The Safety of Besifloxacin Ophthalmic Suspension 0

Authors: Ranjan Malhotra Stacey Ackerman Lynne S Gearinger Timothy W Morris Catherine Allaire

Publish Date: 2013/10/19

Volume: 13, Issue: 4, Pages: 243-252

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Abstract

This randomized multicenter doublemasked vehiclecontrolled parallelgroup study involved 518 patients ≥1 year of age with a clinical diagnosis of bacterial conjunctivitis Patients were randomized 21 to treatment with besifloxacin 06  ophthalmic suspension or vehicle one drop in the infected eyes TID for 7 days Main outcomes included the incidence and types of adverse events reported by the subject or observed by the investigator at each study visitThirtyone ocular treatmentemergent adverse events TEAEs were reported by 28 subjects in the study eye 19 occurred in 17/344 49  besifloxacin patients and 12 occurred in 11/170 65  vehicle patients p = 05362 Only two ocular events mild instillation site reaction one case in each group were considered “definitely related” to study treatment One event of selflimited dysgeusia in the besifloxacin group was considered definitely related to treatment there were no other nonocular TEAEs considered related to treatment There were no serious adverse events and other safety outcomes visual acuity biomicroscopy ophthalmoscopy were unremarkableBesifloxacin ophthalmic suspension 06  Besivance™ Bausch Lomb Rochester NY USA was approved by the FDA in 2009 for the treatment of bacterial conjunctivitis 1 The marketed product is formulated with DuraSite® InSite Vision Inc Alameda CA USA a mucoadhesive polymer delivery system designed to prolong the drug’s residence time on the ocular surface and facilitate longacting topical antibacterial activity 2 3 4 5 Besifloxacin is an 8chlorofluoroquinolone that has an R7aminoazepinyl group with broad spectrum in vitro activity against a wide range of Grampositive and Gramnegative ocular pathogens including multidrugresistant strains 6 7 8 9 10 The mechanism of action of besifloxacin involves inhibition of bacterial DNA gyrase and topoisomerase IV enzymes which are essential for the synthesis and replication of bacterial DNA 11 12 Unlike older fluoroquinolones besifloxacin demonstrates relatively balanced activity against both DNA gyrase and topoisomerase IV this minimizes the likelihood of resistance which would require concomitant mutations in both enzymes 11 12Three large clinical trials have established the safety and efficacy of besifloxacin ophthalmic suspension 06  compared with vehicle 13 14 or active comparator moxifloxacin ophthalmic solution 05  15 when given three times a day for 5 days to treat acute bacterial conjunctivitis The FDA approved labeling for besifloxacin like most other topical ophthalmic antibacterials recommends a 7day treatment period for bacterial conjunctivitis 1 Because besifloxacin exposure in the efficacy studies was limited to 5 days the objective of this study was to compare safety outcomes associated with besifloxacin ophthalmic suspension 06  administered three times a day for 7 days with those reported with the use of vehicle aloneThis study was a multicenter randomized doublemasked vehiclecontrolled parallelgroup trial designed to evaluate the safety of besifloxacin ophthalmic suspension 06  compared to vehicle in patients with acute bacterial conjunctivitis The study involved 24 investigators at 24 sites across the United States The protocol was approved by the institutional review board at each facility and written informed consent was obtained for all subjects prior to enrollment For all subjects younger than 18 years of age signed consent was required of a legally authorized representative subjects between the ages of 6 and 17 years also cosigned the consent forms

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