Integrated safety summary of CANVAS 1 and 2 trials: Phase III, randomized, double-blind studies evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections

Treatment of complicated skin and skin structure infections (cSSSIs) requires therapy that is effective against a range of Gram-positive and Gram-negative bacteria, including resistant pathogens such as methicillin-resistant Staphylococcus aureus. Equally important is the need to provide therapy that is safe and well tolerated. Ceftaroline fosamil is a new-generation, parenteral cephalosporin that was developed for the treatment of moderate to severe bacterial infections, including cSSSIs. This report provides an integrated safety summary of the CeftAroliNe Versus VAncomycin in Skin and Skin Structure Infections (CANVAS) 1 and 2 studies (registration numbers NCT00424190 and NCT00423657). Adult patients with cSSSIs requiring intravenous therapy received 600 mg of ceftaroline fosamil every 12 h or 1 g of vancomycin plus 1 g of aztreonam every 12 h for 5-14 days (randomized 1 : 1). All patients were followed for treatment-emergent adverse events (TEAEs) occurring from the start of the initial study drug infusion up to the test-of-cure visit, similar to 1 week following the last dose of study medication; serious adverse events (SAEs) that occurred within 30 days after the last dose were recorded. A total of 1378 patients received any amount of study drug and were included in the safety analysis. The percentage of patients with an SAE was similar between the ceftaroline fosamil and the vancomycin plus aztreonam groups (4.3% versus 4.1%). The majority of patients (> 75%) had either no or mild TEAEs and the distribution of TEAEs based on severity was comparable between the groups. The most commonly reported TEAEs in patients treated with ceftaroline fosamil included nausea (5.9%), headache (5.2%), diarrhoea (4.9%) and pruritus (3.5%). Ceftaroline fosamil was well tolerated and did not result in any unexpected safety concerns. The data from the CANVAS trials suggest that ceftaroline fosamil has the expected safety and tolerability profile common to the cephalosporin class.