Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2014-003651-54
    Sponsor's Protocol Code Number:2014RISP1
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-10-12
    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 number2014-003651-54
    A.3Full title of the trial
    ‘Off-label use of Risperidone in Children and Adolescents (ORCA): a double-blind placebo-controlled discontinuation trial’
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Off-label risperidone in children and adolescents (ORCA): Discontinuation study
    Off-label risperidon bij kinderen en adolescenten (ORKA): afbouw studie
    A.3.2Name or abbreviated title of the trial where available
    Discontinuation of risperidone in children and adolescents
    A.4.1Sponsor's protocol code number2014RISP1
    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 SponsorUMCG
    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 supportZonMW
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUMCG
    B.5.2Functional name of contact pointRisperidone trial information
    B.5.3 Address:
    B.5.3.1Street AddressPostbus 30.001
    B.5.3.2Town/ cityGroningen
    B.5.3.3Post code9700 RB
    B.5.3.4CountryNetherlands
    B.5.4Telephone number00310503610687
    B.5.6E-mailm.dinnissen@umcg.nl
    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 namerisperidone
    D.3.4Pharmaceutical form Oral solution
    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.3.9.3Other descriptive nameRISPERIDONE
    D.3.9.4EV Substance CodeSUB10335MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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 placeboOral solution
    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
    no specific condition, we will investigate children who have been using risperidone on an off-label basis for at least one year.
    E.1.1.1Medical condition in easily understood language
    no specific condition, we will investigate children who have been using risperidone on an off-label basis for at least one year.
    E.1.1.2Therapeutic area Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To investigate the behavioral effects of controlled discontinuation as well as the feasibility of discontinuing currently ongoing treatment with risperidone in children and adolescents with behavioral problems who have used risperidone for at least one year. Here, we will be able to establish whether or not long-term use of risperidone is still effective beyond one year of treatment. We will also be able to study physical health correlates after discontinuation.
    E.2.2Secondary objectives of the trial
    (1) to investigate the effects of discontinuation of risperidone on a number of secondary outcome variables (problem behavior and comorbidity, clinical improvement, general functioning and quality of life, parental and family functioning, and neuropsychological functioning) and tolerability ratings (side effects and withdrawal effects, physical measures, and blood counts).
    (2) to identify moderators and predictors of treatment discontinuation and long-term outcome six months later. This includes treatment duration and compliance, child factors (age, sex, presence of comorbid psychiatric problems, temperamental traits, biologic factors and genetic factors) as well as parent factors (socio-economic status, parental and family factors).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    In order to be eligible to participate in this study, a subject must meet all of the following criteria:
    • Be between the ages of six and seventeen years and eight months
    • Current risperidone use ≥ one year.
    • Current risperidone doses ≤ 5 mg/day.
    • IQ > 70 (based on a previous IQ test or attending regular education).
    • Parents (or the legal guardian) and children (≥ twelve years) have provided informed consent to participate in the study.
    E.4Principal exclusion criteria
    A potential subject who meets any of the following criteria will be excluded from participation in this study:
    • Risperidone was discontinued for ≥ two months in the last year.
    • Current psychosis.
    • Pregnancy.
    • Risperidone is primarily used for the treatment of psychosis, or tics.
    • Having parents who are planning to start other psychosocial and pharmacological therapies during the blinded period.
    • Having parents who are unable to understand or comply with the protocol.
    • Presence of any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the results of the study, or the participant’s ability to participate in the study.
    E.5 End points
    E.5.1Primary end point(s)
    Problem behavior will be assessed by the Nisonger Child Behavior Rating Form-Typical IQ (NCBRF-TIQ; Aman et al, 2008). This 64-item, parent-reported scale contains a Positive Social subscale (10 items) and six Problem Behavior subscales (54 items): (1) Conduct Problems, (2) Oppositional, (3) Hyperactive, (4) Inattentive, (5) Withdrawn/Dysphoric, and (6) Overly Sensitive. A total Disruptive Behavior Disorder score (D-total) and a total ADHD score (ADHD-total) can be calculated. The primary study parameter will be the D-total, which is calculated by adding the scores on the Conduct problems and the Oppositional behavior scale.
    E.5.1.1Timepoint(s) of evaluation of this end point
    at baseline, eight weeks, fourteen weeks and after six months naturalistic follow up
    E.5.2Secondary end point(s)
    Secondary outcome measures:
    - Strength and Difficulties Questionnaire (SDQ)
    - Retrospective Modified Overt Aggression Scale (R-MOAS)
    - Conner's Teacher Rating Scale-Revised: short form (CTRS-R:S)
    - Clinical Global Impression Scale (CGI)
    - Children's Global Assessment Scale (CGAS)
    - Kindl-R (quality of life)
    - Parental Frustration Questionnaire (PFQ)
    - Amsterdam Neuropsychological Tasks (ANT)
    - UKU side effect rating scale (UKU-SERS)
    - Abnormal Involuntary Movement Scale (AIMS)
    - Barnes Akathisia Scale (BARS)
    - Unified Parkinson's disease rating scale (UPDRS)
    - Sleep Disturbances Scale for Children (SDSC)
    - appetite and life style
    - Physical Activity Questionnaire (PAQ)
    - Physical measures: length, weight, waist circumference, heart rate and blood pressure
    - Blood counts
    •Metabolism: fasting glucose, insulin, triglycerides, high-density lipoproteins (HDL), low-density lipoproteins (LDL), leptine, and total cholesterol.
    •Endocrine parameters: prolactin, testosterone, and estradiol.
    •Bone turnover: P1NP, CTx, osteocalcine, vitamin D, and calcium.
    •Thyroid function: TSH, T4, and parathyreoid hormone.
    •Kidney function: creatinine, sodium, and potassium.
    •Pharmacokinetics: risperidone and 9-hydroxyrisperidone concentrations.
    •Albumine levels.

    Predictor variables:
    - Demographic data and socio-economic status
    - Treatment history and psychiatric diagnosis
    - Tanner stages of pubertal development
    - genetic polymorphisms (e.g. CYP2D6, CYP3A)
    - Nijmeegse Ouderlijke Stress Index-kort (NOSI-K)
    - Alabama Parenting Questionnaire (APQ)
    - Parent-rating scale for Reactive and Proactive Aggression (PRPA)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary outcome measures will be measured at at baseline, eight weeks, fourteen weeks and after six months naturalistic follow up. Predictor variables will be measured at baseline.
    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 Yes
    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 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 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 concerned4
    E.8.5The trial involves multiple Member States No
    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 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
    The end of the study is defined as the last subject last visit. The study will be terminated prematurely when in line with the revised CCMO Directive on the Assessment of Clinical Trial Agreements.
    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 months9
    E.8.9.1In the Member State concerned days0
    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: 120
    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: 120
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 120
    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 No
    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
    children under the age of twelve
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state120
    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)
    none
    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 Decision2015-10-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-10-14
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 06:09:19 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA