BACKGROUND/AIMS: To evaluate the ocular hypotensive efficacy, ocular and systemic safety, and systemic exposure of two formulations of 0.5% AR-12286 Ophthalmic Solution. METHODS: This was a double-masked, single-centre, crossover study in 18 normal adult volunteers. Volunteers were randomised to one of two dosing sequences: Formulation A once daily, both eyes (OU) for 8 days, a 7-day minimum washout, and then Formulation B, or the reverse. The main outcome measures were ocular tolerability, intraocular pressure (IOP) and blood levels of AR-12286 and its metabolites. RESULTS:Systemic absorption was low, with a majority of subjects showing no measurable drug concentration in plasma (<1 ng/ml) at any time point with either formulation. The most frequent ocular adverse events were conjunctival hyperaemia, eye irritation, instillation site reaction, increased lacrimation, and blurred vision which were relatively short-lived and judged as not clinically significant. Both formulations of AR-12286 produced substantial reductions from baseline IOP ranging from 3 to 7 mm Hg (p<0.0001). CONCLUSIONS: No differences were noted in ocular safety between formulations of AR-12286 0.5%, dosed once daily in the morning for 8 days. AR-12286 produced little systemic exposure to the parent compound or two known metabolites. Clinically and statistically significant reductions in IOP were seen in these normotensive subjects.
RCT Entities:
BACKGROUND/AIMS: To evaluate the ocular hypotensive efficacy, ocular and systemic safety, and systemic exposure of two formulations of 0.5% AR-12286 Ophthalmic Solution. METHODS: This was a double-masked, single-centre, crossover study in 18 normal adult volunteers. Volunteers were randomised to one of two dosing sequences: Formulation A once daily, both eyes (OU) for 8 days, a 7-day minimum washout, and then Formulation B, or the reverse. The main outcome measures were ocular tolerability, intraocular pressure (IOP) and blood levels of AR-12286 and its metabolites. RESULTS: Systemic absorption was low, with a majority of subjects showing no measurable drug concentration in plasma (<1 ng/ml) at any time point with either formulation. The most frequent ocular adverse events were conjunctival hyperaemia, eye irritation, instillation site reaction, increased lacrimation, and blurred vision which were relatively short-lived and judged as not clinically significant. Both formulations of AR-12286 produced substantial reductions from baseline IOP ranging from 3 to 7 mm Hg (p<0.0001). CONCLUSIONS: No differences were noted in ocular safety between formulations of AR-12286 0.5%, dosed once daily in the morning for 8 days. AR-12286 produced little systemic exposure to the parent compound or two known metabolites. Clinically and statistically significant reductions in IOP were seen in these normotensive subjects.
Authors: Guorong Li; Sina Farsiu; Stephanie J Chiu; Pedro Gonzalez; Elke Lütjen-Drecoll; Darryl R Overby; W Daniel Stamer Journal: Invest Ophthalmol Vis Sci Date: 2014-03-04 Impact factor: 4.799
Authors: Cheng-Wen Lin; Bryan Sherman; Lori A Moore; Carmen L Laethem; Da-Wen Lu; Padmanabhan P Pattabiraman; Ponugoti Vasantha Rao; Mitchell A deLong; Casey C Kopczynski Journal: J Ocul Pharmacol Ther Date: 2017-06-13 Impact factor: 2.671
Authors: Zeynep Aktas; Hongyu Rao; Sarah R Slauson; B'Ann T Gabelt; Inna V Larsen; Rachael T C Sheridan; Leonie Herrnberger; Ernst R Tamm; Paul L Kaufman; Curtis R Brandt Journal: Invest Ophthalmol Vis Sci Date: 2018-01-01 Impact factor: 4.799