AstraZeneca PLC — Komboglyze EMA EPAR public assessment report (EMEA/H/C/002059, 2011)
AstraZeneca PLC · 2011 · EMA EPAR public assessment report · company profile →
Report summary
The EMA's assessment of Komboglyze (saxagliptin/metformin) led to a positive CHMP opinion for marketing authorization in September 2011 for adults with type 2 diabetes. Non-clinical studies confirmed safety, and pharmacokinetic studies established bioequivalence of the fixed-dose combination. Phase 3 trials demonstrated significant HbA1c reductions with saxagliptin as monotherapy or in combination with metformin, showing acceptable efficacy against placebo and active comparators. The safety profile was generally comparable to individual components, with common adverse events and specific warnings for hypoglycemia, pancreatitis, and metformin-related lactic acidosis. While efficacy was established, safety in specific populations (pediatric, cardiovascular, pregnant/breastfeeding) remains unconfirmed. Overall, a positive benefit-risk balance was concluded.
Key findings — cited to the page
| Saxagliptin exposure in severe hepatic impairment (Child-Pugh Class C) | 1.8 -fold higher | · p.23 |
| BMS-510849 exposure in moderate hepatic impairment (Child-Pugh Class B) | 7 % lower | · p.23 |
| Study CV181054 saxagliptin dose | 5 mg | CV181054 · p.28 |
| Study CV181038 saxagliptin dose | 2.5 QAM, 5QAM, 2.5/5 QAM, 5 QPM, all titratable to 10 mg | CV181038 · p.28 |
| BMS-510849 exposure in mild hepatic impairment (Child-Pugh Class A) | 22 % lower | · p.23 |
| BMS-510849 exposure in moderate renal impairment (≥ 30 to ≤ 50 ml/min) | 2.9 -fold higher | · p.22 |
| BMS-510849 exposure in mild renal impairment (> 50 to ≤ 80 ml/min) | 1.7 -fold higher | · p.22 |
| BMS-510849 exposure in severe renal impairment (19-30 ml/min) | 4.5 -fold higher | · p.22 |
| Saxagliptin exposure in mild hepatic impairment (Child-Pugh Class A) | 1.1 -fold higher | · p.23 |
| Saxagliptin exposure in moderate hepatic impairment (Child-Pugh Class B) | 1.4 -fold higher | · p.23 |
| Study CV181056 duration | 18 weeks | CV181056 · p.28 |
| BMS-510849 exposure in severe hepatic impairment (Child-Pugh Class C) | 33 % lower | · p.23 |
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 →