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    The EU Clinical Trials Register currently displays   43862   clinical trials with a EudraCT protocol, of which   7285   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2010-021884-34
    Sponsor's Protocol Code Number:PERS3
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-04-17
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2010-021884-34
    A.3Full title of the trial
    Relapse prevention in children and adolescents with DSM-IV Conduct Disorder treated with Risperidone: a Randomized Double blind, Placebo-Controlled, Discontinuation Study.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Relapse prevention in children and adolescents with aggressive anti-social behavior treated with risperidone: a randomized double blind, placebo-controlled, discontinuation study.
    A.3.2Name or abbreviated title of the trial where available
    CONCA-2
    A.4.1Sponsor's protocol code numberPERS3
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorRadboud University Medical Centre Nijmegen
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportRadboud University Medical Centre Nijmegen
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationRadboud University Medical Centre Nijmegen
    B.5.2Functional name of contact pointClinical Trial Information
    B.5.3 Address:
    B.5.3.1Street AddressReinier Postlaan 12
    B.5.3.2Town/ cityNijmegen
    B.5.3.3Post code6525 GC
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+310243512222
    B.5.5Fax number+31 0243512211
    B.5.6E-mailpersproject@karakter.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 Risperidone
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen Cilag
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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 nameRisperidone
    D.3.2Product code 6000803
    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 INNRisperidone
    D.3.9.1CAS number 106266-06-2
    D.3.9.2Current sponsor codeCHMP/384877/2008
    D.3.9.3Other descriptive nameRISPERIDONE
    D.3.9.4EV Substance CodeSUB10335MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number0.25 to 3.0
    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
    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
    Conduct Disorder DSM-IV-TR; 312.8x, APA 2000
    E.1.1.1Medical condition in easily understood language
    Aggressive antisocial behaviour
    E.1.1.2Therapeutic area Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10064478
    E.1.2Term Conduct disorder
    E.1.2System Organ Class 10037175 - Psychiatric 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 objective is to test the hypothesis that, after at least 16 weeks of daily administration (4 for titration, 12 of relatively stable dose, 4 of which at fixed doses, (Study Period 1), risperidone given orally in a dose of 0.25 – 3.0 mg/d depending on body weight (eq. to approximately 0.01 – 0.04 mg/kg/d) is superior to placebo in preventing relapse of symptoms of CD, as assessed through a 12 week, double-blind discontinuation trial (Study Period 2) of children and adolescents not developmentally delayed/mentally retarded, and measured by comparison with mean change from the double-blind baseline to endpoint on the Nisonger Child Behavior Rating Form (CBRF) - Typical IQ Version-ODD/CD disruptive behavior (DBD) Composite Total score (Aman et al., 2008) using investigator-ratings based on all available information.

    E.2.2Secondary objectives of the trial
    To establish the long-term efficacy of treatment with risperidone, measuring mean change from the double-blind baseline to endpoint on the pivotal (Nisonger) scale between risperidone and placebo.
    To test the effect of risperidone compared to placebo on various behavioural domains following seven months of daily administration of risperidone assessed in a 12‐week, double‐blind discontinuation trial.
    To compare changes (impairment) in neurocognitive function following risperidone, assessed in both the 16 weeks open label and the 12-week, double-blind discontinuation trial.
    To assess the effect of risperidone compared to placebo on comorbid ADHD symptoms following seven months of daily administration of risperidone assessed in a 12-week, double-blind discontinuation trial.
    To compare safety and tolerability results for risperidone and placebo in children and adolescents with CD over 12 weeks of double-blind treatment.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    A Randomized Double-Blind, Placebo-Controlled Study of Risperidone in the Treatment of DSM-IV-TR Conduct Disorder in Children and Adolescents.

    Date 01-04-2012

    The primary objective of this study is to test the hypothesis that risperidone given orally in a dose of 0.25 – 3.0 mg/d depending on body weight (eq. to approximately 0.01 – 0.04 mg/kg/d) for 12 weeks is superior to placebo in reducing disruptive behavioural symptoms associated with DSM-IV-TR defined Conduct Disorder (CD) in the treatment of in- and outpatient children and adolescents (5;0 - < 17;9 y.) not developmentally delayed/mentally retarded, as measured by last-observation-carried-forward (LOCF) mean change from baseline to endpoint on the pivotal scale, the Nisonger Child Behavior Rating Form (CBRF) - Typical IQ Version-ODD/CD disruptive behavior (DBD) Composite Total score (Aman et al., 2008) using investigator-ratings based on all available information.
    E.3Principal inclusion criteria
    Patients are eligible to be included in the study only if they meet all of the inclusion criteria below.
    [1] Patients (male or female) must be at least 5 years of age, and not more than 17 years and 5 months of age at Visit 1.
    [2] Patients must meet DSM-IV-TR diagnostic criteria for DSM-IV CD (312.xx) as confirmed by the Kiddie-SADS, Conduct Disorder Module (Kaufman et al., 1996).
    [3] Patients must have an IQ of > 85, measured by 4 subtests (2 verbal plus 2 performance tests) from the Wechsler IQ Scales, (e.g. WISC; WAIS; assessed within < 2 y. before or at study entry), e.g. vocabulary, similarities, block design, and matrix reasoning (cf. Crawford et al., 2010). Age- and country-specific adaptations may be used (detailed instructions may be provided in a respective extra document)
    [4] Patients must score ≥ 27 on the Nisonger CBR Form, ODD/CD Disruptive Behavior Composite (D-Total) at baseline (Visit 1 or 2).
    [5] Patients must score ≥ 4 (“moderately ill” or “markedly ill”) on the CGI-S rating scale at both baseline measures (visit 1 and 2).
    [6] Patients must have a body weight comprised between 5th and 95th percentile based on WHO Body Mass Index for age-sex specific charts, at study entry.
    [7] Patients must be able to swallow the study drug.
    [8] Patients must have venous access sufficient to allow blood sampling and are compliant with blood draws as per protocol.
    [9] If the patient is a female with child-bearing potential, she must test negative for pregnancy (based on a urine pregnancy test) at the time of enrollment and agree to use a reliable method of birth control. Adequate contraception includes: oral contraceptives, intraueterine devices; double barrier method (diaphragm or condom plus spermicide, Norplant™ or Depot Provera™).
    [10] Laboratory results, including serum chemistries, hematology and urinalysis, show no significant abnormalities (significant would include laboratory deviations requiring acute medical intervention or further medical evaluation) and there is no clinical information that, in the judgment of a physician, should preclude a patient’s participation at study entry.
    [11] All patients must have an ECG at Visit 1 or 2. Results must be available prior to dispensing drug at Visit 3. If an ECG shows any severe abnormality, the patient must be excluded from the study. Patients with other abnormalities may be included at the discretion of the investigator.
    [12] Educational level and degree of understanding so that the patients and parents (or legal representative) can communicate suitably with the investigator and study coordinator.
    [13] Subjects’ parents/legal guardians must provide and sign informed consent documents; patients must provide informed consent, and sign consent or assent documents if capable, according to the legal requirements in the very country. A reliable person (primary caregiver, parent) must be available to ensure compliance with study procedures throughout the course of the study.
    [14] Patients meeting criteria for comorbid ADHD (as to the clinical judgement of the investigator) will not be excluded from study participation.
    E.4Principal exclusion criteria
    A patient will be excluded from the study if he or she meets any exclusion criterion described below.
    [1] An immediate family member of the patient is professionally affiliated to the investigator site. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
    [2] Has previously completed or withdrawn from this study or has been previously identified as being a non-responder or intolerant of risperidone.
    [3] Has been treated within 14 days before Visit 1 with a drug that has not received regulatory approval for any indication at the time of study entry, or has participated in any investigational drug trial within six months prior to baseline (visit 1).
    [4] Has a current (within 6 months of the start of the study) or lifetime DSM-IV diagnosis of schizophrenia-related disorders, schizophrenia, bipolar disorder, major depressive disorder or a current substance dependence disorder (given the nature of the study population substance misuse or abuse is not exlusionary), pervasive developmental disorder (autistic disorder or Asperger disorder).
    [5] In the clinical judgment of the investigator, currently meets criteria for a primary psychiatric disorder, e.g., Anxiety Disorder, Depressive Disorder, Tic Disorder or Tourette’s Syndrome (comorbid ADHD is permitted, cf. Incl. criteria section).
    [6] Starts any psychotropic medication, including health-food supplements that the investigator feels could have central nervous system activity (for example, St. John’s Wort, melatonin), during the course of the study, or is taking any other excluded concomitant medication(s) specified in Section 5.7). (An ongoing long-term medication, e.g., to treat a comorbid disorder such as ADHD, is permitted as long as compound and dose are not changed throughout the course of the study).
    [7] Has a history of hypersensitivity to neuroleptics, of tardive dyskinesia, or neuroleptic malignant syndrome.
    [8] Has any acute or unstable medical condition, physiological condition, clinically significant laboratory, or ECG results that, in the opinion of the investigator, would compromise participation in the study.
    [9] Has a known or suspected seizure disorder.
    [10] Female patients who are pregnant or breastfeeding.
    [11] Patients with a history of severe allergies to more than 1 class of medications or multiple adverse drug reactions.
    E.5 End points
    E.5.1Primary end point(s)
    Clinical response is defined as > 25 % reduction from baseline score on the Nisonger CBRF-TIQ D-Total subscale at endpoint (based on a personal communication of the scale author, Dr. Michael Aman, June 2010) and a score of 1 or 2 (“much” or very much” improved) on the CGI-Improvement scale.

    The primary efficacy measure will be comparison of the number of days from randomization to relapse for each treatment group using the Kaplan-Meier product limit estimator. Relapse is defined as a deterioration of > 2 points on the CGI-Severity scale and a 25% increase in the score on the Nisonger CBRF-TIQ D-Total compared to start of Study Period II (average of Visits 7 an 8), for at least two consecutive visits, 6–8 days apart (Reyes et al., 2006).

    The Clinical Global Impressions-Severity (CGI-S) is a single-item rating of the clinician’s assessment of the severity of symptoms in relation to the clinician’s total experience with CD patients (Guy, 1976; NIMH, 1985). Severity is rated on a 7-point scale (1 = normal, not at all ill; 7 = among the most extremely ill subjects).
    Relapse is defined also as a CGI-S worsening of > than 2 points.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Within four years after start of inclusion first patient
    E.5.2Secondary end point(s)
    The secondary outcome measures focus on assessment of changes with active treatment vs. placebo.

    - CGI-I and CGI-S (Guy, 1976; NIMH, 1985)
    - C-GAS (Kaufman, 1996)
    - ADHD-DSM IV-RS (DuPaul et al., 1998)
    - OAS-M (Coccaro et al., 1991)
    - CHIP-CE (Riley et al.2004)
    - Child Behavior Checklist (CBCL), parent-reported (Achenbach, 1991a)
    - PAERS (March et al., 2007)
    - ANT (De Sonneville, 1999)
    - C-SSRS (Posner et al., 2007b)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Within four years after start of inclusion first patient
    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 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) No
    E.7.4Therapeutic use (Phase IV) Yes
    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.8.2.4Number 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA13
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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 years0
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days7
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months7
    E.8.9.2In all countries concerned by the trial days7
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 22
    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.1.1.5.1Number of subjects for this age range: 11
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 11
    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
    Since the subjects in this trial are also children, the consent of a legally authorized representative (or representative) must be sought.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state22
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 200
    F.4.2.2In the whole clinical trial 200
    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)
    Provided in the protocol
    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 Decision2012-04-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-01-24
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2013-01-01
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