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    Summary
    EudraCT Number:2014-005630-60
    Sponsor's Protocol Code Number:TOZ-CL05
    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:2022-01-17
    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 number2014-005630-60
    A.3Full title of the trial
    A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study with an Open-Label Phase to Determine the Efficacy and Safety of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients with Parkinson's Disease
    Experiencing End-of-Dose "Wearing-Off" (TOZ-PD)
    Studio multicentrico randomizzato di fase 3, condotto in doppio cieco, controllato con placebo, con una fase in aperto, per stabilire l’efficacia e la sicurezza di Tozadenant come terapia supplementare nei pazienti trattati con Levodopa, con malattia di Parkinson e blocco motorio da fine dose (TOZ-PD)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study with an Open-Label Phase to Determine the Efficacy and Safety of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients with Parkinson's Disease
    Experiencing End-of-Dose "Wearing-Off" (TOZ-PD)
    Studio multicentrico randomizzato di fase 3, condotto in doppio cieco, controllato con placebo, con una fase in aperto, per stabilire l’efficacia e la sicurezza di Tozadenant come terapia supplementare nei pazienti trattati con Levodopa, con malattia di Parkinson e blocco motorio da fine dose (TOZ-PD)
    A.3.2Name or abbreviated title of the trial where available
    TOZ-PD
    TOZ-PD
    A.4.1Sponsor's protocol code numberTOZ-CL05
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02453386
    A.5.4Other Identifiers
    Name:TOZ-PDNumber:Not available
    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 SponsorBIOTIE THERAPIES INC.
    B.1.3.4CountryUnited States
    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 supportBiotie Therapies Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBiotie Therapies Corp.
    B.5.2Functional name of contact pointAntero Kallio
    B.5.3 Address:
    B.5.3.1Street AddressJoukahaisenkatu 6
    B.5.3.2Town/ cityTurku
    B.5.3.3Post code20520
    B.5.3.4CountryFinland
    B.5.4Telephone number+358 2 274 8900
    B.5.5Fax number+358 2 274 8910
    B.5.6E-mailAntero.Kallio@biotie.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 nameTozadenant
    D.3.2Product code SYN115
    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.3.9.1CAS number 870070-55-6
    D.3.9.2Current sponsor codeSYN115
    D.3.9.3Other descriptive nameTOZADENANT
    D.3.9.4EV Substance CodeSUB130095
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    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 placeboTablet
    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 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
    The primary efficacy objective of this study is to demonstrate the efficacy of the A2a receptor antagonist tozadenant in the treatment of levodopa-treated PD patients experiencing end-of-dose "wearing-off", based on the change from Baseline to Week 24 in the number of hours per day spent in the OFF state.
    L'obiettivo primario dello studio è dimostrare l'efficacia di tozadenant, antagonista del recettore A2a, nel trattamento dei pazienti con malattia di Parkinson trattati con levodopa che presentano wearing-off, sulla base della variazione dal basale alla settimana 24 nel numero di ore giornaliere trascorse nella fase OFF.
    E.2.2Secondary objectives of the trial
    The key secondary efficacy objectives of this study are:
    1. To evaluate the effect of tozadenant on good ON time (defined as the sum of ON time without dyskinesia and ON time with non-troublesome
    dyskinesia).
    2. To evaluate the effect of tozadenant on UPDRS Parts II (Activities of Daily Living [ADL] subscale) + III (motor subscale) total scores.
    Principali obiettivi secondari di efficacia (Parte A):
    1. Valutare l!effetto di tozadenant sul periodo ON positivo (definito come la somma di tempo nello fase ON senza discinesia e tempo nella fase ON con discinesia non problematica).
    2. Valutare l'effetto di tozadenant sui punteggi totali della Parte II (sottoscala attività della vita quotidiana [Activities of Daily Living, ADL]) + III (sottoscala funzione motoria) della Scala unificata per la valutazione della malattia di Parkinson
    (Unified Parkinson’s Disease Rating Scale, UPDRS).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Patient understands study requirements and has given his/her written informed consent on an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved consent form.
    • Parkinson's disease diagnosis consistent with UK Parkinson's Disease Society Brain Bank Diagnostic criteria
    • Minimum of 3 years since diagnosis.
    • Meet Hoehn and Yahr PD stage
    • Good response to levodopa
    • Stable regimen of anti-PD medications
    • Patients must have been taking a levodopa-containing anti-PD medication continuously for at least the previous 12 months
    • Patient has documented a minimum amount of Off time.
    • If of childbearing potential (male and female) must use an acceptable method of contraception
    • Il paziente comprende i requisiti dello studio e ha fornito consenso informato scritto su un modulo di consenso approvato dal Comitato etico indipendente (CEI).
    • Diagnosi di morbo di Parkinson conforme ai criteri diagnostici della Parkinson’s Disease Society Brain Bank britannica.
    • La diagnosi risale ad almeno 3 anni prima.
    • Soddisfacimento dello stadio di Hoehn e Yahr per il morbo di Parkinson.
    • Buona risposta alla levodopa.
    • Regime stabile di farmaci anti-morbo di Parkinson.
    • I pazienti devono aver assunto un farmaco anti-morbo di Parkinson contenente levodopa continuamente per almeno i 12 mesi precedenti.
    • Il paziente presenta una quantità minima di tempo Off documentata.
    • Se potenzialmente fertile (entrambi i sessi) deve usare un metodo contraccettivo accettabile.
    E.4Principal exclusion criteria
    • Previous tozadenant study participation
    • Current or recent participation in another study.
    • Secondary or atypical parkinsonism
    • Neurosurgical intervention for PD
    • Patient is taking apomorphine, budipine, istradefylline, tolcapone, or DUOPA™/Duodopa®
    • Treatment with excluded medications
    • Untreated or uncontrolled hyperthyroidism or hypothyroidism
    • Clinically significant out-of-range laboratory
    • MMSE out of range
    • Current episode of major depression (stable treatment for depression is permitted).
    • Recent suicide attempt or suicidal ideation type 4 or type 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS)
    • Women lactating or pregnant
    • Hypersensitivity to any components of tozadenant or excipients
    • Abnormal findings on the physical or neurological examination, or medical history that would make the patient unsuitable for the study
    • History of hepatitis or cholangitis
    • Partecipazione precedente a uno studio su tozadenant.
    • Attuale o recente partecipazione a un altro studio.
    • Parkinsonismo secondario o atipico.
    • Intervento neurochirurgico per morbo di Parkinson.
    • Pazienti che assumono apomorfina, budipina, istradefillina, tolcapone o DUOPA™/Duodopa®.
    • Trattamento con farmaci esclusi.
    • Ipertiroidismo o ipotiroidismo non trattato o non controllato.
    • Esami di laboratorio fuori intervallo clinicamente significativi.
    • MMSE fuori intervallo.
    • Attuale episodio di depressione maggiore (è permesso trattamento stabile per la depressione).
    • Recente tentativo di suicidio o ideazione suicidaria di tipo 4 o tipo 5 secondo la Scala di valutazione della gravità del rischio di suicidio Columbia (Columbia-Suicide Severity Rating Scale, C-SSRS).
    • Donne che allattano o in stato di gravidanza.
    • Ipersensibilità a qualsiasi componente di tozadenant o degli eccipienti.
    • Risultati anomali all’esame obiettivo o neurologico o anamnesi che rende il paziente non adatto allo studio.
    • Anamnesi di epatite o colangite.
    E.5 End points
    E.5.1Primary end point(s)
    Primary Efficacy Endpoint (Part A):
    The primary efficacy endpoint will be the change from Baseline to Week 24 in the number of hours per day spent in the OFF state, as assessed by patient-completed PD diaries and averaged over 3 consecutive days.
    Endpoint di efficacia primario (Parte A):
    L’endpoint di efficacia primario sarà la variazione dal basale alla settimana 24 nel numero di ore giornaliere trascorse nella fase OFF, in base ai diari sulla PD completati dal paziente e sulla media di 3 giorni consecutivi.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Analysis of the Primary Efficacy Variable
    The primary efficacy variable will be the change from Baseline to Week 24 in the number of hours per day spent in the OFF state, as assessed by patient-completed PD diaries and averaged over 3
    consecutive days.
    Analisi della Variabile di Efficacia Primaria:
    La variabile di efficacia primario sarà la variazione dal basale alla settimana 24 nel numero di ore giornaliere trascorse nella fase OFF, in base ai diari sulla PD completati dal paziente e sulla media di 3 giorni consecutivi.
    E.5.2Secondary end point(s)
    Key Secondary Efficacy Endpoints (Part A):
    1. Change from Baseline to Week 24 in the number of hours per day spent in good ON time, defined as the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia.
    2. Change from Baseline to Week 24 on UPDRS Parts II (ADL subscale) + III (motor subscale) total scores.
    Principali endpoint di efficacia secondari (Parte A):
    1. Variazione dal basale alla settimana 24 nel numero di ore giornaliere trascorse nella fase ON positiva, definito come la somma del tempo nello fase ON senza discinesia e tempo nella fase ON con discinesia non problematica.
    2. Variazione alla settimana 24, rispetto al basale, nei punteggi totali della Parte II (sottoscala ADL) + III (sottoscala funzione motoria) della UPDRS.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Analysis of the key Secondary Efficacy Endpoints (Part A):
    1. Change from Baseline to Week 24 in the number of hours per day spent in good ON time, defined as the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia.
    2. Change from Baseline to Week 24 on UPDRS Parts II (ADL subscale) + III (motor subscale) total scores.; Analisi dei principali endpoint di efficacia secondari (Parte A):
    1. Variazione dal basale alla settimana 24 nel numero di ore giornaliere trascorse nella fase ON positiva, definito come la somma del tempo nello fase ON senza discinesia e tempo nella fase ON con discinesia non problematica.
    2. Variazione alla settimana 24, rispetto al basale, nei punteggi totali della Parte II (sottoscala ADL) + III (sottoscala funzione motoria) della UPDRS.
    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 No
    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 concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA32
    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
    Canada
    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 years3
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months6
    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: 158
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 292
    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 state56
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 200
    F.4.2.2In the whole clinical trial 450
    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)
    After trial participation, the patients will receive the most appropriate treatment from their physician.
    Dopo la partecipazione alla Sperimentazione, i pazienti riceveranno il trattamento più appropriato dal loro medico.
    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 Decision2015-09-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-09-23
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-01-12
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