Safety and Efficacy of Dapagliflozin in Asian T2DM Subjects With Inadequate Glycemic Control on Metformin/Saxagliptin

AstraZeneca

Status and phase: Terminated; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Dapagliflozin 5 mg; Drug: Saxagliptin 5 mg; Drug: Metformin; Drug: Dapagliflozin 10 mg placebo to match; Drug: Dapagliflozin 5 mg placebo to match; Drug: Dapagliflozin 10 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03608358

D1683C00008

Details and patient eligibility

About

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).

Full 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.

Enrollment: 41 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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41 participants in 3 patient groups, including a placebo group

Dapagliflozin 10 mg

Experimental group

Description:

Dapagliflozin 10 mg and dapagliflozin 5 mg placebo to match added to saxagliptin 5 mg and metformin

Treatment:

Drug: Metformin

Drug: Dapagliflozin 5 mg placebo to match

Drug: Saxagliptin 5 mg

Drug: Dapagliflozin 10 mg

Dapagliflozin 5 mg

Experimental group

Description:

Dapagliflozin 5 mg and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin

Treatment:

Drug: Metformin

Drug: Dapagliflozin 10 mg placebo to match

Drug: Dapagliflozin 5 mg

Drug: Saxagliptin 5 mg

Placebo

Placebo Comparator group

Description:

Dapagliflozin 5 mg placebo to match and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin

Treatment:

Drug: Metformin

Drug: Dapagliflozin 10 mg placebo to match

Drug: Dapagliflozin 5 mg placebo to match

Drug: Saxagliptin 5 mg