Successful Phase-III studies of CAZ AVI for Intra-Abdominal Infections - AstraZeneca + Forest

AstraZeneca announced positive top-line results from RECLAIM-1 and RECLAIM-2 , the pivotal Phase III studies investigating the potential of the antibiotic ceftazidime-avibactam (CAZ-AVI) as a treatment for hospitalised adult patients with complicated Intra-Abdominal Infections. CAZ-AVI consists of a cephalosporin (ceftazidime), an established treatment for serious bacterial infections, and a next generation non-beta lactam beta-lactamase inhibitor (avibactam). CAZ-AVI is being developed to treat a broad range of Gram-negative bacterial infections which are becoming resistant to antibiotics and pose an increasing threat to public health. The addition of avibactam protects ceftazidime from being broken down by beta-lactamases that are produced by resistant bacteria.

The global RECLAIM-1 and RECLAIM-2 Phase III studies both evaluated the safety and efficacy of CAZ-AVI, administered intravenously as a two hour infusion (2000 mg / 500 mg) plus metronidazole, compared to meropenem, administered intravenously as a 30 minute infusion (1 g), in hospitalised adult patients with complicated Intra-Abdominal Infections. Data from the RECLAIM-1 and RECLAIM-2 studies were analysed as a single-pooled dataset with the agreement of the FDA and the European Medicines Agency (EMA). In the RECLAIM-1 and RECLAIM-2 Phase III studies, CAZ-AVI met the objective of statistical non-inferiority compared to meropenem. The primary endpoint was a clinical cure rate 28 to 35 days after randomisation (the Test of Cure visit). CAZ-AVI also treated cIAI patients infected with ceftazidime-resistant bacteria as effectively as meropenem. The adverse event rate for CAZ-AVI in combination with metronidazole was similar to meropenem.