Cis‐urocanic acid eye drops are safe and well tolerated in healthy adults – results from a randomised phase 1 clinical study

Abstract

Purpose Cis‐urocanic acid (cis‐UCA) is an endogenous small molecule of the skin. Preclinical data suggest that topical cis‐UCA could be used as an anti‐inflammatory treatment in ophthalmology. We investigated the safety, tolerability and pharmacokinetics (PK) of cis‐UCA in healthy adults in a randomised, double‐blind and placebo‐controlled phase 1 study. Methods The 37 subjects in 3 groups received either 0.5% or 2.5% cis‐UCA eye drops, or placebo. In part I, the eye drops were administered on one eye 3x in one day. In part II, the same subjects received the same eye drops on both eyes 3x a day for 14 days. Clinical evaluations included complete physical examination and safety laboratory tests, physical examination of the eyes, and ocular comfort rating by 5 parameters. Results Both cis‐UCA eye drops were safe and well tolerated throughout the study. None of the ocular safety parameters differed between cis‐UCA and placebo. Of the ocular comfort rating, only burning of the eyes was significantly higher with cis‐UCA than with placebo; however, this reaction was mild, transient and infrequent in all cases. PK analysis showed that 2.5% cis‐UCA eye drops may be absorbed after repeated ocular dosing, as 7/12 subjects in this group had low cis‐UCA levels (< 10 µg/ml) in the urine. However, plasma cis‐UCA levels were negligible. Conclusion The observed good local and systemic safety and tolerability of cis‐UCA eye drops warrants further clinical studies in patients with inflammatory ocular diseases. Commercial interest

Immunomodulation on the ocular surface: a review

“…The study confirmed potential having detectable (below 10 µg/ml) urine cis-UCA concentrations. However, its plasma concentrations were insignificant and negligible [ 72 ].…”