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    The EU Clinical Trials Register currently displays   40651   clinical trials with a EudraCT protocol, of which   6635   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2015-005448-32
    Sponsor's Protocol Code Number:DIUR-006
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2016-07-05
    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 ConcernedUK - MHRA
    A.2EudraCT number2015-005448-32
    A.3Full title of the trial
    A Phase III extension study of efficacy, safety and tolerability of Chronocort® in the treatment of congenital adrenal hyperplasia (CAH)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The proposed study aims to build on the results of clinical studies DIUR-003 and DIUR-005 and evaluate the long-term safety of Chronocort® and also its long term efficacy.
    A.4.1Sponsor's protocol code numberDIUR-006
    A.5.4Other Identifiers
    Name:IND No. Number:76485
    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 SponsorDiurnal 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 supportDiurnal Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDiurnal Ltd
    B.5.2Functional name of contact pointClinical Trials Information
    B.5.3 Address:
    B.5.3.1Street AddressCardiff Medicentre, Heath Park
    B.5.3.2Town/ cityCardiff
    B.5.3.3Post codeCF14 4UJ
    B.5.3.4CountryUnited Kingdom
    B.5.6E-mailinfo@diurnal.co.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 No
    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/3/05/296
    D.3 Description of the IMP
    D.3.1Product nameChronocort®
    D.3.2Product code DIURF-006
    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 INNHYDROCORTISONE
    D.3.9.1CAS number 50-23-7
    D.3.9.3Other descriptive nameCortisol
    D.3.9.4EV Substance CodeSUB08065MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number5 to 20
    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
    Congenital adrenal hyperplasia (CAH); is generally due to 21-hydroxylase deficiency, is a disease of the adrenal cortex characterised by cortisol deficiency with or without aldosterone deficiency, and androgen excess. Subjects with CAH are at risk of developing a number of clinical manifestations, such as obesity in children, insulin resistance, and polycystic ovaries, which may contribute to infertility in women with CAH. Oligomenorrhoea or amenorrhoea may be present in adolescence.
    E.1.1.1Medical condition in easily understood language
    CAH is a group of inherited conditions that are present at birth where the body is missing a chemical substance that allows the adrenal glands to release the cortisol hormone.
    E.1.1.2Therapeutic area Diseases [C] - Hormonal diseases [C19]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10010323
    E.1.2Term Congenital adrenal hyperplasia
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess safety and tolerability of Chronocort® over time, as assessed by signs and symptoms of adrenal insufficiency or over-treatment, use of sick day rules, adrenal crisis, adverse events (AEs), laboratory measures and clinical observation.
    E.2.2Secondary objectives of the trial
    The long-term efficacy of Chronocort® will be assessed over time by the measurement of:
    1. Total daily dose in mg/day of hydrocortisone during the study and the incidence of dose titrations
    2. 17-hydroxyprogesterone (17-OHP) and androstenedione (A4), measured at two time points (at 09:00 and 13:00 hours) for:
    a. Disease control at each visit as assessed by both 17-OHP and A4 levels in the optimal and normal range, respectively, at both time points.
    b. 17-OHP and A4 standard deviation scores
    c. Change in absolute values compared to pre-Chronocort® baseline values
    3. Changes compared to pre-Chronocort® baseline in:
    a. Bone turnover markers - serum C-terminal cross-linked telopeptide, osteocalcin
    b. Testosterone
    c. Fasting insulin and blood glucose levels and glycated haemoglobin
    d. High sensitivity c-reactive protein and plasma renin activity
    e. Body composition (dual energy X-ray absorptiometry)
    f. Quality of life – SF-36®, Multidimensional Assessment of Fatigue, EQ-5D™
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subjects with congenital adrenal hyperplasia (CAH) who have successfully completed the DIUR-003 or DIUR-005 clinical trials with the current formulation of Chronocort®
    2. Provision of signed written informed consent.
    E.4Principal exclusion criteria
    1. Co-morbid condition requiring daily administration of a medication (or consumption of any material) that interferes with the metabolism of glucocorticoids
    2. Clinical or biochemical evidence of hepatic or renal disease. Creatinine over twice the ULN or elevated liver function tests (ALT or AST >2 times the ULN)
    3. Subjects on regular daily inhaled, topical, nasal or oral steroids for any indication other than CAH
    4. History of malignancy (other than basal cell carcinoma successfully treated >6 months prior to entry into the study)
    5. Participation in another clinical trial of an investigational or licensed drug or device within the 3 months prior to inclusion in this study
    6. Subjects with a history of bilateral adrenalectomy
    7. Subjects unable to comply with the requirements of the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the safety of Chronocort® over time, assessed using but not limited to the following endpoints throughout the study:
    1. Signs and symptoms of adrenal insufficiency or over-treatment
    2. Use of sick day rules
    3. Occurrence of adrenal crises
    4. Occurrence of AEs
    5. Change from pre-Chronocort® baseline in safety laboratory assessments at each visit
    6. Change from pre-Chronocort® baseline in vital signs, weight, body mass index, and waist circumference at each visit.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Each visit throughout the study
    E.5.2Secondary end point(s)
    The following secondary endpoints will be assessed (seeking to assess long term efficacy):
    1. Total daily dose of Chronocort® in mg/day of hydrocortisone
    2. Disease control throughout the study as assessed by both 17-OHP and A4 levels in the optimal and normal range, respectively
    3. Change from pre-Chronocort® baseline at each visit in SDS of 17-OHP and A4 and the mean of the two timepoints
    4. Change from pre-Chronocort® baseline at each visit in the absolute values of 17-OHP and A4
    5. Change from pre-Chronocort® baseline at each visit in:
    a. Bone turnover markers - CTX, osteocalcin
    b. Testosterone (total)
    c. Fasting insulin and blood glucose levels, and HbA1c
    d. hsCRP and PRA
    g. Body composition (DEXA)(fat mass, lean mass and total bone density)
    e. Quality of life – SF-36®, MAF, EQ-5D™
    6. Incidence of dose titrations.
    E.5.2.1Timepoint(s) of evaluation of this end point
    At all visits:
    1. Measurement of 17-OHP and A4 at two time points (the first at 09:00 and the second at 13:00 hours).

    At baseline, at each 6-monthly visit and at the final visit:
    1. Physical examination, vital signs, weight, BMI and waist circumference.
    2. Safety blood tests, serum CTX, osteocalcin, PRA, hsCRP, HbA1c, testosterone,
    fasting insulin and blood glucose levels.
    3. Quality of life – SF-36®, MAF, EQ-5D™

    At yearly intervals:
    1. Body composition (DEXA)(fat mass, lean mass and total bone density) (also taken at baseline for subjects entering from study DIUR-003).
    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 Yes
    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) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    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 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.8.2.4Number 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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA9
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Denmark
    France
    Germany
    Netherlands
    Sweden
    United Kingdom
    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
    The final telephone call (30 days after the last visit) of the last subject
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months4
    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.1.1.1In 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) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 136
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2016-07-05. Yes
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 118
    F.4.2.2In the whole clinical trial 136
    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)
    Subjects will continue in the study for a maximum of 3.5 years. If after this time point a decision has not been reached concerning a marketing authorisation for Chronocort®, a further extension of the study through a protocol amendment may be considered.
    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 Decision2016-07-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-07-20
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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