BARCELONA, Spain, May 12, 2014 /PRNewswire/ —
Phase III Data presented at 24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)
AstraZeneca has announced results from a Phase III comparator trial, which demonstrated ZINFORO™ (ceftaroline fosamil) 600mg twice daily is more effective compared to ceftriaxone 2g for treating Asian patients with community-acquired pneumonia (CAP). Results were presented today at the 24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Barcelona, Spain.
The primary objective of the Phase III, randomised, double-blind, active comparator trial (NCT01371838) was to assess the effectiveness of ceftaroline fosamil in adult patients with CAP in the Asian region, compared with cefriaxone. Safety and tolerability were secondary objectives. Results showed that ceftaroline fosamil demonstrated greater efficacy and comparable tolerability compared to ceftriaxone (clinical cure rates at the test-of-cure [TOC] visit in the clinically evaluable [CE] population were 84.1% for ceftaroline fosamil and 74.2% for ceftriaxone). Serious adverse events were uncommon and similar across the treatments.
“The results of this study are an exciting development for ZINFORO™, further demonstrating its suitability as an effective treatment option for vulnerable patients with CAP,” said David Melnick, VP Clinical Development, Infection Global Development, AstraZeneca. “This study is the third consecutive Phase III clinical trial in CAP demonstrating a strong response trend favouring ceftaroline over ceftriaxone (both 1 and 2g/day) adding to the overall body of ZINFORO™ data.”
The study included adult patients (number of study sites with ≥1 patient enrolled) from China (23), India (13), Korea (16), Taiwan (7), and Vietnam (5) with a diagnosis of CAP requiring hospitalisation and Pneumonia Outcomes Research Team (PORT) risk class III or IV who were randomised 1:1 to ceftaroline fosamil 600 mg q12h (n=385) or ceftriaxone 2 g q24h (n=386) for five to seven days between December 2011 and May 2013.
The primary objective of the study was to assess clinical cure rates at the TOC visit in the CE population; non-inferiority was defined as a lower limit of the 95% CI ≥ -10% for the between-group difference. If this was achieved, the protocol stated that superiority would be concluded if the lower limit of the 95% CI > 0%. Safety and tolerability were secondary objectives.
The study demonstrated that ceftaroline fosamil 600 mg q12h had greater efficacy compared to ceftriaxone 2 g q24h as treatment in Asian patients with PORT class III or IV CAP. The safety profile of ceftaroline fosamil was comparable to ceftriaxone, and as expected for the cephalosporin class. The between-group difference (95% CI) was 9.9% (2.8, 17.1), demonstrating the superiority of ceftaroline fosamil 600 mg q12h to ceftriaxone 2 g q24h. Similar efficacy results were observed in the modified intent-to-treat (MITT) and microbiologically-confirmed MITT populations, with the lower limit of the 95% CI exceeding 0% for the between-group difference.
In the safety population, 45.1% (172/381) of patients randomised to ceftaroline fosamil and 42.6% (163/383) of patients randomised to ceftriaxone experienced ≥1 adverse event (AE). The most common AEs were related to the gastrointestinal system. There were 24 (6.3%) vs 13 (3.4%) patients with diarrhoea and 18 (4.7%) patients vs 9 (2.3%) patients with constipation in the ceftaroline and ceftriaxone treatment arms respectively. The number of patients with serious adverse events were comparable in both treatment arms with 30 (7.9%) patients in the ceftaroline arm and 29 (7.6%) patients in the cetriaxone arm. Discontinuation due to adverse events were similar in both treatment arms 7 (1.8%) vs 7 (1.8%).
In the Asia-Pacific region, CAP remains an important cause of mortality and morbidity amongst adults, and contributes a significant health and economic burden.
The study complements two previous, successful, trials (the FOCUS -1 and -2 studies) which were conducted by Forest Laboratories Inc. in a largely Western population and formed the basis for marketing authorisation approval in the European Union (EU) in August 2012, and a number of other markets.
The study included patients with CAP from China, India, Korea, Taiwan, and Vietnam and will support regulatory submissions in China and other key Asian markets.
In 2009, Forest Laboratories Inc. granted AstraZeneca exclusive worldwide commercial rights and co-exclusive development rights for ceftaroline fosamil, excluding US, Canada and Japan. Forest launched ceftaroline fosamil with similar indications under the trade name Teflaro® in the US in March 2011.
About ZINFORO™
ZINFORO™ (ceftaroline fosamil) is an intravenous cephalosporin antibiotic intended for use as a monotherapy in the treatment of adult patients with complicated skin and soft tissue infections (cSSTI) or community-acquired pneumonia (CAP). ZINFORO™ is bactericidal and works by binding to and inhibiting penicillin-binding proteins (PBPs). PBPs are involved in bacterial cell wall synthesis and repair and their inhibition leads to reduced bacterial cell replication and/or cell death.
ZINFORO™ was granted Marketing Authorisation by the European Commission (EC) for the treatment of adult patients with cSSTI or CAP on 28 August, 2012.
About CAP
Community Acquired Pneumonia (CAP) is an acute infection of the lungs (pneumonia) in a patient who has not been exposed to a hospital or long-term care facility. The estimated annual incidence of CAP varies from five to 11 cases per 1,000 people, with the rates being higher in the elderly. In the Asia-Pacific region, CAP is an important cause of mortality and morbidity amongst adults, and a significant health and economic burden.
CAP is commonly associated with considerable morbidity, mortality, resource use and healthcare costs and, despite the availability of a number of antibiotics to treat CAP, studies show that many patients do not receive effective first-line empiric treatment. First-line treatment modification can be associated with significant clinical and economic consequences – including increased hospital stays, increased treatment costs and risk of mortality.
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: http://www.astrazeneca.com