Ocular hypotensive efficacy and safety of a fixed dose combination of AR-12286 (a Rho Kinase Inhibitor) and travoprost

摘要

Purpose: Prostaglandin agonists (PGA) facilitate IOP lowering by enhancing uveoscleral outflow. ROCK inhibitors mechanistically lower IOP by enhancing trabecular outflow. For patient convenience, we developed a fixed dose combination (FDC) of a ROCK inhibitor (AR 12286, Williams RD, Novack GD, van Haarlem T, et al. Ocular hypotensive effect of the Rho kinase inhibitor AR-12286 in patients with glaucoma and ocular hypertension. Am J Ophthalmol 2011;152:834-41) and a PGA (travoprost). Methods: Two AR-12286 (0.25% and 0.5%)/ travoprost fixed-dose combination products (PG286) were compared to travoprost (Travatan?? Z) in 93 patients with elevated intraocular pressure in a double-masked, randomized, controlled study. All dosing was once-daily at night. Results: From a mean baseline IOP of 26.6 to 26.8 mm Hg, 16 hours after first dose, mean IOP was 17.7, 15.8 and 18.1 mmHg in the PG286-0.25%, PG286-0.5% and travoprost groups, respectively. This represented a mean decrease from diurnally adjusted baseline IOP of 8.9 (33%), 11.0 (41%) and 8.5 mmHg (32%), respectively. On day 7 at 08:00 hours, approximately 12 hours after the final dose, mean IOP was 17.5, 14.6 and 17.5 mmHg in the PG286-0.25%, PG286-0.5% and travoprost groups, respectively. This represented a mean decrease from diurnally adjusted baseline IOP of 9.2 (34%), 12.2 (46%), and 9.1 mmHg (34%). Mean IOP remained decreased throughout the day, with mean IOPs of 17.5, 15.0, and 17.1 mmHg, respectively at 16:00 hours. The additional IOP reduction achieved by PG286-0.5% compared to travoprost was statistically significant at each time point on Day 7. The most frequently reported events were mild to moderate conjunctival hyperemia, 32% (10/31), 59% (17/29) and 42% (14/33) in the PG286-0.25%, PG286-0.5% and travoprost groups, respectively. The incidence of conjunctival hyperemia of grade 2 or greater at Day 7 was 0%, 12% and 12%, respectively. Conclusions: Conclusion: The ocular hypotensive effect of PG286-0.5% was clinically and statistically greater than travoprost alone, with mean IOP less than 16 mm Hg at each time point. Hyperemia with PG286 was similar to travoprost alone. PG286, a ROCK/PGA fixed dose combination, was a highly effective ocular hypotensive treatment.