Type 1 Diabetes mellitus
Conditions
Interventions
Trade Name: Forxiga
Product Name: Forxiga
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Dapagliflozin
CAS Number: 461432-26-8
Other descriptive name: DAPAGLIFLOZIN
Concentration unit: m
Sponsors
Stiftung Hannoversche Kinderheilanstalt, Kinder - und Jugendkrankenhaus AUF DER BULT, Diabeteszentrum für Kinder - und J
Eligibility
Sex/Gender
All
Inclusion criteria
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) Are the trial subjects under 18? yes Number of subjects for this age range: 15 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 crit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: • 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 ß-Hydroxyburate levels need to be elucidated further ;Primary 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;Timepoint(s) of evaluation of this end point: Visit 2 and visit 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary 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 ;Timepoint(s) of evaluation of this end point: Visit 2 and Visit 4 | — |
Countries
Germany
Contacts
Public ContactDeputy Principal Investigator
Stiftung Hannoversche Kinderheilanstalt, Kinder - und Jugendkrankenhaus AUF DER BULT, Diabeteszentrum für Kinder - und J
Outcome results
None listed