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    Summary
    EudraCT Number:2009-013165-25
    Sponsor's Protocol Code Number:TAK-491_109
    Clinical Trial Type:Outside EU/EEA
    Date on which this record was first entered in the EudraCT database:2013-05-07
    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
    H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED
    Expand All   Collapse All
    A. Protocol Information
    A.2EudraCT number2009-013165-25
    A.3Full title of the trial
    A Comparative Single-Dose Pharmacokinetic and Safety Study of TAK-491 Between
    Infants, Children, and Adolescents with Hypertension and Healthy Adults
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A research project to find out how safe and effective a single dose of TAK-491 research medicine is, after it has been taken by children aged 6 months – 16 years who have high blood pressure. Healthy adults will also be included in this research project to provide a comparison.
    A.4.1Sponsor's protocol code numberTAK-491_109
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01078376
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/39/2011
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorTakeda Global Research & Development Centre (Europe) Ltd.
    B.1.3.4CountryUnited Kingdom
    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 supportTakeda Global Research & Development Centre (Europe)
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationTakeda Global Research & Development Centre (Europe) Ltd.
    B.5.2Functional name of contact pointClinical Study Manager
    B.5.3 Address:
    B.5.3.1Street Address61 Aldwych
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeWC2B 4AE
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+440203 116 8000
    B.5.5Fax number+440203 116 8199
    B.5.6E-mailclinicaloperations@tgrd.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 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 nameazilsartan medoxomil
    D.3.2Product code TAK-491
    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 INNazilsartan medoxomil
    D.3.9.1CAS number 863031-24-7
    D.3.9.2Current sponsor codeTAK-491
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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.IMP: 2
    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 nameazilsartan medoxomil
    D.3.2Product code TAK-491
    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 INNazilsartan medoxomil
    D.3.9.1CAS number 863031-24-7
    D.3.9.2Current sponsor codeTAK-491
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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.IMP: 3
    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 nameazilsartan medoxomil
    D.3.2Product code TAK-491
    D.3.4Pharmaceutical form Granules for oral suspension
    D.3.4.1Specific paediatric formulation Yes
    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 INNazilsartan medoxomil
    D.3.9.1CAS number 863031-24-7
    D.3.9.2Current sponsor codeTAK-491
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Hypertension
    E.1.1.1Medical condition in easily understood language
    High blood pressure
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10020772
    E.1.2Term Hypertension
    E.1.2System Organ Class 10047065 - Vascular disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10015488
    E.1.2Term Essential hypertension
    E.1.2System Organ Class 10047065 - Vascular 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 objectives of this study are to determine the pharmacokinetic parameters, safety, and tolerability of a single dose of TAK-491 in pediatric subjects with hypertension, who are between the ages of 6 months to 16 years (including those up to their 17th birthday) and gendermatched healthy adult subjects aged 18 to 45 years, inclusive.
    E.2.2Secondary objectives of the trial
    Not applicable
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Main Criteria for Inclusion:
    Pediatric subjects:
    boys or girls must have a diagnosis of hypertension (SBP and / or DBP ≥ 95th percentile for gender / age / height), aged ≥6 months to <17 years, subjects 6 years of age and older must have the ability to swallow a tablet;
    subjects qualifying for Cohorts 1 and 2 must weigh at least 20 kg and up to 100 kg; subjects qualifying for Cohort 3 must weigh at least 6.5kg;
    subjects must have been at a constant weight, or expected weight gain for that particular age, for 30 days with no change to the dose of their diuretic drugs;
    subjects in Cohort 3 may be a renal transplant patient if all other inclusion and none of the exclusion criteria are met, time post-transplant has been > 6 months prior to Check-in (Day-1) with stable graft function (and estimated GFR ≥30mL/min/1.73 m2) for at least 6 months, with no change to medications such as immunosuppressive therapy for at least 60 days prior to Check-in (Day-1), and no evidence of transplant renal artery stenosis or anemia.

    Adult subjects for Cohort 1: must be healthy male or females;
    aged 18 to 45 years, inclusive;
    have diastolic blood pressure (DBP) between 60 and 90 mm Hg, and systolic blood pressure (SBP) between 100 and 140 mm Hg, inclusive at Screening or Check-in (Day-1);
    have a minimum body weight of 50kg, with a body mass index of 18 to 32 kg/m2 (inclusive) at Screening.
    E.4Principal exclusion criteria
    Main Criteria for Exclusion:
    Pediatric subjects:
    current treatment with more than 2 antihypertensive agents;
    sitting trough clinical SBP/DBP exceeding the 99th percentile for age/gender/height by >15/>10 mm Hg;
    the subject has renovascular disease affecting both kidneys or solitary kidney, including dialysis treatment, severe nephrotic syndrome not in remission;
    for Cohorts 1 and 2 only a previous renal transplant.

    All subjects:
    history or clinical manifestations of significant disorders;
    acute, clinically significant illness within 30 days prior to check-in (Day-1); hemodynamically significant left ventricular outflow obstruction due to aortic
    valvular disease, cardiomyopathy, or uncorrected aortic coarctation;
    diagnosis of malignant or accelerated hypertension;
    severe hepatic impairment;
    alanine aminotransferase, aspartate aminotransferase >2 times the upper limit of normal, or total bilirubin >1.5 times the upper limit of normal;
    glycosylated hemoglobin >8.5%;
    hyperkalemia;
    creatinine clearance <30 mL/min/1.73 m2;
    serum albumin <2.5 g/dL;
    intake of potent CYP enzyme inducers or inhibitors or any other prespecified excluded medication, allergy to an angiotensin type II receptor blocker or any of the excipients;
    pregnancy.
    E.5 End points
    E.5.1Primary end point(s)
    Primary Endpoints:
    Primary plasma pharmacokinetic endpoints for TAK-536 and TAK-536 M-II are as follows: area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC[0-tlqc]), area under the plasma concentration-time curve from time 0 to infinity (AUC[0-inf]), maximum observed plasma concentration (Cmax), time to reach Cmax (Tmax), terminal elimination half-life (T1/2), and apparent oral clearance (CL/F) (TAK-536 only, assuming complete conversion from TAK-491 to TAK-536).

    For Cohorts 1 and 2 urine pharmacokinetic endpoints for TAK-536 and TAK-536 M-II are as follows: total amount of drug excreted in urine from time 0 to 24 hours postdose (Ae[0-t]), fraction of unchanged drug excreted in urine from 0 to 24 hours postdose (Fe%), and renal clearance (CLr) from 0 to 24 hours postdose.

    E.5.1.1Timepoint(s) of evaluation of this end point
    For Cohorts 1 and 2, one blood sample (2 mL for all pediatrics and 6 mL for adults in Cohort 1)
    will be obtained at the following designated time points for pharmacokinetic analysis of the
    plasma:
    Day 1: predose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose.
    For Cohort 3, one blood sample (all samples 1 mL except the 0.25 and 1 hour which are 2 mL)
    will be obtained at the following designated time points for pharmacokinetic analysis of the
    plasma:
    Day 1: predose and at 0.25, 1, 6, 12, and 24 hours postdose.
    TAK-536 and TAK-536 M-II will be analyzed in all samples. TAK-491F will be analyzed in all
    predose, 0.25 and 1 hour samples and the 0.5 hour samples of Cohorts 1 and 2.
    E.5.2Secondary end point(s)
    For Cohorts 1 and 2 urine pharmacokinetic endpoints for TAK-536 and TAK-536 M-II are as follows: total amount of drug excreted in urine from time 0 to 24 hours postdose (Ae[0-t]),
    fraction of unchanged drug excreted in urine from 0 to 24 hours postdose (Fe%), and renal clearance (CLr) from 0 to 24 hours postdose.
    E.5.2.1Timepoint(s) of evaluation of this end point
    9.1.13.3 Collection of Urine for Pharmacokinetic Sampling
    For Cohorts 1 and 2 only, urine samples will be obtained, when possible, at the following
    designated time points from subjects for pharmacokinetic analysis of TAK-536 and TAK-536
    M-II in urine:
    Day 1: predose (a single collection between -12 to 0 hours), 0 to 4, 4 to 8, 8 to 12, and 12 to 24 hours postdose.
    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 No
    E.6.6Pharmacokinetic Yes
    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) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Pharmacokinetic
    E.7.2Therapeutic exploratory (Phase II) No
    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 No
    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 Yes
    E.8.1.7.1Other trial design description
    Comparative
    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
    healthy adult subjects who are gender-matched to the pediatric subjects of Cohort 1
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 Will this trial be conducted at a single site globally? No
    E.8.4 Will this trial be conducted at multiple sites globally? Yes
    E.8.6 Trial involving sites outside the EEA
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3Specify the countries outside of the EEA in which trial sites are planned
    United States
    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.8.9.2In 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 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: 24
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 8
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 8
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 8
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 8
    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 Yes
    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
    Peadiatric Subjects.

    See Protcocol sections 15 (ETHICAL ASPECTS OF THE STUDY) and 16 (ETHICAL CONSIDERATIONS FOR PEDIATRIC SUBJECTS) for details of consent/assent.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 32
    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)
    A follow-up phone call to the subjects will be made on study Day 6 (±1 day) and study Day 15 (±1 day) for the assessment of AEs and concomitant medication.
    G. Investigator Networks to be involved in the Trial
    H.4 Third Country in which the Trial was first authorised
    H.4.1Third Country in which the trial was first authorised: United States
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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