title: Ocular safety of INS365 ophthalmic solution: a P2Y(2) agonist in healthy subjects.
abstract: The purpose of this study was to evaluate the ocular safety and tolerability of the P2Y(2) receptor agonist, INS365, when applied as eye drops in normal human subjects. This study was a double-masked, placebo-controlled, randomized, within subject paired-comparison, dose-escalation study in five cohorts of ten healthy subjects. The concentrations of INS365 ophthalmic solution were 0.5, 1.0, 2.0, and 5.0% given three times over six hours. Safety was assessed by general and ophthalmic examination and symptomatology. Unanesthetized Schirmer tests were performed in the last cohort of 10 subjects to evaluate the acute effects of INS365 on tear secretion. There were no significant differences in the number of subjects with ocular events reported in placebo-treated eyes compared to INS365-treated eyes. Two adverse events were possibly related to INS365: painless blepharospasm and an increase in lacrimation after 5.0% INS365 instillation. Unanesthetized Schirmer testing showed no acute effects of INS365 on tear secretion, compared to its vehicle, in healthy subjects, in which reflex tearing often produced maximal Schirmer values. INS365 ophthalmic solution was well-tolerated when administered by ocular instillation. Stimulation of ocular surface P2Y(2) receptors was not associated with ocular tolerability issues in healthy subjects.
authors.affiliation: Bristol Eye Hospital, United Kingdom.
authors.forename: M V
authors.initials: MV
authors.lastname: Mundasad
authors.forename: G D
authors.initials: GD
authors.lastname: Novack
authors.forename: V E
authors.initials: VE
authors.lastname: Allgood
authors.forename: R M
authors.initials: RM
authors.lastname: Evans
authors.forename: J C
authors.initials: JC
authors.lastname: Gorden
authors.forename: B R
authors.initials: BR
authors.lastname: Yerxa
mesh_terms: D000287:Administration, Topical; D000328:Adult; D015331:Cohort Studies; D004311:Double-Blind Method; D015352:Dry Eye Syndromes / Q000188:drug therapy; D005260:Female; D006801:Humans; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011122:Polyphosphates; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D012449:Safety; D013666:Tears / Q000378:metabolism; D014500:Uracil Nucleotides
chemical_list: D009077:Mucins; D009883:Ophthalmic Solutions; D011122:Polyphosphates; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D014500:Uracil Nucleotides; C403315:diquafosol