol abuse or dependence within the last year by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; • Subjects who are pregnant (confirmed by beta human chorionic gonadotropin [ß-HCG]), plan to become pregnant, or are breastfeeding. |
• Soggetti la cui aderenza al trattamento è stata inferiore al 70% durante l’arruolamento nello Studio n. 6002 014; • Soggetti attualmente trattati con apomorfina e/o con antagonisti dei recettori della dopamina (paliperidone, clozapina, risperidone, olanzapina, quetiapina [ad eccezione di 100 mg/die o meno per allucinazioni indotte da levodopa o dalla PD], ziprasidone, aripiprazolo, asenapina e lurasidone, ecc.) o con infusioni gastrointestinali dirette di levodopa; • Soggetti che sono stati trattati con qualsiasi agente sperimentale diverso dalla istradefillina nei 30 giorni precedenti il Basale (o cinque emivite del composto, se di durata maggiore); • Soggetti sottoposti a procedura neurochirurgica per la PD (ad es. pallidotomia, talamotomia o stimolazione cerebrale profonda); • Soggetti attualmente trattati con un altro antagonista dei recettori A2A (ad eccezione della caffeina, che è consentita); • Soggetti che assumono potenti inibitori del CYP3A4 (antimicotici sistemici quali il chetoconazolo); • Soggetti che assumono potenti induttori del CYP3A4 (quali l’iperico e la rifampicina); • Soggetti che hanno ricevuto una diagnosi di cancro o evidenziano presenza di malignità continua nei tre anni precedenti (ad eccezione del carcinoma cutaneo basocellulare o squamocellulare adeguatamente trattato, del carcinoma in situ della cervice, o del carcinoma prostatico in situ con livelli normali di antigene prostatico specifico post-resezione); • Soggetti con deviazioni significative dal protocollo nello Studio n. 6002-014 (soggetti che non hanno soddisfatto uno qualsiasi dei criteri di inclusione, soggetti che hanno soddisfatto uno qualsiasi dei criteri di esclusione o soggetti che hanno soddisfatto i criteri per il ritiro del soggetto, ma che non sono stati ritirati); • Soggetti che, per un qualsiasi motivo, vengono giudicati inadeguati per questo studio da parte dello Sperimentatore, compresi soggetti non in grado di comunicare o collaborare con lo Sperimentatore oppure che presentano/hanno presentato una malattia clinicamente significativa o un esame obiettivo anomalo che potrebbe compromettere la loro sicurezza durante lo studio o influire sulla loro capacità di attenersi alle procedure dello studio; • Soggetti che presentano risultati di esami clinici di laboratorio clinicamente inaccettabili da parte dello Sperimentatore o che mostrano livelli di alanina aminotransferasi e/o aspartato aminotransferasi >3 volte il limite superiore della normalità (Upper Limit of Normal, ULN) e un livello di bilirubina sierica totale >2 volte l’ULN allo Screening; • Soggetti che hanno un disturbo depressivo maggiore non trattato; • Soggetti che hanno un’anamnesi di crisi convulsive o disturbi convulsivi; • Soggetti che hanno un’anamnesi di sindrome neurolettica maligna; • Soggetti con comportamento suicidario nel mese precedente; • Soggetti con un’anamnesi di abuso o dipendenza da alcol o altre sostanze nell’ultimo anno in base a quanto definito nel Manuale Diagnostico e Statistico dei Disturbi Mentali, quarta edizione, testo riveduto (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision); • Soggetti in stato di gravidanza (confermato da beta-gonadotropina corionica umana [Beta Human Chorionic Gonadotropin, ß HCG]), che intendono iniziare una gravidanza o che sono in allattamento.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety: • AEs; • Clinical laboratory assessments. |
Safety: • AEs; • Clinical laboratory assessments. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening, Baseline, Weeks 12, 26, and 52 and 30 day follow up visit |
Screening, Baseline, Weeks 12, 26, and 52 and 30 day follow up visit |
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E.5.2 | Secondary end point(s) |
Efficacy: ¿ Change from Baseline in the score on the PGI-I Scale |
Efficacy: ¿ Change from Baseline in the score on the PGI-I Scale |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 12, 26, and 52. |
Weeks 12, 26, and 52. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open Label Safety |
Open Label Safety |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Israel |
Serbia |
United States |
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E.8.7 | Trial 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
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The end of study is the date of the last telephone follow up of the last study participant. |
The end of study is the date of the last telephone follow up of the last study participant. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 7 |