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    Summary
    EudraCT Number:2012-001104-37
    Sponsor's Protocol Code Number:ME/2011/3709
    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:2014-07-24
    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 number2012-001104-37
    A.3Full title of the trial
    Pulsed glucocorticoid replacement therapy for patients with adrenocortical insufficiency secondary to Addison’s disease and congenital adrenal hyperplasia
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    pulses study
    A.3.2Name or abbreviated title of the trial where available
    the pulses study
    A.4.1Sponsor's protocol code numberME/2011/3709
    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 Hospitals Bristol NHS Foundation Trust
    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.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity of Bristol
    B.5.2Functional name of contact pointStafford Lightman
    B.5.3 Address:
    B.5.3.1Street AddressDHB, HWLINE, Whitson St
    B.5.3.2Town/ cityBristol
    B.5.3.3Post codeBS1 3NY
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number(0)117 331 3167
    B.5.5Fax number(0)117 331 3169
    B.5.6E-mailStafford.Lightman@bristol.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 hydrocortisone sodium phosphate
    D.2.1.1.2Name of the Marketing Authorisation holderAmdipharm Plc
    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 namehydrocortisone sodium phosphate
    D.3.4Pharmaceutical form Solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNhydrocortisone sodium phosphate
    D.3.9.1CAS number 6000 74 4
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 hydrocortisone
    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 namehydrocortisone
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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.3.9.4EV Substance CodeAS3
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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 placeboSolution for injection/infusion
    D.8.4Route of administration of the placeboSubcutaneous use
    D.8 Placebo: 2
    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
    Addison's disease and Congenital Adrenal Hyperplasia
    E.1.1.1Medical condition in easily understood language
    diseases where the body is unable to produce the hormone cortisol
    E.1.1.2Therapeutic area Diseases [C] - Hormonal diseases [C19]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    E.1.2Level LLT
    E.1.2Classification code 10011195
    E.1.2Term Cortisol
    E.1.2System Organ Class 100000004848
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    E.1.2Level LLT
    E.1.2Classification code 10020518
    E.1.2Term Hydrocortisone
    E.1.2System Organ Class 100000004848
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the hormonal responses of patients with Addison's disease and congenital adrenal hyperplasia on standard oral and pulsatile subcutaneous hydrocortisone replacement therapy.
    E.2.2Secondary objectives of the trial
    To compare the metabolic, psychological (cognitive and emotional processing) and quality of life measures of patients with Addison's disease and congenital adrenal hyperplasia on standard oral replacement and pulsatile subcutaneous hydrocortisone replacement therapy.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Male and female patients with confirmed Addison’s disease and CAH
    Aged 18 to 64 years
    Females of child bearing potential must be using a highly effective method of contraception / birth control as defined in ICH (M3) if sexually active
    Right handed
    Able to give informed consent
    E.4Principal exclusion criteria
    Any significant current cerebral, cardiovascular, respiratory, hepatobiliary, pancreatic disease, renal dysfunction, gastrointestinal emptying or motility disturbances.
    No current treatment or within the last 3 months of another underlying disease that could necessitate treatment with glucocorticoids
    Taking of medications that interfere with cortisol metabolism (antiepileptics, St Johns wart, rifampicin)
    Diagnosis of Addison’s disease less than 6 months ago
    Pregnant or lactating women
    Greater than 21 units of alcohol per week
    Taking of any investigational drug within the past two months
    Known allergy to any of the study medications and /or materials used in the pump
    Needle phobia
    Contraindication to fMRI scan i.e. metal implant/shrapnel
    Claustrophobia
    Left handed/ambidextrous
    Dyslexia
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome measure is to achieve a physiological cortisol circadian and ultradian rhythms with adequate suppression of ACTH on waking in both AD and CAH patients, and of morning 17-OHP levels in CAH.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline and 6 week blood samples for ACTH, cortisol and 17-OHP/androstenedione (CAH only)
    24 hour blood samples for ACTH, cortisol and cortisone (10 minute all patients), POMC (hourly all patients), 17-OHP (1-3 hourly CAH only) profiles. This is an optional study during week 6-7.
    E.5.2Secondary end point(s)
    The secondary objective is to be able to demonstrate this intervention improves metabolic parameters, health related quality of life, fatigue, general well being, working memory and emotional and cognitive processing
    E.5.2.1Timepoint(s) of evaluation of this end point
    In each study arm
    Metabolic parameters - metabolic blood profile (baseline and week 6), weekly body composition, BP and weight.
    Standardized patient questionnaires for subjective assessment of well-being (main outcome in comparison to baseline)
    Beck’s inventory of depression scale (baseline only)
    SF36, Chalder Fatigue Scale, ICFS and AdQuoL (at week -1, 1 and 6)
    PANAS (at week -1, 1 and 6 )
    PSQI (at week -1, 1 and 6 ) and LSEQ (weekly)
    Ecological Momentary assessment (main outcome, to be collected daily )
    Laboratory based psychological tests and fMRI scan (main outcome, week 6)
    N-Back task (main outcome in comparison to baseline, week 1 and 6)
    Actigraphy and sleep diary (main outcome, in comparison to baseline and transition 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 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 No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    cognitive and Quality of Life assessment
    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 Yes
    E.8.1.7Other No
    E.8.1.7.1Other trial design description
    placebo controlled
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    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.8.5The 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 No
    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
    completion of study report - due to the nature of the study we will be taking multiple blood samples which will have to be stored until analysis. We will not know if there is a technical problem with the samples until they are processed.
    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 months3
    E.8.9.1In the Member State concerned days29
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days29
    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: 20
    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 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)
    As this is in a purely experimental setting and the product is not yet licensed subcutaneously for the treatment of adrenal insufficiency there is no arrangement for continued provision of the intervention.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation CRN West of England
    G.4.3.4Network Country United Kingdom
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-09-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-10-06
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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