US-based biopharmaceutical firm Cubist Pharmaceuticals has released positive top-line results from its Phase III clinical trial of an antibiotic candidate ceftolozane/tazobactam for the treatment of complicated intra-abdominal infections (cIAI).
Compared to meropenem, ceftolozane/tazobactam in combination with metronidazole, met the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) defined primary endpoints of statistical non-inferiority.
Primary endpoint of the trial was a clinical cure rate 26-30 days after the start of therapy (the test of cure visit).
For the FDA, the primary analysis was carried out in the microbiological intent-to-treat (MITT) population; the non-inferiority margin was 10%; and the lower and upper bounds of the 95% confidence interval were -8.9% and 0.5%, respectively.
Primary analysis population for the EMA was clinically evaluable (CE) patients; the non-inferiority margin was 12.5%; and the lower and upper bounds of the 99% confidence interval were -4.2% and 4.3%, respectively.
According to the company, results of the secondary analysis were consistent with and supportive of the primary outcome.
In the trial, treatment emergent adverse event rate for ceftolozane/tazobactam in combination with metronidazole, was 44% and for meropenem was 42.7%, while the most commonly reported adverse events were nausea (7.9%), diarrhea (6.2%), fever (5.2%), insomnia (3.5%), and vomiting (3.3%).
Most common Gram-negative pathogens seen in the cIAI trial included Escherichia coli (E coli), Klebsiella pneumoniae (K. pneumoniae) and Pseudomonas aeruginosa (P. aeruginosa).
The cIAI trial results follow the positive data from a Phase III trial of ceftolozane/tazobactam compared to levofloxacin in patients with complicated urinary tract infections (cUTI).
Cubist Pharmaceuticals executive vice-president of research and development and chief scientific officer Steven Gilman said: "With positive results from Phase 3 clinical trials of ceftolozane/tazobactam in both cUTI and cIAI, we look forward to submitting these data to global regulatory authorities and presenting the full results at upcoming medical meetings."
Based on the cUTI and cIAI trials, the company intends to file a new drug application (NDA) to the FDA in the first half of 2014 for approval in both of these indications as well as submit a marketing authorisation application to the EMA in the second half of 2014.
Ceftolozane/tazobactam, an antibiotic candidate being developed to treat certain Gram-negative infections, consists of ceftolozane, a novel cephalosporin, and tazobactam, a well-established ß-lactamase inhibitor.
It is currently being developed for the potential treatment of complicated urinary tract infections (cUTI) and cIAI.
Previously, Ceftolozane/tazobactam has received Qualified Infectious Disease Product designation, following which, it later also secured the FDA Fast Track status.
Image: Microscopic image of Pseudomonas aeruginosa. Photo: courtesy of Y tambe.