Oral Garenoxacin in the Treatment of Acute Bacterial Maxillary Sinusitis: A Phase II, Multicenter, Noncomparative, Open-Label Study in Adult Patients Undergoing Sinus Aspiration

Abstract

Background: Garenoxacin is a des-F(6)-quinolone with in vitro activity against key respiratory pathogens, including Streptococcus pneumoniae, Hemophilus influenzae, Staphylococcus aureus, and Moraxella catar-rhalis. Limited data are available regarding the effect of garenoxacin in the treatment of acute bacterial sinusitis. Objective: The aim of this study was to assess the efficacy and tolerability of garenoxacin in adults with acute bacterial maxillary sinusitis undergoing a pre-treatment diagnostic sinus aspirate. Methods: This Phase II, multicenter, noncomparative, open-label study was conducted at 30 centers in the United States, Mexico, Argentina, and Europe. Male and female patients aged 18 to 80 years with clinical signs and symptoms lasting ≥5 but ⩽ 28 days and radiologic signs (air-fluid level, opacification, mucosal thickening) of acute maxillary sinusitis were eligible. The entry criteria for the 5-day treatment regimen did not include mucosal thickening of ≥5 mm because it was believed that improvement in mucosal thickening might not be reliably measurable at the 5-day time point. All patients received garenoxacin 400 mg QD for 5 or 10 days. Maxillary sinus needle aspiration for Gram stain, routine culture, and susceptibility testing were performed before treatment, and, if clinically indicated, during and after treatment. Bacteriologic eradication (negative culture on repeat sinus aspiration) and cure rates (complete resolution of all signs and symptoms) were assessed at a test-of-cure visit 5 to 18 days after the end of treatment. The occurrence of adverse events was recorded by the investigators up to 30 days after the last administration of garenoxacin by questioning patients. Results: A total of 546 patients were enrolled and 543 were randomized (5-day cohort: mean age, 40 years; mean weight, 76 kg; 56% women; 10-day cohort: mean age, 41 years; mean weight, 77 kg; 58% women). Clinically evaluable patients included 253 in the 5-day cohort and 266 in the 10-day cohort. Cure rates were 93% (236/253; 95% CI, 89%–96%) and 91% (243/266; 95% CI, 87%–94%) for evaluable patients in the 5− and 10-day cohorts, respectively. Bacteriologic eradication rates in microbiologically evaluable patients were 94% in both cohorts (5 days, 204/217; 10 days, 182/193). Eradication rates in the 5− and 10-day cohorts were as follows: S pneumoniae, 94% (62/66) and 93% (39/42); H influenzae, 100% (30/30) and 93% (26/28); S aureus, 96% (23/24) and 91% (31/34); and M catarrhalis, 89% (8/9) and 86% (12/14). Of the 9 patients with acute bacterial sinusitis due to multidrug-resistant S pneumoniae, 8 achieved clinical cure with garenoxacin treatment. Adverse events (AEs) most frequently reported were diarrhea (<2%), nausea (2%–6%), headache (2%–6%), and dizziness (<2%). Two percent of patients withdrew because of an AE (allergic reaction, adverse gastrointestinal effects, dyspnea, dizziness, headache, or elevation in liver enzymes). Conclusion: In this population of patients with signs and symptoms of acute maxillary sinusitis, oral garenoxacin 400 mg QD for 5 or 10 days eradicated 94% of bacterial pathogens associated with acute bacterial sinusitis in this population and appeared to be well tolerated in adults.