PMID- 25611308
OWN - NLM
STAT- MEDLINE
DCOM- 20151030
LR  - 20151119
IS  - 1755-3768 (Electronic)
IS  - 1755-375X (Linking)
VI  - 93
IP  - 4
DP  - 2015 Jun
TI  - A randomized phase I clinical study of cis-urocanic acid eye drops in healthy 
      adult subjects.
PG  - 368-76
LID - 10.1111/aos.12651 [doi]
AB  - 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 mug/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.
CI  - (c) 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & 
      Sons Ltd.
FAU - Jauhonen, Hanna-Mari
AU  - Jauhonen HM
AD  - Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
AD  - Department of Ophthalmology, Institute of Clinical Medicine, University of 
      Eastern Finland, Kuopio, Finland.
FAU - Kari, Eeva
AU  - Kari E
AD  - Laurantis Pharma Ltd, Turku, Finland.
FAU - Pylkkanen, Liisa
AU  - Pylkkanen L
AD  - Laurantis Pharma Ltd, Turku, Finland.
AD  - Cancer Society of Finland, Helsinki, Finland.
FAU - Poutanen, Jutta
AU  - Poutanen J
AD  - Laurantis Pharma Ltd, Turku, Finland.
FAU - Laihia, Jarmo
AU  - Laihia J
AD  - Laurantis Pharma Ltd, Turku, Finland.
FAU - Kaarniranta, Kai
AU  - Kaarniranta K
AD  - Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
AD  - Department of Ophthalmology, Institute of Clinical Medicine, University of 
      Eastern Finland, Kuopio, Finland.
FAU - Leino, Lasse
AU  - Leino L
AD  - Laurantis Pharma Ltd, Turku, Finland.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20150121
PL  - England
TA  - Acta Ophthalmol
JT  - Acta ophthalmologica
JID - 101468102
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Ophthalmic Solutions)
RN  - G8D26XJJ3B (Urocanic Acid)
SB  - IM
MH  - Administration, Topical
MH  - Adult
MH  - Anti-Inflammatory Agents, Non-Steroidal/*adverse effects/*pharmacokinetics
MH  - Biological Availability
MH  - Double-Blind Method
MH  - Eye/drug effects/metabolism
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Ophthalmic Solutions
MH  - Surveys and Questionnaires
MH  - Urocanic Acid/*adverse effects/*pharmacokinetics
MH  - Young Adult
OTO - NOTNLM
OT  - cis-UCA
OT  - clinical study
OT  - inflammatory ocular surface disease
OT  - ocular topical treatment
EDAT- 2015/01/23 06:00
MHDA- 2015/10/31 06:00
CRDT- 2015/01/23 06:00
PHST- 2014/06/17 00:00 [received]
PHST- 2014/11/30 00:00 [accepted]
PHST- 2015/01/23 06:00 [entrez]
PHST- 2015/01/23 06:00 [pubmed]
PHST- 2015/10/31 06:00 [medline]
AID - 10.1111/aos.12651 [doi]
PST - ppublish
SO  - Acta Ophthalmol. 2015 Jun;93(4):368-76. doi: 10.1111/aos.12651. Epub 2015 Jan 21.