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    Summary
    EudraCT Number:2010-021343-41
    Sponsor's Protocol Code Number:ME040
    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:2011-11-30
    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 number2010-021343-41
    A.3Full title of the trial
    Effect of sapropterin on variations of blood phenylalanine and tyrosine over 24 hours and from day to day in children with phenylketonuria
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Variations of blood phenylalanine and tyrosine in children with phenylketonuria under sapropterin
    A.4.1Sponsor's protocol code numberME040
    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 SponsorUniversity Medical Center Groningen
    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 supportMerck KGaA
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Medical Center Groningen
    B.5.2Functional name of contact pointIndependent expert
    B.5.3 Address:
    B.5.3.1Street AddressHanzeplein 1
    B.5.3.2Town/ cityGroningen
    B.5.3.3Post code9713 GZ
    B.5.3.4CountryNetherlands
    B.5.4Telephone number00310503614147
    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 Kuvan
    D.2.1.1.2Name of the Marketing Authorisation holderMerck KGaA
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/04/199
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Soluble tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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
    Phenylketonuria (PKU) is an autosomal recessive metabolic genetic disorder by a mutation in the gene for the enzyme phenylalanine hydroxylase (PAH), rendering it nonfunctional. Left untreated, the disease will result in high concentrations of phenylalanine (Phe) in blood and tissues, likely resulting in severe mental retardation and behavioural problems. Treatment focusus on the restriction of dietary phenylalanine intake with supplementation of a synthetic phenylalaninefree amino acid mixture.
    E.1.1.1Medical condition in easily understood language
    Phenylketonuria (PKU) is an autosomal recessive metabolic genetic disorder. Untreated, PKU can lead to mental retardation and behavioural problems.
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To measure the effect of sapropterin on diurnal and day to day variations of blood phenylalanine concentrations.
    E.2.2Secondary objectives of the trial
    - To measure the effect of sapropterin on diurnal and day to day variations of blood tyrosine concentrations.
    - To measure the effect of sapropterin on diurnal and day to day variations of blood phenylalanine/tyrosine ratios.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Males and females 4-12 years of age.
    - Diagnosed with phenylketonuria by newborn screening.
    - Tested to be sapropterin responsive.
    - Under good metabolic control; defined as 2/3 or 67% of the blood phenylalanine levels within target ranges during the last year.
    E.4Principal exclusion criteria
    - Concomitant disease which may preclude the participation in the study in the judgment of the investigator.
    - Intercurrent illness which might influence the blood phenylalanine levels.
    - Concomitant medication as mentioned in the Kuvan® SPC.
    - Known hypersensitivity to Kuvan® or its excipients.
    - Known hypersensitivity to other approved or non-approved formulations of tetrahydrobiopterin.
    - Non-compliance with study procedures in the judgement of the investigator.
    E.5 End points
    E.5.1Primary end point(s)
    The mean standard deviations of the blood phenylalanine concentrations measured four times a day of 2 consecutive days and once a day on 8 consecutive days of all participants compared between the sapropterin + diet treatment period and the diet alone treatment period.
    E.5.1.1Timepoint(s) of evaluation of this end point
    In both study periods blood sampling is scheduled for the first six days once a day (7-8 am) and four times daily (7-8 am, 12-1 pm, 5-6 pm and bedtime) on the two days thereafter, in total 28 samples per patient.
    E.5.2Secondary end point(s)
    - The mean standard deviations of the blood tyrosine concentrations measured once a day on 8 consecutive days of all participants compared between the sapropterin + diet treatment period and the diet alone treatment period.
    - The mean standard deviations of the blood tyrosine concentrations measured four times a day of 2 consecutive days of all participants compared between the sapropterin + diet treatment period and the diet alone treatment period.
    - The mean standard deviations of the blood phenylalanine/tyrosine ratios measured once a day on 8 consecutive days of all participants compared between the sapropterin + diet treatment period and the diet alone treatment period.
    - The mean standard deviations of the blood phenylalanine/tyrosine concentrations measured four times a day of 2 consecutive days of all participants compared between the sapropterin + diet treatment period and the diet alone treatment period.
    E.5.2.1Timepoint(s) of evaluation of this end point
    In both study periods blood sampling is scheduled for the first six days once a day (7-8 am) and four times daily (7-8 am, 12-1 pm, 5-6 pm and bedtime) on the two days thereafter, in total 28 samples per 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 No
    E.6.5Efficacy No
    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 No
    E.8.1.1Randomised Yes
    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 Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    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 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
    The sponsor will notify the accredited METc and the competent authority of the end of the study within a period of 90 days. The end of the study is defined as the last patient finishes the second blood phenylalanine and tyrosine 8 days measuring period.
    In case the study is ended prematurely, the sponsor will notify the accredited METc and the competent authority within 15 days, including the reasons for the premature termination.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    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: 20
    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: 20
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 20
    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
    Patients from age 4 to 12 incl.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    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 continue their standard treatment regime after participation in the study.
    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 Decision2014-03-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-03-05
    P. End of Trial
    P.End of Trial StatusOngoing
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