Efficacy and safety of 1.5% levofloxacin otic solution for the treatment of otitis media in a multicenter, randomized, double-blind, parallel-group, placebo-controlled, phase III study.

ABSTRACT

OBJECTIVE: The present study aimed to evaluate the efficacy and safety of 1.5% levofloxacin (LVFX) otic solution for the treatment of patients with otitis media. METHODS: This multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 trial was conducted at 34 institutions in Japan. A total of 202 patients with chronic suppurative otitis media (CSOM) or acute otitis media (AOM) were randomized into either the LVFX group or placebo group. A total of 6-10 drops of 1.5% otic solution of LVFX or its matching placebo were administered in the diseased ear twice daily, in the morning and evening for up to 10 days. Images corresponding to three clinical findings-purulent otorrhea, hyperemia (redness), and granulation tissue formation in the middle ear and tympanic membrane-for each diseased ear were evaluated using digital endoscopy by a blinded central independent review committee (BICRC) at each visit after treatment administration. RESULTS: In total, the data of 201 participants (LVFX group, 99; placebo group, 102) were analyzed. The proportion of patients with disappearance (improvement rate) of all three clinical findings at the end of treatment or discontinuation by the BICRC was 46.5% (46/99) in the LVFX group and 23.5% (24/102) in the placebo group, and the difference (95% confidence interval) between the groups was 22.0% (8.7, 34.2), with a significantly higher improvement rate in the LVFX group than in the placebo group (p = 0.001; Cochran-Mantel-Haenszel test), demonstrating the efficacy of LVFX. The bacterial eradication rates were 93.9% (77/82) and 12.5% (11/88) in the LVFX and placebo groups, respectively, and the rate was significantly higher in the LVFX group than in the placebo group (p < 0.001). Treatment-related adverse events (AEs) occurred in 5.1% (5/99) and 7.8% (8/102) of the patients in the LVFX and placebo groups, respectively, and no significant difference was noted in incidence rate between the groups. CONCLUSION: The clinical efficacy of 1.5% LVFX otic solution for CSOM and AOM was demonstrated by the resolution of inflammation in the middle ear and tympanic membrane as well as through the high bacterial eradication rate observed. No deaths or serious treatment-related AEs were observed. The study provided confirmation that 1.5% LVFX otic solution is a safe, well-tolerated, and effective treatment for CSOM and AOM.