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    The EU Clinical Trials Register currently displays   41501   clinical trials with a EudraCT protocol, of which   6826   are clinical trials conducted with subjects less than 18 years old.
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    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:2016-002212-41
    Sponsor's Protocol Code Number:ESR-15-11453
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-08-04
    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 ConcernedGermany - BfArM
    A.2EudraCT number2016-002212-41
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-controlled, Single-center Phase 1 Inpatient Pilot Study to Explore the Safety and Efficacy of DAPAglifozin as Add-on to day and night closed-loop control using the DreaMed Substance Administration Device Software in Adolescent and Adult Subjects with Type 1 Diabetes mellitus
    Randomisierte, doppel-blinde, Plazebo-kontrollierte, monozentrische, Phase 1-Studie zur Untersuchung der Sicherheit und Wirksamkeit von Dapagliflozin als Zusatztherapie zu einem closed loop System (tagsüber und nachts) unter der Kontrolle des automatisierten DreamMed Systems bei jugendlichen und erwachsenen Patienten mit Typ 1 Diabetes mellitus.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Randomized, Double-Blind, Placebo-controlled, Single-center Phase 1 Inpatient Pilot Study to Explore the Safety and Efficacy of DAPAglifozin as Add-on to day and night closed-loop control using the DreaMed Substance Administration Device Software in Adolescent and Adult Subjects with Type 1 Diabetes mellitus
    Randomisierte, doppel-blinde, Plazebo-kontrollierte, monozentrische, Phase 1-Studie zur Untersuchung der Sicherheit und Wirksamkeit von Dapagliflozin als Zusatztherapie zu einem closed loop System (tagsüber und nachts) unter der Kontrolle des automatisierten DreamMed Systems bei jugendlichen und erwachsenen Patienten mit Typ 1 Diabetes mellitus.
    A.3.2Name or abbreviated title of the trial where available
    DapaDream
    A.4.1Sponsor's protocol code numberESR-15-11453
    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 SponsorStiftung Hannoversche Kinderheilanstalt, Kinder - und Jugendkrankenhaus AUF DER BULT, Diabeteszentrum für Kinder - und J
    B.1.3.4CountryGermany
    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 supportAstra Zeneca
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationStiftung Hannoversche Kinderheilanstalt, Kinder - und Jugendkrankenhaus AUF DER BULT, Diabeteszentrum für Kinder - und J
    B.5.2Functional name of contact pointDeputy Principal Investigator
    B.5.3 Address:
    B.5.3.1Street AddressJanusz-Korczak-Allee 12
    B.5.3.2Town/ cityHannover
    B.5.3.3Post code30173
    B.5.3.4CountryGermany
    B.5.4Telephone number004951181153344
    B.5.5Fax number00495118115993344
    B.5.6E-mailbiester@hka.de
    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 Forxiga
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca AB
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameForxiga
    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 INNDapagliflozin
    D.3.9.1CAS number 461432-26-8
    D.3.9.3Other descriptive nameDAPAGLIFLOZIN
    D.3.9.4EV Substance CodeSUB31650
    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
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    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
    Type 1 Diabetes mellitus
    E.1.1.1Medical condition in easily understood language
    Type 1 Diabetes mellitus in adults and adolescents
    E.1.1.2Therapeutic area Diseases [C] - Hormonal diseases [C19]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The purpose of the pilot study is to collect clinical data of a single-dose of 10mg dapagliflozin as add-on to night and day closed-loop control using the DreaMed Algorithm on the time within glucose range 70-180 mg/dl (3.9-10mmol/l) [%] for the ensuing 24 hours with two oral mixed-meals.
    E.2.2Secondary objectives of the trial
    • To investigate the degree of insulin dose reduction during the DreaMed automated insulin delivery 24 hours after a single dose of 10mg dapagliflozin in patients with type 1 diabetes
    • To investigate the effect on urinary glucose excretion
    • To investigate if dapagliflozin influences postprandial insulin need
    • To investigate if dapagliflozin is associated with elevated ß-hydroxybutyrate levels
    • One extra sample will be taken potentially for additional analysis of the incretin axis (for example GIP) in case that elevated β-Hydroxyburate levels need to be elucidated further
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female aged 12-21 years (both inclusive)
    2. Type 1 diabetes mellitus (as diagnosed clinically) ≥ 12 months
    3. No DKA 12 weeks prior to the study
    4. On CSII (insulin pump therapy) since at least 3 months
    5. Average daily dose of Insulin between 0.6 – 2.0 U/kg
    6. Body mass index 18 to 35 kg/m2 or the 10th to 99th centile for BMI according to age and gender with a minimum weight of 50kg
    7. A1c range 6,5% – 11% (inclusive)
    E.4Principal exclusion criteria
    1. Anamnestic history of hypersensitivity to the study drugs (or any component of the study drug) or to drugs with similar chemical structures
    3. History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT > 3 times the normal reference range), renal (creatinine > 1.1 mg/dl in women and > 1.5 mg/dl in men), neurological, psychiatric and/or hematological disease as judged by the investigator
    9. Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study
    10. History of T2DM, maturity onset diabetes of young (MODY), pancreatic surgery or chronic pancreatitis
    11. Any use of oral hypoglycemic agents within 12 months prior to the screening visit
    12. History of diabetes ketoacidosis (DKA) within 12 weeks prior to prior to the screening visit
    13. History of diabetes insipidus
    14. History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 3 months prior to prior to the screening visit
    15. Frequent episodes of hypoglycemia as defined by more than one episode requiring assistance, emergency care (paramedics or emergency room care) or glucagon therapy, or more than 2 unexplained episodes of symptomatic hypoglycemia within 3 months prior to the screening visit. 16. Hypoglycemic unawareness
    History of Addison’s disease or chronic adrenal insufficiency
    18. Aspartate aminotransferase (AST) > 2X Upper limit of normal (ULN)
    19. Alanine aminotransferase (ALT) > 2X ULN
    20. Serum total bilirubin > 2X ULN
    21. Estimated GFR (eGFR) by the Modification of Diet in Renal Disease (MDRD)
    24. Hemoglobin ≤ 11.0 g/dl (110 g/l) for boys / men; hemoglobin ≤10.0 g/dl (100 g/L) for girls / women.
    25. Creatine kinase (CK) > 3X ULN
    27. Abnormal Free T4 Note: abnormal TSH value at screening will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded. A one-time retest may be allowed, as determined by the Investigator, after a minimum of 6 weeks following the adjustment of thyroid hormone replacement therapy in subject who have had a prior diagnosis of a thyroid disorder and who are currently receiving thyroid replacement therapy. Such cases should be discussed with the Investigator prior to retesting. The subject must have all screening procedures and laboratory assessments performed as part of this re-test, and all of these must meet enrolment eligibility criteria. The subject’s number will, however, remain the same as initially assigned.
    28. Allergies or contraindication to the contents of dapagliflozin tablets or insulin
    29. Renal, Hepatic, Hemotological/Oncological Diseases/Conditions
    30. History of unstable or rapidly progressing renal disease
    31. Conditions of congenital renal glucosuria
    32. Renal allograft
    33. Significant hepatic disease, including but not limited to, chronic active hepatitis and/or severe hepatic insufficiency
    34. Documented history of hepatotoxicity with any medication
    35. Documented history of severe hepatobiliary disease
    36. History of hemoglobinopathy, with the exception of sickle cell trait (SA) or thalassemia minor; or chronic or recurrent hemolysis
    52. No clinical conditions or clinically significant abnormalities, in any laboratory value(s) collected after screening and prior to randomization which, in the Investigator’s judgment, should preclude entry into the treatment period.
    53. Subjects who meet one or more of the dosing day exclusion criteria will be excluded from the dosing visit or withdrawn from the trial as specified below:
    54. Non-fasting, ie, consumption of food or beverages other than water, later than at 23:00 hours the evening before dosing.
    55. Clinically significant illness with onset within 4 weeks prior to dosing
    56. Presence of clinically significant acute gastrointestinal symptoms (eg nausea, vomiting, heartburn or diarrhoea), as judged by the investigator
    57. Consumption of alcohol within 24 hours prior to dosing
    58. Episode of severe hypoglycemia occurring within the last 24 hours prior to dosing
    59. Any medical condition that, in the opinion of the Investigator, could interfere with insulin pharmacokinetics and/or glucose metabolism.
    60. Use of the following: systemic (oral or i.v.) corticosteroids, monoamine oxidase (MAO) inhibitors, systemic non-selective beta-blockers, growth hormone, non-routine vitamins or herbal products. Furthermore, thyroid hormones are not allowed unless the subject has used stable medication during the past 3 months.
    61. Non-adherence to pre-dosing insulin regimen consisting of CSII
    62. Subjects who meet one or more of dosing day exclusion criteria will be excluded from the dosing visit. In case a subject is excluded from the dosing visit, the dosing visit can be rescheduled 1–7 days later. Each of the dosing visits can only be rescheduled once.

    E.5 End points
    E.5.1Primary end point(s)
    Time within glucose range 70-180 mg/dl (3.9-10mmol/l) [%] during night and day closed-loop control using the DreaMed automated insulin delivery with two oral mixed-meals after oral administration of 10mg dapagliflozin
    E.5.1.1Timepoint(s) of evaluation of this end point
    Visit 2 and visit 4
    E.5.2Secondary end point(s)
    • Percentage of glucose sensor readings below 70 mg/dl (3.9 mmol/l)
    • Percentage of glucose sensor readings above 180mg/dl (10 mmol/l)
    • Average and SD of glucose sensor readings
    • Percentage of elevated ß-hydroxybutyrate-levels in blood
    • Insulin need during the DreaMed automated insulin delivery
    E.5.2.1Timepoint(s) of evaluation of this end point
    Visit 2 and Visit 4
    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 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
    PK in adolescents (off label)
    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 Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over Yes
    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.8.5The 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
    After 30 subjects have completed visit 6.
    Certain circumstances may lead to early termination of an entire study, in particular for ethical or safety reasons such as:
    - The high frequency and/or unexpected severity of adverse events.
    - Unsatisfactory recruitment of patients as far as their quantity or quality is concerned or recurrent incomplete/inappropriate collection of data.
    The decision to prematurely terminate the study will be made by the Sponsor.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned 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: 15
    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) Yes
    F.1.1.6.1Number of subjects for this age range: 15
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 15
    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 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 Yes
    F.3.3.7.1Details of other specific vulnerable populations
    under age 18 - adolescents
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    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)
    Visit 6, the follow-up visit will take place 7–21 days after the end of Visit 4. Last Treatment occured in visit 4. Visit 5 is a phone call (3-5 days after treatment has stopped) to follow up in regards to safety and finally vist 6 takes place.
    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 Decision2016-09-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-12-06
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-12-19
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