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    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   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:2012-003921-13
    Sponsor's Protocol Code Number:12/0368
    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:2013-05-13
    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 number2012-003921-13
    A.3Full title of the trial
    COMbination therapy for PulmonAry hypertension using RacEcadotril (COMPARE).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Racecadotril used in combination with sildenafil to reduce blood pressure in the lungs.
    A.3.2Name or abbreviated title of the trial where available
    Combination therapy in pulmonary hypertension
    A.4.1Sponsor's protocol code number12/0368
    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 College London
    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 supportBritish Heart Foundation
    B.4.2CountryUnited Kingdom
    B.4.1Name of organisation providing supportUCLH/UCL Biomedical Research Centre and UCLH/UCL Clinical Research Development Committee
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity College London
    B.5.2Functional name of contact pointUCL Clinical Trials Unit
    B.5.3 Address:
    B.5.3.1Street AddressClinical Trials Unit, UCL, Gower Street
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeWC1E 6BT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02031083266
    B.5.6E-mailcomparetrial@ucl.ac.uk
    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 Tiorfan
    D.2.1.1.2Name of the Marketing Authorisation holderBioproject Europe Ltd
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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 nameRacecadotril
    D.3.4Pharmaceutical form Capsule
    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 INNRacecadotril
    D.3.9.1CAS number 81110-73-8
    D.3.9.3Other descriptive nameTiorfan 100 mg, capsule
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 placeboCapsule
    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
    Pulmonary hypertension
    E.1.1.1Medical condition in easily understood language
    An increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature.
    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 10037400
    E.1.2Term Pulmonary hypertension
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    There is one main aim: 1. To confirm that when racecadotril is administered to patients with pulmonary hypertension taking sildenafil, it inhibits the enzyme, neutral endopeptidase.
    E.2.2Secondary objectives of the trial
    There are three main secondary aims: 1. To measure the effect of racecadotril, when administered to patients taking sildenafil, on blood pressure, including the blood pressure of the lungs (pulmonary artery pressure). 2. To measure the effect of racecadotril, when administered to patients taking sildenafil,on related blood biomarkers. 3. To assess the safety of racecadotril when administered to patients taking sildenafil.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. WHO Group I pulmonary hypertension(i.e. idiopathic, familial or associated with connective tissue diseases) 2. 18-80 years old 3. Technically satisfactory right heart catheterisation (Step 1 only) 4. On sildenafil (20-100 mg; t.i.d.) 5. Six minute walk distance of equal to or >150 m at entry 6. No changes to PH specific therapies for 1 month 7. Not pregnant (women only). Women of childbearing potential only: Women must have a negative pregnancy test within seven days prior to being registered for trial treatment on day 0; they must be willing to use an effective method of contraception (including hormonal or barrier method of birth control) from the time consent is signed until six weeks after treatment discontinuation 8. Able to provide consent for the trial
    E.4Principal exclusion criteria
    1. Known sensitivity to racecadotril 2. Clinical diagnosis of liver cirrhosis or ALT/AST >two times the upper limit of normal 3. Kidney disease with an eGFR of <50 ml/min 4. History of angioedema 5. Systolic blood pressure <85 mmHg 6. Known history of drug or alcohol abuse within six months of enrolment 7. Participation in a clinical study involving another investigational drug 8. Women who are breastfeeding 9. Any clinical condition for which the investigator would consider the patient unsuitable for the trial.
    E.5 End points
    E.5.1Primary end point(s)
    Maximum percentage change from baseline in plasma atrial natriuretic peptide (ANP) concentration (nM).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Step 1: Blood samples taken at 0,1,2,3 and 6 hours (+/- 15 minutes/time point). Step 2: Blood samples taken on day 0 and on the 12th, or 13th, or 14th day of treatment.
    E.5.2Secondary end point(s)
    Step 1 In patients with PH to determine the effect of a single dose of racecadotril or placebo (either 100 mg or 200 mg p.o). Racecadotril or placebo will be co-administered concurrently with sildenafil (20-100 mg; p.o.). 1. Pulmonary haemodynamic assessments: Maximum change in: 1. Pulmonary vascular resistance (dynes. sec/cm-5) 2. Stroke volume (ml) 3. Pulmonary artery occlusion pressure (mmHg) 4. Arterial saturation (%) 5. Mean arterial pressure (mmHg) 2. Systemic haemodynamic assessments: 1. Systolic and diastolic blood pressure (mmHg) and Heart Rate (BPM) 3. Additional biomarkers in the blood: Brain-type Natriuretic Peptide (BNP)(nM), N-terminal pro brain-type natriuretic peptide (NT-proBNP) (nM), C-type natriuretic peptide (CNP) (pM),Cyclic guanosine-3’,5’-monophosphate (cGMP) (nM), endothelin 1(ET-1) (nM), Nitrite and Nitrate (NOx) (nM) 4. Safety assessment: Adverse events Step 2 In patients with PH, to determine the effects of racecadotril or placebo administered in repeat dosing (100 or 200 mg t.i.d.) concurrently with sildenafil (20-100 mg; p.o.; t.i.d.) for 12, or 13, or 14 days, on; 1. Systemic haemodynamic assessments: Systolic and diastolic blood pressure (mmHg) and heart rate (BPM) 2. Additional biomarkers in the blood: Brain-type Natriuretic Peptide (BNP)(nM), N-terminal pro brain-type natriuretic peptide (NT-proBNP) (nM), C-type natriuretic peptide (CNP) (pM), Cyclic guanosine-3’,5’-monophosphate (cGMP) (nM) , endothelin 1(ET-1) (nM), Nitrite and Nitrate (NOx) (nM) 3. Safety assessment: Adverse events 4. Six minute walk test (m)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Step 1: Pulmonary haemodynamics measured at 0, 1.5 and 2 hours (+/- 10 minutes /time point) Systemic haemodynamics measured at 0 and then every 30 minutes up to 6 hours (+/- 15 minutes /time point) Blood samples taken at 0,1,2,3 and 6 hours (+/- 15 minutes /time point). Step 2: Blood samples taken on day 0 and on the 12th, or 13th, or 14th day of treatment. Systemic haemodynamics measured on day 0 and on the 12th, or 13th, or 14th day of treatment. Six minute walk test measured on day 0 and on the 12th, or 13th, or 14th day of treatment.
    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 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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    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 as being upon 30 days after the completion of all clinical data entry of the data received at the UCL CTU and the resolution of all clinical data queries.
    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 days0
    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 No
    F.1.1Number of subjects for this age range: 0
    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) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 18
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 6
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state24
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 0
    F.4.2.2In the whole clinical trial 0
    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)
    There can be no guarantee that the drugs used in the study will be made available to the patients at the end of the trial, this will depend on funding resources within the Trust or the Primary Care Trust (PCT) and other local priorities. The patients will continue to be treated in accordance with standard NHS practice.
    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 Decision2013-05-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-06-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-04-05
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