AstraZeneca PLC — Ebymect EMA EPAR variation assessment report (EMEA/H/C/004162, 2015)
AstraZeneca PLC · 2015 · EMA EPAR variation assessment report · company profile →
Report summary
AstraZeneca's Type II variation application for dapagliflozin-containing products (Forxiga, Xigduo, Edistride, Ebymect) sought to update therapeutic indications based on the DECLARE-TIMI 58 Phase IIIb study. This trial, involving Type 2 Diabetes Mellitus patients, demonstrated dapagliflozin's superiority over placebo in reducing hospitalization for heart failure/cardiovascular death and renal composite events, while showing non-inferiority for MACE. It also reduced new onset and progression of albuminuria. Safety analysis revealed balanced rates of overall serious adverse events and deaths, but higher rates of genital infections and diabetic ketoacidosis with dapagliflozin. Conversely, it showed lower rates of renal events and major hypoglycemic events. Additional analyses confirmed a consistent safety profile across subgroups. The variation led to updated product information, including a revised T2DM indication and inclusion of cardiovascular and renal benefits in the SmPC.
Key findings — cited to the page
| XIGDUO FDC EU approval date | 16 January 2014 | XIGDUO · EU · p.7 |
| EBYMECT FDC EU approval date | 16 November 2015 | EBYMECT · EU · p.7 |
| Type II variation application date | 8 January 2019 | · p.5 |
| Trial phase | Phase IIIb | D1693C00001/DECLARE-TIMI 58 · p.7 |
| Dapagliflozin dose | 10 mg | DECLARE · p.10 |
| Predicted median duration of treatment period | 4.5 years | DECLARE · p.10 |
| Primary events required for MACE superiority | 1390 | DECLARE · p.11 |
| Power to demonstrate MACE superiority | 85 % | DECLARE · p.11 |
| Assumed HR for MACE superiority | 0.85 | DECLARE · p.11 |
| One-sided alpha for MACE superiority | 2.31 % | DECLARE · p.12 |
| Randomised patients required for MACE superiority | 17150 | DECLARE · p.12 |
| Dapagliflozin EU approval date (FORXIGA) | November 2012 | FORXIGA · EU · p.7 |
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 →