AstraZeneca PLC — Xigduo EMA EPAR variation assessment report (EMEA/H/C/002672, 2014)
AstraZeneca PLC · 2014 · EMA EPAR variation assessment report · company profile →
Report summary
AstraZeneca AB submitted a Type II variation for dapagliflozin (Forxiga, Edistride) and dapagliflozin/metformin (Xigduo, Ebymect) in the EU, seeking to expand their indication for glycemic control to include prevention of new or worsening heart failure/cardiovascular death and nephropathy in adults with Type 2 Diabetes Mellitus. This was based on the Phase IIIb DECLARE-TIMI 58 study, which demonstrated dapagliflozin's superiority over placebo in reducing hospitalization for heart failure/CV death and renal composite endpoints, while showing non-inferiority for MACE. The study also improved renal parameters and HbA1c. Safety analysis revealed balanced rates of serious adverse events, with no increased risk of malignancies, fractures, or pancreatitis. While volume depletion and increased hematocrit were noted, no increased risk of amputations or serious UTIs was observed. The updated product information now reflects these cardiovascular and renal benefits.
Key findings — cited to the page
| Dapagliflozin approval date in EU | November 2012 | FORXIGA · EU · p.7 |
| Xigduo FDC approval date in EU | 16 January 2014 | XIGDUO FDC · EU · p.7 |
| Ebymect FDC approval date in EU | 16 November 2015 | EBYMECT FDC · EU · p.7 |
| Study phase | Phase IIIb | D1693C00001/DECLARE-TIMI 58 · p.7 |
| Comparator | placebo | D1693C00001/DECLARE-TIMI 58 · p.7 |
| Minimum age for inclusion | 40 years | D1693C00001/DECLARE-TIMI 58 · p.9 |
| HbA1c exclusion criterion | ≥12% or <6.5% % | D1693C00001/DECLARE-TIMI 58 · p.9 |
| Creatinine clearance exclusion criterion | <60 mL/min | D1693C00001/DECLARE-TIMI 58 · p.9 |
| Dapagliflozin dose | 10 mg | D1693C00001/DECLARE-TIMI 58 · p.10 |
| Predicted median duration of treatment period | 4.5 years | D1693C00001/DECLARE-TIMI 58 · p.10 |
| Primary events required for MACE superiority | 1390 | D1693C00001/DECLARE-TIMI 58 · p.11 |
| Type II variation application submission date | 8 January 2019 | EU · p.5 |
Source: AstraZeneca PLC ↗ · License: EMA - reuse permitted with acknowledgement. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Metabolic library →