Fixed-dose combination of AR-13324 and latanoprost: a double-masked, 28-day, randomized, controlled study in patients with open-angle glaucoma or ocular hypertension
Richard A. Lewis1, Brian Levy2, Nancy Ramirez2, Casey C. Kopczynski2, Dale W. Usner3, Gary D. Novack4 for the PG324-CS201 Study Group
1Sacramento Eye Consultants, Sacramento, CA, USA
2Aerie Pharmaceuticals Inc., Bridgewater, NJ, USA & Research Triangle Park, NC, USA
3Statistics & Data Corporation (SDC), Tempe, AZ, USA
4PharmaLogic Development Inc., San Rafael, CA, USA
Tempe, AZ, August 24, 2015 – Dale W. Usner, Ph.D., President of SDC, co-authored the publication “Fixed-dose combination of AR-13324 and latanoprost: a double-masked, 28-day, randomized, controlled study in patients with open-angle glaucoma or ocular hypertension,” first published online in the British Journal of Ophthalmology on July 24, 2015. “Fixed-dose combination of AR-13324 and latanoprost: a double-masked, 28-day, randomized, controlled study in patients with open-angle glaucoma or ocular hypertension” details the background, methods, results, and conclusions from the corresponding study of AR-13324 ophthalmic solution in patients with glaucoma or ocular hypertension. The data support the conclusion that “the fixed-dose combination of AR-13324 0.02% and latanoprost 0.005% in PG324 Ophthalmic Solution provides clinically and statistically superior ocular hypotensive efficacy relative to its individual active components at the same concentrations.” For more information about this study, please download the full publication online from the British Journal of Ophthalmology or visit clinicaltrials.gov.
Abstract
Background/aims
To evaluate the ocular hypotensive efficacy of fixed-dose combinations of the Rho kinase inhibitor and norepinephrine transport inhibitor AR-13324 (0.01% and 0.02%) and latanoprost (PG324 Ophthalmic Solution) relative to the active components AR-13324 0.02% and latanoprost 0.005%, used bilaterally at night.
Methods
This was a double-masked, randomized, parallel comparison study in patients with open-angle glaucoma or ocular hypertension. After washout, patients were randomized to one of four treatment arms and treated for 28 days. The primary efficacy variable was mean diurnal intraocular pressure (IOP) at day 29.
Results
298 patients were randomized, of whom 292 (98%) completed the study. Mean unmedicated diurnal IOPs (study eye) was 25.1, 25.1, 26.0 and 25.4 in the PG324 0.01%, PG324 0.02%, latanoprost and AR-13324 0.02% groups, respectively. On day 29, mean diurnal IOP decreased to 17.3, 16.5, 18.4 and 19.1 mm Hg, respectively. For the primary efficacy variable of mean diurnal IOP at day 29, PG324 0.02% met the criterion for statistical superiority relative to both latanoprost and AR-13324 0.02% (p<0.0001), providing additional IOP lowering of 1.9 and 2.6 mm Hg, respectively. PG324 0.01% also met the criterion for superiority. The most frequently reported adverse event was conjunctival hyperemia with an incidence of 41% (30/73), 40% (29/73), 14% (10/73) and 40% (31/78) in the PG324 0.01%, PG324 0.02%, latanoprost and AR-13324 0.02% groups, respectively. Conclusions
In this short-term study, the fixed-dose combination of AR-13324 0.02% and latanoprost 0.005% in PG324 Ophthalmic Solution provides clinically and statistically superior ocular hypotensive efficacy relative to its individual active components at the same concentrations. The only safety finding of note was transient asymptomatic conjunctival hyperemia which was typically of mild severity.
About Dale W. Usner, Ph.D.
Dr. Usner has approximately 20 years of experience leading and executing clinical trial research, including over a decade in ophthalmic pharmaceuticals and devices. Joining SDC in September 2011, Dale has since served the company in various positions of increasing responsibility, including most recently as Vice President of Biostatistics & Data Management and currently as President. Prior to his position with SDC, he worked at AVI BioPharma and ZymoGenetics as the head of statistics and data management, at Bausch & Lomb, Inc. as the global head of statistics and data management, and at PPD, Inc. He maintains an array of therapeutic area expertise, including anti-viral/anti-infective, oncology, ophthalmic device, ophthalmic pharmaceuticals, and gastrointestinal. Dale also has a breadth of regulatory body meeting experience with the FDA, PMDA, and EMA, including involvement in advisory committee meetings. Dale holds a Ph.D. in Statistics from Oregon State University.
