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Acta Ophthalmol. 2015 Jun;93(4):368-76. doi: 10.1111/aos.12651. Epub 2015 Jan 21.

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

Author information

1
Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
2
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
3
Laurantis Pharma Ltd, Turku, Finland.
4
Cancer Society of Finland, Helsinki, Finland.

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.

KEYWORDS:

cis-UCA; clinical study; inflammatory ocular surface disease; ocular topical treatment

PMID:
25611308
DOI:
10.1111/aos.12651
[Indexed for MEDLINE]
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