Type 1 Diabetes Mellitus MedDRA version: 19.0 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Signed informed consent - Diagnosis of T1DM. In addition, a central laboratory C-peptide =65 years) yes F.1.3.1 Number of subjects for this age range 372
Exclusion criteria
Exclusion criteria: o History of T2DM Note: subjects with a previous misdiagnosis of T2DM in their medical history must have one of the following in order to be eligible for this trial: -Positive autoantibodies for GAD65, phosphatase IA-2/IA2ß, or ZnT8 -Fasting c-peptide value below the lower limit of detection performed by the Lab o History of maturity onset diabetes of young o Pancreatic surgery, chronic or other pancreatic disorders that could result in decreased ß-cell capacity o Previous use of DAPA and/or any other SGLT-2 inhibitors o Use of insulin-sensitizing agents, such as metformin and/or thiazolidinediones, within 2 months prior to the screening o Use of any GLP-1 receptor agonist within the following timeframe prior to the screening: i) 1 month for once or twice daily administration ii) 2 months for once weekly administration o Any non-insulin, antihyperglycemic agent use within 1 month prior to the Screening o History of DKA requiring medical intervention within 1 month prior to the screening o History of hospital admission for glycemic control within 1 month prior to the Screening o Frequent episodes of severe hypoglycemia as defined by more than one episode requiring medical assistance, emergency care, and/or glucagon therapy administered by a third-party individual within 1 month prior to the screening o Symptoms of poorly controlled diabetes that would preclude participation in this trial including but not limited to marked polyuria and polydipsia with greater than 10% weight loss during the 3 months prior to screening o History of Addison’s disease or chronic adrenal insufficiency o History of diabetes insipidus o Any of the following cardiovascular/vascular diseases within 6 months of the screening: - Myocardial infarction - Cardiac surgery or revascularization - Unstable angina - Unstable congestive heart failure - CHF New York Heart Association Class III or IV -TIA or significant cerebrovascular disease - Unstable or previously undiagnosed arrhythmia o Renal Disease: - History of unstable or rapidly progressing renal disease - Conditions of congenital renal glucosuria - Renal allograft o Hepatic Diseases: - Significant hepatic disease o Hematological and Oncological Disease/Conditions: - History of hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis - Known immunocompromised status, individuals who have undergone organ transplantation or who are positive for the HIV - Donation of blood or blood products to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of > 400 mL of blood during the 8 weeks prior to the screening visit - Malignancy within 5 years of the screening visit - History of bladder cancer - History of radiation Th to the lower abdomen or pelvis at any time
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to compare the change from baseline in HbA1c between dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment. ; Primary end point(s): The primary endpoint of this study is the change in HbA1c from baseline to Week 24. ;Timepoint(s) of evaluation of this end point: The timepoint will be evaluated on specified visits per schedule of assessments, please section 5.1 in protocol; Secondary Objective: -Compare % change in total daily insulin dose with DAPA 5or10 mg + insulin vs placebo + insulin after 24w -% change in BW with DAPA 5or10 mg + insulin vs placebo + insulin after 24w -The change in value of 24h glucose from CGM with dapagliflozin 5 or10 mg + insulin vs placebo + insulin after 24w -The change in MAGE of 24-hour glucose from CGM with DAPA 5or10 mg plus insulin vs placebo + insulin after 24w -The change in the percent of 24h glucose from CGM that falls within the target range of >70 mg/dL and =180 mg/dL with DAPA 5or10 mg + insulin vs placebo plus insulin after 24w -Compare DAPA 5or10 mg + insulin vs placebo + insulin for the proportion of achieving an HbA1c reductionfrom baseline to W24 visit = 0.5% without severehypoglycemia -Proportion of hypoglycemia and the frequency and severity of the hypoglycemia with DAPA 5or10 mg + insulin vs placebo + insulin -Safety&tolerability by assessment of AE, vital signs, DKA, physical and lab findings | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percent change from baseline to Week 24 in total daily insulin dose 2. Percent change from baseline to Week 24 in body weight 3. Change from baseline to Week 24 in the mean value of 24-hour glucose readings obtained from CGM 4. Change from baseline to Week 24 in mean amplitude of glucose excursion (MAGE) of 24-hour glucose readings obtained from CGM 5. Change from baseline to Week 24 in the percent of 24-hour glucose readings obtained from CGM that falls within the range of > 70 mg/dL and ? 180 mg/dL 6. Proportion of subjects achieving an HbA1c reduction from baseline to Week 24 = without severe hypoglycemia events. ;Timepoint(s) of evaluation of this end point: The timepoint will be evaluated on specified visits per schedule of assessments, please see section 5.1.1 in protocol | — |
Countries
Argentina, Belgium, Canada, Chile, Germany, Japan, Netherlands, Poland, Russian Federation, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed