AstraZeneca and Bristol-Myers Squibb Company announced results from a Phase 3 study evaluating dapagliflozin in adult patients with type 2 diabetes who were inadequately controlled on combination treatment with metformin plus sulfonylurea. Dapagliflozin is a selective and reversible inhibitor of sodium-glucose cotransporter 2 (SGLT2), which works independently of insulin.
The study was a 24-week, randomized, double-blind, placebo-controlled study with an ongoing 28-week extension. The primary endpoint was mean change in HbA1c from baseline to week 24. In this study, 216 adult patients with type 2 diabetes, aged ≥ 18 years with inadequate glycemic control (HbA1c ≥7.0% and ≤10.5%) receiving metformin (≥ 1500 mg QD) and a maximum tolerated dose of sulfonylurea (at least half the maximum label dose for ≥8 weeks) were included. Patients were randomized to receive dapagliflozin 10mg (n=108) or placebo (n=108) for 24 weeks.
At the end of 24 weeks, patients treated with dapagliflozin 10mg added to metformin plus sulfonylurea demonstrated significantly greater improvements in glycemic control compared to those who received placebo, with a mean change from baseline in HbA1c of -0.86% (95% CI: -1.00, -0.72) in the dapagliflozin group vs. -0.17% (95% CI: -0.31, -0.02) in the placebo group (P <0.0001). Significant improvements were also seen in seated systolic blood pressure at eight weeks in patients treated with dapagliflozin compared to placebo.
A New Drug Application (NDA) resubmission for dapagliflozin was accepted for review by FDA in July 2013 with a new Prescription Drug User Fee Act (PDUFA) goal date of January 11, 2014.