Clinical phase 1 safety and tolerability evaluation of sustained release silica composite eye drops in human subjects

Abstract

Aims/Purpose: Most ocular disease is managed at least in part by use of eye drops. Many of these eye drops require multiple doses per day, as well as good patient compliance to relieve patients from incapacitating symptoms. To address this treatment burden, a Silica Matrix long‐acting eye drop technology was developed to offer a once‐a‐day (QD) dosing schedule. The aim of this study was to evaluate safety and tolerability of QD repeated dosing of silica composite eye drop platform in healthy volunteers for 15 days.Methods: 24 healthy volunteers were recruited to a randomized, double blinded, placebo‐controlled phase 1 clinical trial for repeated, QD dosing of silica composite eye drops over 15 days. Half of the subjects received a demulcent containing silica composite eye drops and the other half received plain silica composite eye drops (i.e., placebo). A single drop was applied QD in the cul‐de‐sac of one eye, and safety and tolerability was assessed by a blinded Investigator, including examination of outer eye structures and anterior chamber as well as interblink interval and tear fluid break‐up time (t0, 6h, D2, D3, D7, D11 and D15), lens examination (microscopic), change in visual acuity (EDTRS) and intra‐ocular pressure (t0 and D15). Ocular discomfort was assessed by volunteer questionnaire at t0, 6h, D3, D7, D11 and D15.Results: At submission, 13 subjects have completed the study and 11 are still under investigation. No significant differences in tolerability were observed between treated and untreated eyes, with no relevant adverse events. Volunteer questionnaire results indicate that 71% regarded instillation discomfort as mild, 22% moderate and 7% had no symptoms. Discomfort lasted less than 1‐min in 99% of responses.Conclusions: The results indicate that silica composite eye drops are safe and well tolerated in healthy volunteers when applied QD. This forms a good basis for development of sustained release topical ocular products for delivery of pharmacologically active agents in eye diseases.