A randomized phase i clinical study of cis-urocanic acid eye drops in healthy adult subjects

Abstract

Purpose To evaluate safety, ocular tolerability and pharmacokinetics of 0.5% and 2.5% cis-urocanic acid (cis-UCA) eye drops. Methods In this phase I, double-blinded, placebo-controlled trial, 37 healthy volunteers were randomized to three treatment arms: 0.5% cis-UCA (12 subjects), 2.5% cis-UCA (12 subjects) and placebo eye drops (13 subjects). In the first part, the subjects were dosed topically on a randomized eye with one drop three times at 7 ± 1 hr intervals during 1 day. In the second part, the subjects self-administered three daily drops at 7 ± 1 hr intervals on both eyes for 14 days. Physical examination of the eyes was performed seven times during the study. Tolerability of cis-UCA was assessed by ocular comfort rating questionnaire. Pharmacokinetic blood and urine samples were analysed under good laboratory practice (GLP). Results All subjects completed both parts of the study. There were no significant adverse events (AEs). The most common treatment-related ocular AE was eye irritation (62.2% of subjects). Cis-UCA concentrations in plasma remained below the limit of quantification (0.195 μg/ml) in all but two subjects. The fraction of the administered drug excreted into urine over the total collection period ranged from 3.2% to 61.6% of the last dose and from 1.1% to 20.5% of the daily dose. Conclusions Topical ocular administration of cis-UCA solution is safe and apart from mild- and short-lasting eye irritation after administration well tolerated in healthy adult subjects. Topical ocular dosing leads to transient systemic exposure to cis-UCA that does not cause systemic AEs.