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    The EU Clinical Trials Register currently displays   41210   clinical trials with a EudraCT protocol, of which   6750   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2016-003961-25
    Sponsor's Protocol Code Number:TOZ-CL06
    National Competent Authority:Czechia - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-05-15
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedCzechia - SUKL
    A.2EudraCT number2016-003961-25
    A.3Full title of the trial
    A Multicenter, Open-Label Study to Evaluate the Safety and Tolerability of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients with Parkinson’s Disease Experiencing End of Dose “Wearing-Off”
    Multicentrická, otevřená studie s cílem vyhodnotit bezpečnost a snášenlivost tozadenantu jako podpůrné terapie u pacientů s Parkinsonovou nemocí léčených levodopou, kteří pociťují ztrátu účinku u horní hranice dávky
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate the safety and tolerability of tozadenant in Parkinson disease patients who are taking levodopa and experiencing "wearing off"
    A.4.1Sponsor's protocol code numberTOZ-CL06
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03051607
    A.5.4Other Identifiers
    Name:IND NumberNumber:78230
    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
    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
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAMS Advanced Medical Services
    B.5.2Functional name of contact pointClinical Operations
    B.5.3 Address:
    B.5.3.1Street AddressAm Exerzierplatz 2
    B.5.3.2Town/ cityMannheim
    B.5.3.3Post code68167
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+4962170095 100
    B.5.5Fax number+4962170095 140
    B.5.6E-mailoperations@ams-europe.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 TOZ
    D.3.4Pharmaceutical form Film-coated 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 INNtozadenant
    D.3.9.1CAS number 870070-55-6
    D.3.9.2Current sponsor codeTOZ
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Parkinson's Disease
    E.1.1.1Medical condition in easily understood language
    Parkinson's Disease
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10013113
    E.1.2Term Disease Parkinson's
    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 evaluate the safety and tolerability of tozadenant in levodopa-treated PD patients experiencing motor fluctuations
    E.2.2Secondary objectives of the trial
    To evaluate the effects of tozadenant on the occurrence of daytime drowsiness, impulsive behavior, and suicidality.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    PK sub-study - not conducted in European sites
    E.3Principal inclusion criteria
    1. Provide written informed consent.
    2. Patient is considered reliable and capable of adhering to the protocol according to the judgment of the investigator.
    3. Patient has a documented history of idiopathic Parkinson’s disease consistent with the UK Parkinson’s Disease Society Brain Bank Diagnostic criteria prior to the Screening Visit.
    4. Patient has a PD duration of at least 3 years from diagnosis.
    5. Patient has a modified Hoehn and Yahr stage 2–4 when in OFF state (estimated) and ≤ 3 in ON state.
    6. Patient is male or female and 30–80 years old (inclusive) at Screening.
    7. Patient must have a good response to levodopa in the opinion of the investigator, be taking at least four doses of a levodopa-containing medication per day, and at least one other concomitant anti PD medication (dopamine agonists, MAO-B inhibitors, anticholinergic agents, amantadine or entacapone).
    8. Patient is maintained on a regimen of permitted anti-PD medications that has been stable for at least 4 weeks prior to Screening.
    9. Patients must have been taking a levodopa-containing anti-PD medication continuously for at least the previous 12 months and must be currently experiencing end-of-dose “wearing-off” with at least 2.5 hours of OFF time per day as confirmed by a 3-day Baseline diary.
    10. Patient must have achieved the following results for PD diary training, practice diary collection, and Baseline diary recordings:
    a. During a diary concordance session with an approved PD diary trainer/rater (minimum 2.5 hours), patient achieved at least 80% overall diary concordance including at least 1 OFF interval.
    b. Returned a valid 3 day (i.e., 3 consecutive 24 hour periods) practice diary.
    c. Returned valid diary recordings for each of the 3 consecutive days preceding the Baseline Visit that indicated at least 2.5 hours of OFF time on each of the 3 days.
    11. Contraception:
    a. Women of childbearing potential must use an acceptable method of contraception starting 4 weeks prior to study drug administration and for a minimum of 1 month after study completion. Otherwise, women must be postmenopausal (at least 1year absence of vaginal bleeding or spotting, and confirmed by follicle stimulating hormone [FSH] ≥ 40 mIU/mL [or ≥ 40 IU/L] if less than 2 years postmenopausal) or be surgically sterile.
    b. Men with a potentially fertile partner must have had a vasectomy or be willing to use an acceptable method of contraception for the duration of the study and for 3 months after study drug discontinuation.
    For men and women: Acceptable methods of contraception include use of a condom with spermicide; oral, implantable or injectable contraceptives; intrauterine device (IUD); diaphragm with spermicide; or, diaphragm with condom.
    E.4Principal exclusion criteria
    1. Patient previously participated in any study with tozadenant.
    2. Patient is currently participating in or has participated in another study and received an IMP within 5 half-lives of the IMP.
    3. Patient has any form of secondary or atypical parkinsonism (e.g., drug-induced, post stroke).
    4. Body mass index (BMI) greater than 40.
    5. QTcF interval of ≥ 500 msec at Screening (Visit 1) or the patient has an average QTcF interval ≥ 450 msec for males or ≥ 470 msec for females at Baseline (Visit 2).
    6. Known diagnosis of malignant melanoma.
    7. History of neurosurgical intervention for PD, except for the placement of deep brain stimulator electrodes at least 12 months or greater prior to screening; subjects with DBS must not be experiencing any clinically meaningful side effects related to the procedure, the device, or stimulation.
    8. Grade 2 hypertension (supine systolic BP ≥ 160 or diastolic BP ≥ 100 mmHg), treated or untreated
    9. Patient with a history of hypertensive crisis unless the underlying cause has been removed (e.g. stenting for renal artery stenosis).
    10. Patient has a history of chronic alcohol or drug abuse within the last 2 years.
    11. Patient is taking apomorphine, budipine, istradefylline, tolcapone, or DUOPA™/Duodopa®, within 4 weeks prior to Screening or is likely to require any of these drugs during the study.
    12. Current treatment with antipsychotics; however, quetiapine administered at doses of ≤ 100 mg per day and pimavanserin are permitted if the patient has been on a stable daily dose for at least 4 weeks before Screening. PRN (as needed) dosing is not permitted.
    13. Patient has taken digoxin within 4 weeks prior to Screening or is likely to require digoxin during the study.
    14. Hyperthyroidism or hypothyroidism, unless all of the following conditions are met:
    a. Patient has received a stable dose of thyroid medication for at least 3 months before the Baseline Visit.
    b. TSH concentrations are in the normal range (± 10% as a window either side of the normal range).
    c. Patient is clinically euthyroid.
    15. Any out-of-range laboratory values at Screening that have not been reviewed and documented as not clinically significant by the investigator.
    16. A score of < 26 on the Mini-Mental State Examination, Second Edition (MMSE-II) at the Screening Visit.
    17. Patients with a current episode of major depression. Patients receiving treatment for depression with antidepressants may be enrolled if they have been on a stable daily dose of the antidepressant for at least 8 weeks before the Baseline Visit.
    18. Patient has a recent history of suicide attempt (defined as an active, interrupted or aborted attempt within the past 5 years), or reports suicidal ideation in the past 6 months as indicated by a positive response (‘Yes’) to either Question 4 or Question 5 of the C-SSRS performed at the Screening or Baseline Visit.
    19. Patient has evidence of an impulse control disorder (ICD) (i.e., one or more positive modules) according to the Modified Minnesota Impulse Disorders Interview (mMIDI) unless a structured clinical interview performed during Screening confirms that the patient does not have an ICD.
    20. Patient is currently lactating or pregnant or planning to become pregnant during the duration of the study.
    21. Patient has a known hypersensitivity to any components of the IMP or excipients.
    22. Any other condition or clinically significant abnormal findings on the physical or neurological examination, psychiatric and medical history, at Screening or at Baseline that, in the opinion of the investigator, would make the patient unsuitable for the study or put the patient at additional risk or prejudice evaluation of safety and efficacy of the IMP.
    23. Patients with alanine transaminase (ALT) or aspartate transaminase (AST) ≥3x upper limit of normal (ULN), or total bilirubin ≥1.5x ULN, at Screening.
    24. Patients with a history of hepatic dysfunction secondary to viral infection (hepatitis B or C; Epstein Barr virus [EBV]; or cytomegalovirus [CMV]), or a history of diagnosed drug- or alcohol-induced hepatic toxicity or frank hepatitis.
    25. Patients with moderate to severe hepatic or renal impairment.
    26. Patients who have taken strong cytochrome P450 subtype 3A4 (CYP3A4) inhibitors or inducers within 4 weeks prior to Baseline (Visit 2) or who anticipate requiring use of strong CYP3A4 inhibitors or inducers during the study
    27. Patients with absolute neutrophil count less than 2000/mm3 (or 2.0 x 10E9/L) at screening
    E.5 End points
    E.5.1Primary end point(s)
    1. Treatment emergent Adverse Events.
    2. Vital signs
    3. ECGs
    4. Clinical Laboratory tests
    5. Physical and neurological examinations
    E.5.1.1Timepoint(s) of evaluation of this end point
    End of treatment, assumed to be 52 weeks
    E.5.2Secondary end point(s)
    Epworth Sleepiness Scale ESS
    modified Minnesota Impulse Disorders Interview mMIDI
    Columbia Suicide Severity Rating Scale C-SSRS
    Unified Parkinson’s Disease Rating Scale (UPDRS) Part I - IV
    Clinical Global Impression of Change (CGI-C).
    Patient’s Global Impression of Change (PGI-C).
    Parkinson’s Disease Quality of Life Questionnaire (PDQ-39; total score and individual domain scores).
    Non-motor Symptom Questionnaire.
    EuroQol 5D-5L Health Questionnaire (EQ-5D-5L).
    Patient-completed diaries (Change from Baseline in the number of hours per day spent as follows: OFF time, ON time without troublesome dyskinesia, total ON time, ON time with troublesome dyskinesia and asleep time).
    Healthcare Resource Utilization.
    Fall Questionnaire
    E.5.2.1Timepoint(s) of evaluation of this end point
    End of treatment, assumed to be 52 weeks
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other No
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA40
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    European Union
    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
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    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 state39
    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)
    Patients will return to standard of care under their neurologists
    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 Decision2017-09-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-06-14
    P. End of Trial
    P.End of Trial StatusOngoing
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