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    The EU Clinical Trials Register currently displays   42891   clinical trials with a EudraCT protocol, of which   7066   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2007-004322-24
    Sponsor's Protocol Code Number:OV-1012
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2008-11-03
    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 ConcernedBulgarian Drug Agency
    A.2EudraCT number2007-004322-24
    A.3Full title of the trial
    Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Clobazam (0.25, 0.5 and 1.0 mg/kg/day) in Patients with Lennox-Gastaut Syndrome.
    A.4.1Sponsor's protocol code numberOV-1012
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorOvation Pharmaceuticals 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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 Clobazam
    D.2.1.1.2Name of the Marketing Authorisation holderSanofi-Aventis Deutschland GMBH
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameClobazam Tablets 5mg
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNClobazam
    D.3.9.1CAS number 22316-47-8
    D.3.9.3Other descriptive nameClobazam PhEur
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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) Information not present in EudraCT
    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 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 Information not present in EudraCT
    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 Information not present in EudraCT
    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
    Lennox-Gastaut Syndrome
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10048816
    E.1.2Term Lennox-Gastaut syndrome
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    1. To determine the efficacy of clobazam (CLB) in the reduction of drop seizures at three
    dose levels when compared to baseline during 12 weeks maintenance dosing in a
    placebo controlled trial in patients with Lennox-Gastaut Syndrome (LGS).
    2. To determine the safety of CLB when administered for up to 18 weeks at three different
    dose levels in patients with LGS.
    E.2.2Secondary objectives of the trial
    1. To determine the efficacy of CLB as determined by responder rates and global
    evaluation of patient symptoms.
    2. To determine population pharmacokinetic (PPK) parameters of CLB and its active
    metabolite N-desmethylclobazam (N-CLB) at steady-state dosing of CLB in patients
    with LGS and to describe sources of inter-patient variability (co-variates) including
    patient demographics, concomitant antiepileptic drug (AED) medications and genotype.
    3. To evaluate the development of tolerance during treatment for up to 12 weeks.
    4. To determine the effect of CLB on behavior utilizing the Child Behavior Checklist
    (CBCL).
    5. To determine the impact of CLB on behavioral, cognitive and physical/neurologic
    disability through use of the Impact of Childhood Neurologic Disability Scale (ICNDS).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. The patient or patient’s legally authorized representative (LAR) must sign and date the
    Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved
    Informed Consent Form (ICF)/Health Insurance Portability and Accountability Act
    (HIPAA) Authorization (if required) prior to study participation. If appropriate, the
    patient will sign an Assent Form.
    2. Male or female patients between 2 and 60 years of age (inclusive).
    3. Patient must have been <11 years of age at the onset of LGS.
    4. Patient must weigh &#8805;12.5 kg.
    5. If female:
    a. Patient is either not of childbearing potential, defined as premenarchal,
    postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation,
    bilateral oophorectomy or hysterectomy), or if of childbearing potential, must
    comply with a method of birth control acceptable to the investigator during the
    study, for at least 30 days prior to randomization and for 30 days following
    completion of the study.
    b. Patient is not breastfeeding.
    c. Patients of childbearing potential must have a negative serum pregnancy test at
    screening and a negative urine pregnancy test performed on Study Day -1.
    6. Patients with LGS as evidenced by:
    a. Greater than 1 type of generalized seizures, including drop seizures (atonic, tonic or
    myoclonic) for at least 6 months.
    b. Written documentation of having met the electroencephalogram (EEG) diagnostic
    criteria for a diagnosis of LGS at some point in their history (must have abnormal
    background activity accompanied by slow spike and wave pattern <2.5 Hz).
    7. Patient must have experienced &#8805;2 drop seizures per week during the 4-week baseline
    period.
    8. Patient must be on at least 1 AED. Patient must be on a stable AED dosing regimen for
    at least 30 days prior to screening. Neither a Vagal Nerve Stimulator (VNS) nor the
    ketogenic diet will count as an AED.
    9. Patients must not have been on any benzodiazepines chronically (for any indication) for
    a period of at least 30 days prior to screening. Patients will be allowed to enter the study
    if they have used benzodiazepines as a rescue therapy within the 30 days prior to
    screening with a limit of 1 rescue per day up to an average of once per week.
    10. In the investigator’s opinion, parent or caregiver must be able to keep an accurate
    seizure diary.
    11. In the investigator’s and parent/caregiver’s opinions, the patient is able to take study
    drug.
    E.4Principal exclusion criteria
    1. Etiology of patient’s seizures is a progressive neurologic disease. Patients with tuberous
    sclerosis will not be excluded from study participation, unless there is a progressive
    tumor.
    2. Patient has had an episode of status epilepticus within 12 weeks of baseline.
    3. Patient has had an anoxic episode requiring resuscitation within 6 months of screening.
    4. Patient has a clinically significant history of an allergic reaction or significant sensitivity
    to benzodiazepines or to any of the other ingredients in clobazam tablets.
    5. Patient is taking more than 3 concurrent AEDs. NOTE: VNS or ketogenic diet is
    allowed and will not be counted in the three allowed AEDs.
    6. Patient has been on the ketogenic diet for less than 30 days prior to screening or suffers
    from frequent stooling.
    7. If the patient has a VNS, the settings have not been stable for at least 30 days prior to
    screening.
    8. Patient has previously been treated with CLB.
    9. Patient has taken corticotropins in the 6 months prior to screening.
    10. Patient is currently taking long-term systemic steroids (excluding inhaled medication for
    asthma treatment) or any other daily medication known to exacerbate epilepsy. An
    exception will be made of prophylactic medication, for example, for idiopathic nephrotic
    syndrome or asthma.
    11. If the patient is taking felbamate, he/she has been taking it for less than 1 year prior to
    screening.
    12. Patient has experienced a clinically significant unresolved idiosyncratic reaction to an
    AED, e.g., topiramate with resulting metabolic acidosis, felbamate with resulting
    aplastic anemia or hepatic failure, or lamotrigine with resulting skin irritation and/or
    rash.
    13. Patient has shown any clinically significant history of hyper-sensitivity to central
    nervous system (CNS)-active medications leading to neurobehavioral aberrations (e.g.,
    increased biting, scratching, kicking or hitting).
    14. If the patient is on any chronic medication, the dose has not been stable for at least 30
    days prior to screening.
    15. Patient has taken or used any investigational drug or device in the 30 days prior to
    screening.
    16. Patient has a clinically significant unstable hepatic, hematological, renal, cardiovascular,
    gastrointestinal, or pulmonary disease or ongoing malignancy.
    17. Patient has a diagnosis of sleep apnea.
    18. Patient has compromised respiratory function or severe respiratory insufficiency.
    19. Patient has a clinically significant abnormal laboratory value.
    20. Patient has familial long QT syndrome, QT/QTc >500msec or a history of polymorphic
    ventricular tachycardia.
    21. Patient has a progressive CNS lesion confirmed by magnetic resonance imaging (MRI)
    or computed tomography (CT) scan.
    22. Patient has a history of drug or alcohol abuse.
    23. Patient has a history of poor compliance on past antiepileptic therapy.
    24. Patient has inadequate supervision by parent or guardian.
    25. For any reason, the patient is considered by the investigator to be an unsuitable
    candidate for the study.
    26. Patient has a history of severe muscle weakness, including myasthenia gravis.
    E.5 End points
    E.5.1Primary end point(s)
    Percent reduction in number of drop seizures (average per week) from the 4-week
    baseline period compared to the 12-week maintenance period.
    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 Yes
    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 Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    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 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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA15
    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
    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
    Planned number of patients:
    To be enrolled worldwide (enter baseline period): Approx. 240
    To be randomized: Approx. 216
    Patients completed [modifiedintent-to-treat (MITT) population]: Approx. 184

    The IDMC will advise the Sponsor (Ovation) on whether to continue, modify or discontinue the study. If, in the judgment of the Sponsor, the continued exposure to the investigational product represents a significant risk to patients, the study will be stopped and the sites will be notified.
    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 months6
    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 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 Yes
    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) Yes
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    The patient or patient's legally authorized representative (LAR) must sign and date the Informed Consent Form (ICF)prior to study participation. If appropriate, the patient will sign an Assent Form
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 240
    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)
    Upon completion of the maintenance period, patients will either discontinue investigational product in a 2 or 3-week taper period or patients will immediately rollover into an open-label extension study, Protocol Code OV-1004 EudraCT number 2007-004350-82).
    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 Decision2008-10-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-10-16
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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