Diabetes Melitus Type 2 MedDRA version: 20.0 Level: HLGT Classification code 10018424 Term: Glucose metabolism disorders (incl diabetes mellitus) System Organ Class: 10014698 - Endocrine disorders MedDRA version: 20.0 Level: PT Classification code 10012601 Term: Diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Forxiga
Product Name: Dapagliflozin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: INN-dapagliflozin
CAS Number: 461432-26-8
Other descriptive name: DAPAGLIFLOZIN
Concentrati
Sponsors
Universitätsklinikum Tübingen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Type 2 diabetes •Age 18 - 75 years •Anti-GAD antibodies negative •C-peptide levels = 1.5 ng/mL •Fasting blood glucose = 126 mg/dl •HbA1c 8.0 – 10.5 % •BMI 25.0 – 45.0 kg/m2 •Previous therapy with standard BBIT (basal insulin and at least once daily bolus insulin) when the bolus insulin dose is not adjusted to exercise or nutrient intake. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: •Use of any oral antidiabetic treatment except for metformin (i.e., sulphonylureas, DPP-IV inhibitors, thiazolidinediones, SGLT-2 inhibitors) or GLP-1 analogues within the last three months prior to Screening •Repeated episodes of severe hypoglycaemia within the last six months prior to Screening •History of diabetic ketoacidosis, praecoma diabeticum, or diabetic coma •Treatment with any other investigational drug within the last three months before Screening •Acute infections within the last four weeks prior to Screening •Recurrent urogenital infections •History of pancreatitis •Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures •History of severe or multiple allergies •Concomitant participation in other clinical trials •Type 1 diabetes •Cardiovascular disease Clinically relevant ventricular tachycardia or ventricular fibrillation, 3rd degree AV block or Torsades de Pointes or treatment with antiarrhythmic drugs. Percutaneous coronary intervention within the past 6 months. Any of the following within the past 6 months: myocardial infarction (MI), coronary artery bypass surgery; unstable angina; or stroke. Uncontrolled unstable angina pectoris or history of pericarditis, myocarditis, endocarditis. Congestive heart failure NYHA class III or IV. Increased risk of thromboembolism, e.g. subjects with a history of deep leg vein thrombosis or family history of deep leg vein thrombosis, as judged by the Investigator. •Malignancy including leukemia and lymphoma within the last 5y. •Liver disease such as cirrhosis or chronic active hepatitis. •Moderate or severe impaired liver function (serum AST or serum ALT > 2.5 x ULN, serum total bilirubin = 2.0 mg/dl or serum albumin = 3.5 g/dl) •Significant renal dysfunction (see also exclusion criteria laboratory abnormalities). •State after kidney transplantation •Endocrine disease: Acromegaly or treatment with growth hormone or similar drugs. Chronic oral or parenteral corticosteroid treatment (=7 consecutive days of treatment) within 8 weeks; thyroid hormone replacement is allowed if the dosage has been stable for at least 3 months and the TSH is within normal limits •Any of the following significant laboratory abnormalities: eGFR (as calculated by the MDRD equation) 12g/day for women and >24g/day for men) within the past 2 years. •Pregnancy or childbearing potential without adequate contraception •Present therapy with systemic steroids •Known hypersensitivity to Dapagliflozin or Saxagliptin or any of the components of their formulation or human nasal insulin or any of the components of its formulation •Immune suppressive medication and/or immune deficiency syndromes •Presence of psychiatric disorder or intake of anti-depressive or anti-psychotic agents with the exception of benzodiazepines and SSRIs/SNRI´s •Potentially unreliable subjects, and those judged by the investigator to be unsuitable for the study (e.g. subjects needing assistance for the application of insulin, subjects deemed not to be compliant with the recommendations given during the study) •Contraindications for Magnetic resonance (MR) scanning such as persons with cardiac pacemaker and implants out of metal or claustrophobia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of adding the SGLT2 inhibitor dapagliflozin + the DPP-4 inhibitor saxagliptin vs placebo to revert from a standard basal-bolus insulin treatment (BBIT) regimen to a basal supported oral therapy (BOT) regimen in patients with type 2 diabetes. Percentage of subjects achieving a HbA1c = 7.5% and having a reversal from a BBIT to a BOT regimen;Secondary Objective: To determine the efficacy of adding the SGLT2 inhibitor dapagliflozin + the DPP-4 inhibitor saxagliptin vs placebo to a standard BBIT regimen to improve glycemic parameters, insulin dose, bodyweight, body fat mass and body fat distribution, blood pressure, lipid profile, microalbuminuria, quality of life, brain insulin resistance and blood parameters of cardiometabolic risk. To evaluate the safety and tolerability of adding the SGLT2 inhibitor dapagliflozin + the DPP-4 inhibitor saxagliptin vs placebo to a standard BBIT regimen.;Primary end point(s): Percentage of subjects achieving a HbA1c = 7.5% and having a reversal from a BBIT to a BOT regimen;Timepoint(s) of evaluation of this end point: Visit 4: Week 0: On-site visit, dose adjustment Visit 6: Week 2: On-site visit, dose adjustment Visit 10: Week 8: On-site visit, dose adjustment Visit 14: Week 16: On-site visit, dose adjustment Visit 18.1: Week 24-day 1: Final visit, outcome parameters Visit 18.2: Week 24-day 2: Final visit, outcome parameters | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Visit 4: Week 0: On-site visit, dose adjustment Visit 6: Week 2: On-site visit, dose adjustment Visit 10: Week 8: On-site visit, dose adjustment Visit 14: Week 16: On-site visit, dose adjustment Visit 18.1: Week 24-day 1: Final visit, outcome parameters Visit 18.2: Week 24-day 2: Final visit, outcome parameters;Secondary end point(s): changes in HbA1c between groups • changes in hypoglycaemic events between groups • changes in fasting blood glucose between groups • changes in daily insulin dose between groups • changes in bodyweight between groups • changes in body fat content and body fat distribution, both precisely measured with MR tomography, and liver fat content, precisely measured with 1H-MR spectroscopy, and intra-nasal insulin-induced brain fMR imaging results between groups (to be discussed – decreased insulinemia and lower energy availability are expected to decrease visceral fat mass and liver fat content and to improve brain insulin resistance) • changes in blood pressure between groups • changes in the blood lipid profile between groups • changes in well being and disease perception between groups. • changes in fear of hypoglycaemia AEs/SAEs Vital signs Collection of clinical chemistry/haematology parameters ECGs. The following parameters will be recorded for each ECG: date and time of ECG, heart rate (beats/min), QT (ms), QTcB (ms), sinus rhythm (yes/no), and overall evaluation (normal/abnormal) | — |
Countries
Germany
Contacts
Public ContactProf. Dr. Norbert Stefan
Universitätsklinikum Tübingen
Outcome results
None listed