Urinary tract infection agent yields positive phase III study results

Ceftolozane/tazobactam, an investigational antibiotic, showed positive top-line results in a pivotal phase III clinical trial of the drug’s use in complicated urinary tract infections (cUTI), Cubist Pharmaceuticals, Inc. reported.

Ceftolozane/tazobactam met its primary endpoint of statistical non-inferiority compared to levofloxacin (Levaquin) (10% non-inferiority margin). The primary endpoint is a composite of microbiologic eradication and clinical cure rate (composite cure rate) at 5 to 9 days after end of therapy (the test of cure visit). The 95% confidence interval around the treatment difference had lower and upper bounds of 2.3% and 14.6%, respectively, favoring ceftolozane/tazobactam, Cubist said in a release. Results of the secondary analyses were consistent with and supportive of the primary outcome.

Although this trial was not prospectively designed to demonstrate superiority, the finding that the lower bound of the 95% confidence interval around the positive treatment differences in favor of ceftolozane/tazobactam was greater than zero indicated statistical superiority over levofloxacin in this trial.

The spectrum of gram-negative pathogens seen in this trial was typical of that seen in other clinical trials in patients with cUTI, the company said.

The treatment-emergent adverse event rate was 34.7% for ceftolozane/tazobactam and 34.4% for levofloxacin. The most commonly reported adverse events were headache (5.8%), constipation (3.9%), hypertension (3%), nausea (2.8%), and diarrhea (1.9%). This adverse event profile is consistent with that seen with ceftolozane/tazobactam in the prior phase II trial in cUTI and comparable to levofloxacin in this study.

“We are very pleased with these positive results, which represent a significant milestone for both ceftolozane/tazobactam and Cubist. As the global leader in antibiotic research and development, Cubist is committed to combating the growing threat of resistant bacteria and providing needed therapies for patients with serious infections,” said Steven Gilman, PhD, of Cubist Pharmaceuticals.

Cubist is also concluding a pivotal phase III trial of ceftolozane/tazobactam in patients with complicated intra-abdominal infections (cIAI). The company said it expects to announce cIAI top-line data later this month and, as previously agreed to with regulatory authorities, the cUTI and cIAI data together will form the potential submission package to regulatory authorities requesting approval in both indications.

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