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The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
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    The EU Clinical Trials Register currently displays   41198   clinical trials with a EudraCT protocol, of which   6743   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
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    Summary
    EudraCT Number:2014-002387-32
    Sponsor's Protocol Code Number:UoL001019
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-06-27
    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 ConcernedUK - MHRA
    A.2EudraCT number2014-002387-32
    A.3Full title of the trial
    Phase IIa, Randomised, Controlled, Open-Label Trial of Rosuvastatin for the Prevention of Aminoglycoside-Induced Kidney Toxicity in Children with Cystic Fibrosis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Trial of Rosuvastatin for the Prevention of Kidney Toxicity caused by Tobramycin in Children with Cystic Fibrosis
    A.3.2Name or abbreviated title of the trial where available
    PROteKT
    A.4.1Sponsor's protocol code numberUoL001019
    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 of Liverpool
    B.1.3.4CountryUnited Kingdom
    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 supportMedical Research Council
    B.4.2CountryUnited Kingdom
    B.4.1Name of organisation providing supportThe J P Moulton Charitable Foundation
    B.4.2CountryUnited Kingdom
    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 Crestor
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca UK Ltd
    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 nameCrestor
    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 INNRosuvastatin calcium
    D.3.9.1CAS number 287714-41-4
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Aminoglycoside-induced nephrotoxicity
    E.1.1.1Medical condition in easily understood language
    Kidney injury caused by a type of antibiotic called an aminoglycoside
    E.1.1.2Therapeutic area Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10011762
    E.1.2Term Cystic fibrosis
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10069022
    E.1.2Term Kidney injury molecule-1
    E.1.2System Organ Class 10022891 - Investigations
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10067571
    E.1.2Term Nephrotoxicity
    E.1.2System Organ Class 100000004857
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Does rosuvastatin protect against kidney damage caused by aminoglycoside antibiotics?

    This will be assessed by comparing the difference in the change in the urine biomarker KIM-1 from baseline to 'highest concentration' concentration during exposure to tobramycin between the rosuvastatin treated arm and control arm.
    E.2.2Secondary objectives of the trial
    1. Change in serum concentration of creatinine and eGFR during tobramycin exposure between rosuvastatin treated arm and the control arm.
    2. Change in other urinary and plasma biomarkers of renal injury during tobramycin exposure between rosuvastatin treated arm and the control arm.
    3. Difference in serious adverse events between rosuvastatin treated arm and the control arm.
    4. Difference in tobramycin concentrations between rosuvastatin treated arm and the control arm to identify any pharmacokinetic interaction between rosuvastatin and the tobramycin.
    5. Difference in Forced Expiratory Volume in 1 second (FEV1) and C-Reactive Protein, between rosuvastatin treated arm and the control arm to identify any pharmacodynamics interaction between rosuvastatin and the tobramycin
    6. Assessment of plasma rosuvastatin concentrations achieved in children randomised to the intervention arm.
    7. Difference in biomarkers of Pseudomonas aeruginosa between rosuvastatin treated arm and the control
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Title: Molecular genetics of aminoglycoside-induced nephrotoxicity
    Date: 6th June 2014
    Version 1.2

    All children who are invited to participate in the PROteKT study will also be invited to participate in a substudy to assess the molecular genetics of aminoglycoside-induced nephrotoxicity.

    There exists a considerable degree of inter-individual variability in susceptibility to aminoglycoside-induced nephrotoxicity, and the reasons for this are not clear from the available literature. In particular, whether there is any genetic component to this variability has not been investigated previously in a genome-wide approach.

    During this study all participants will be exposed to IV tobramycin as part of their routine clinical care. We will collect a sample for molecular genetic analysis from each child who consents to do so, and identify aminoglycoside-induced nephrotoxicity using novel biomarkers and serum creatinine.

    The samples collected in this study will be combined with:
    1. Samples collected through the MAGIC study (Molecular Genetics of Adverse Drug Reactions in Paediatric Patients), Research Ethics No: 10/H1002/57.
    2. Samples collected through worldwide efforts to evaluate genetic factors predisposing to drug-induced renal injury.

    In the future, we will conduct a genome wide association study (GWAS) to identify genetic risk factors for aminoglycoside-induced nephrotoxicity. Any positive hits will be further investigated using functional approaches to elucidate mechanisms and identify causal variants.

    We will aim to assess the feasibility of carrying out a molecular genetic study in this group of children, and to address the following objectives:
    (1) Identify genetic risk factors for aminoglycoside-induced nephrotoxicity in children with CF in order to provide better preventive strategies in the future.
    (2) Identify causal mechanisms of aminoglycoside-induced AKI by exploring genotype/phenotype correlations, in order to provide better interventional strategies in future.

    E.3Principal inclusion criteria
    1. Age 10 to 18 years inclusive.
    2. Diagnosis of cystic fibrosis (established by sweat test or genotype).
    3. Planned, clinically indicated, course of treatment with IV tobramycin.
    4. Ability to give informed consent.
    5. Willingness to comply with all study requirements.
    6. Able to take tablets.


    E.4Principal exclusion criteria
    1. Existing treatment with a statin.
    2. Previous adverse reaction to a statin.
    3. Co-enrolment in other drug trials*, or completion of a previous CTIMP within the last 30 days
    4. Previous randomisation in the PROteKT trial
    5. Patients taking any of the following medications: Ciclosporin, Protease Inhibitors, Fibrates, Ezetimibe, Erythromycin (but not other macrolides), Eltrombopag, Dronedarone, Itraconazole, Coumarins, Oral contraceptives, nicotinic acid, fusidic acid and Simepravir.
    6. Female participants who are pregnant or lactating (female participants of childbearing potential must use a barrier method of contraception if sexually active whilst taking rosuvastatin and for 7 days afterwards).
    7. Patients of Asian ancestry (Japanese, Chinese, Filipino, Vietnamese, Korean and Indian).
    8. Patients with renal disease (eGFR<60ml/min/1.73m², using the Schwartz formula, in the 6 months preceding randomisation).
    9. Patients with current elevation in transaminases exceeding 3x the upper limit of normal.
    10. Family history, or personal history, of hereditary muscular disorders.
    11. Patients with myopathy.
    12. Patients with a history of, or active alcohol abuse.
    13. Patients with hypothyroidism.
    14. Patients with galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption.
    15. Patients who are Hepatitis C positive or HIV-positive.

    *Patients who are currently taking part in TORPEDO-CF are allowed to take part in PROteKT as long as their date of randomisation into TORPEDO-CF is not within the previous six months of the screening date for PROteKT.



    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome measure is difference in mean fold-change in urinary KIM-1 from baseline to 'highest concentration' concentration during exposure to tobramycin between the rosuvastatin treated arm and control arm.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Urine samples, for measurement of urinary KIM-1, will be collected from each child at baseline, and on each day of aminoglycoside treatment (usually lasting 2 weeks). A further sample will be collected at the 4 week follow-up visit.

    E.5.2Secondary end point(s)
    1. Difference in serum concentration of creatinine and eGFR during tobramycin exposure between rosuvastatin treated arm and the control arm.
    2. Difference in other urinary and plasma biomarkers of renal injury during tobramycin exposure between rosuvastatin treated arm and the control arm.
    3. Difference in serious adverse events between rosuvastatin treated arm and the control arm.
    4. Difference in tobramycin concentrations between rosuvastatin treated arm and the control arm to identify any pharmacokinetic interaction between rosuvastatin and the tobramycin.
    5. Difference in Forced Expiratory Volume in 1 second (FEV1) and C-Reactive Protein, between rosuvastatin treated arm and the control arm to identify any pharmacodynamics interaction between rosuvastatin and the tobramycin
    6. Relationship between plasma rosuvastatin concentrations achieved in children randomised to the intervention arm and change in urinary KIM-1.
    7. Difference in biomarkers of Pseudomonas aeruginosa between rosuvastatin treated arm and the control arm.

    E.5.2.1Timepoint(s) of evaluation of this end point
    Blood samples, for secondary endpoints 1, 2, 4, 5, 6, and 7, will be collected at baseline (T0), T+1 day, T+8 days, T+13 days, and the 4 week follow-up visits.

    Urine samples, for secondary endpoints 2 and 7, will be collected at baseline, on each day of aminoglycoside treatment (usually lasting 2 weeks), and the 4 week follow-up visit.

    FEV1, for secondary endpoint 5, will be measured at baseline (T0), T+8 days, T+13 days, and the 4 week follow-up visits.
    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 No
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 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 Yes
    E.8.2.3.1Comparator description
    No intervention
    E.8.2.4Number of treatment arms in the trial1
    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 concerned12
    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 end of the trial is defined to be the date on which data for all participants has been finalised and all data has been entered onto the database.
    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 months0
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days1
    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: 45
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 10
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 35
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 5
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    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 No
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state50
    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)
    Following the trial, there will be no continuing availability of the investigational medicinal product to participants. They will receive continuation of normal clinical care.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-07-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-08-05
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-12-13
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