Type 2 Diabetes Mellitus
Conditions
Keywords
DPP-4 inhibitor, HbA1c, Incretin, Dapagliflozin
Brief summary
This is a 24-week, multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group, phase 3 study designed to evaluate if the safety and efficacy of dapagliflozin 5 mg or 10 mg added to saxagliptin 5 mg plus metformin is superior to placebo added to saxagliptin 5 mg plus metformin in reducing hemoglobin A1c (HbA1c).
Detailed description
This study will be conducted in approximately 36 sites in Asian countries. Approximately 1004 subjects will be screened and 342 randomized. Prior to the screening, subjects of Stratum A should have a stable dose of metformin (≥1500 mg/day or a maximal tolerated dose) for at least 8 weeks. And subjects of Stratum B should have a stable dose of metformin (≥1500 mg/day or a maximal tolerated dose) AND a dipeptidyl peptidase-4 inhibitor at maximum approved dose for at least 8 weeks prior to the screening. Eligible subjects who complete the screening visit will enter the lead-in period, which includes open-label saxagliptin 5 mg and metformin treatment for 16 weeks in Stratum A or 8 weeks in Stratum B. At randomization visit, eligible subjects will be randomized into 1 of 3 treatment groups in a 1:1:1 ratio, receiving blinded dapagliflozin 5 mg, 10 mg or placebo plus metformin and saxagliptin 5 mg treatment for 24 weeks.
Interventions
DRUGDapagliflozin 10 mg
10 mg, oral tablet, once daily for 24 weeks of double-blind treatment period
5 mg, oral tablet, once daily for 24 weeks of double-blind treatment period
DRUGDapagliflozin 10 mg placebo to match
10 mg, oral tablet, once daily for 24 weeks of double-blind treatment period
DRUGDapagliflozin 5 mg placebo to match
5 mg, oral tablet, once daily for 24 weeks of double-blind treatment period
DRUGSaxagliptin 5 mg
5 mg, oral tablet, once daily for 24 weeks of double-blinded treatment period, and for 16 weeks of open-label treatment period in Stratum A or 8 weeks of open-label treatment period in Stratum B
DRUGMetformin
Stable dose of metformin immediate release/extended release (≥ 1500 mg/day or at a maximal tolerated dose) throughout the whole study period
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of informed consent before participating in the study 2. Diagnosed with type 2 diabetes mellitus 3. Inadequate glycemic control defined as below: * HbA1c ≥ 8.0% and ≤ 11.5% for Stratum A and HbA1c ≥ 7.5% and ≤ 10.5% for Stratum B at screening visit * HbA1c ≥ 7.0 and ≤ 10.5% for both strata at Week -2 visit 4. Body mass index ≤ 40.0 kg/m\^2
Exclusion criteria
1. Women of childbearing potential unable or unwilling to use acceptable birth control, or women who are pregnant or breastfeeding 2. History of diabetes insipidus and type 1 diabetes 3. History of diabetic ketoacidosis requiring medical intervention within 1 month prior to screening 4. Subjects with moderate to severe renal impairment (defined as estimate glomerular filtration rate calculated by the MDRD Formula \< 60mL/min/1.73 m\^2 or serum creatinine ≥ 1.5 mg/dL in males or ≥ 1.4 mg/dL in females) or end-stage renal disease 5. History of unstable or rapidly progressing renal disease 6. Subjects with significant hepatic disease or severe hepatic impairment, or positive serologic evidence of current infectious liver disease 7. Prohibited Treatment and Therapies * Administration of any anti-hyperglycemic therapy \[other than metformin, or Dipeptidyl peptidase-4 (DPP-4) inhibitors\] for more than 14 days (consecutive or not) during the 8 weeks prior to screening * Any use of Sodium glucose cotransporter 2 (SGLT2) inhibitor within 8 weeks prior to screening * Prescription and over-the-counter weight loss medications within 3 months prior to screening * Current treatment with potent cytochrome P450 3A4/5 inhibitors 8. Malignancy within 5 years of the screening 9. History of hemoglobinopathy 10. Hematuria (by microscopy) positive at screening visit 11. FPG \> 270 mg/dL obtained at open-label period 12. An abnormal TSH value at screening will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline in HbA1c at Week 24 | Baseline to Week 24 | To compare the mean change from baseline in HbA1c achieved with dapagliflozin 5 mg or dapagliflozin 10 mg added to saxagliptin 5 mg plus metformin versus placebo added to saxagliptin 5 mg plus metformin after 24 weeks of oral administration of double-blind treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline in fasting plasma glucose (FPG) at Week 24 | Baseline to Week 24 | To compare the mean change from baseline in FPG achieved with dapagliflozin 5 mg or dapagliflozin 10 mg added to saxagliptin 5 mg plus metformin versus placebo added to saxagliptin 5 mg plus metformin after 24 weeks of oral administration of double-blind treatment |
| Mean change in 2-hour postprandial glucose during a meal tolerance test (2-hour MTT) at Week 24 | Baseline to Week 24 | To compare the mean change from baseline in 2-hour postprandial glucose from a meal tolerance test (2-hour MTT) achieved with dapagliflozin 5 mg or dapagliflozin 10 mg added to saxagliptin 5 mg plus metformin versus placebo added to saxagliptin 5 mg plus metformin after 24 weeks of oral administration of double-blind treatment |
| Mean change from baseline in total body weight at Week 24 | Baseline to Week 24 | To compare the mean change from baseline in total body weight achieved with dapagliflozin 5 mg or dapagliflozin 10 mg added to saxagliptin 5 mg plus metformin versus placebo added to saxagliptin 5 mg plus metformin after 24 weeks of oral administration of double-blind treatment |
| Percent of subjects achieving a therapeutic glycaemic response of HbA1c <7.0% at Week 24 | At week 24 | To compare the proportion of subjects achieving a therapeutic glycaemic response of HbA1c \< 7.0% with dapagliflozin 5 mg or dapagliflozin 10 mg added to saxagliptin 5 mg plus metformin vs. placebo added to saxagliptin 5 mg plus metformin after 24 weeks of oral administration of double-blind treatment |
Countries
Thailand, Vietnam
Outcome results
None listed