title: A randomized phase I clinical study of cis-urocanic acid eye drops in healthy adult subjects.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.|Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Hanna-Mari
authors.initials: HM
authors.lastname: Jauhonen
authors.affiliation: Laurantis Pharma Ltd, Turku, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Kari
authors.affiliation: Laurantis Pharma Ltd, Turku, Finland.|Cancer Society of Finland, Helsinki, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Pylkkänen
authors.affiliation: Laurantis Pharma Ltd, Turku, Finland.
authors.forename: Jutta
authors.initials: J
authors.lastname: Poutanen
authors.affiliation: Laurantis Pharma Ltd, Turku, Finland.
authors.forename: Jarmo
authors.initials: J
authors.lastname: Laihia
authors.affiliation: Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.|Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
authors.affiliation: Laurantis Pharma Ltd, Turku, Finland.
authors.forename: Lasse
authors.initials: L
authors.lastname: Leino
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001682:Biological Availability; D004311:Double-Blind Method; D005123:Eye / Q000187:drug effects / Q000378:metabolism; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011795:Surveys and Questionnaires; D014560:Urocanic Acid / Q000009:adverse effects* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009883:Ophthalmic Solutions; D014560:Urocanic Acid
keywords: cis-UCA; clinical study; inflammatory ocular surface disease; ocular topical treatment