Take-home message: Once-daily dosing of one drop of Roclatan (Aerie Pharmaceuticals, Inc.), containing a fixed-dose combination of latanoprost and a rho kinase inhibitor and norepinephrine transport inhibitor, was clinically and statistically superior to administration of its individual components for controlling IOP in open-angle glaucoma or ocular hypertension.
By Lynda Charters; Reviewed by Richard A. Lewis, MD
Sacramento, CA â Once-daily dosing of a single drop of a glaucoma drug (Roclatan, Aerie Pharmaceuticals, Inc.) containing a fixed-dose combination of latanoprost and a rho kinase inhibitor and norepinephrine transport inhibitor (Rhopressa) (Aerie Pharmaceuticals, Inc.) was found to be clinically and statistically superior to its individual components for controlling IOP in patients with open-angle glaucoma or ocular hypertension.
Dr. LewisThe PG324-CS201 Study Group conducted a double-masked, randomized, parallel comparison study with four treatment arms in which patients were randomly assigned to the rho kinase inhibitor and norepinephrine transport inhibitor (AR-13324) combined with latanoprost ophthalmic solution (PG324 0.01% or 0.02%) and compared with patients treated with AR-13324 0.02% or latanoprost ophthalmic solution 0.005%. The patients were treated for 28 days following a washout period. The primary endpoint was the mean diurnal IOP on day 29.
A total of 298 patients underwent the randomization phase and 292 completed the final evaluation. In the six patients who did not complete the study, one each developed a corneal ulcer resulting from latanoprost treatment, superficial punctuate keratitis, and subconjunctival hemorrhage; and one each withdrew consent, had a protocol violation, and disallowed concurrent medication.
Richard A. Lewis, MD, reported the study results on behalf of the PG324-CS201 Study Group. The mean untreated diurnal IOPs at the start of the study were 25.1 in both the PG324 0.01% and 0.02% groups, 26.0 in the latanoprost group, and 25.4 mm Hg in the AR-13324 group.
When the IOPs were measured on day 29, the respective results were 17.3, 16.5, 18.4, and 19.1 mm Hg, according to Dr. Lewis, who is in private practice in Sacramento, CA.
“The PG324 0.02% formulation met the criterion for statistically superiority compared with latanoprost and AR-13324 0.02% (P<0.0001), providing additional IOP lowering of 1.9 and 2.6 mm Hg, respectively,” Dr. Lewis said.
The other formulation, PG324 0.01% also was statistically superior compared with latanoprost and AR-13324, with additional IOP lowering of 1.1 and 1.8 mm Hg.
Conjunctival hyperemia was the most frequent adverse event associated with the fixed-dose combination drug in 41% and 40% of patients randomly assigned to the PG324 0.01% and 0.02% groups, respectively, and in 14% and 40% in the latanoprost and AR-13324 0.02% groups, respectively. According to the investigators, most of these events were mild and transient.
The authors concluded, “In this short-term study, the fixed-dose combination of AR-13324 0.02% and latanoprost 0.005% in the PG324 Ophthalmic Solution provides clinically and statistically superior ocular hypotensive efficacy relative to its individual active components at the same concentrations.”
The advantage to patients of such a combination drug is that it eliminates the need for them to instill multiple drugs over the course of a day in order to reach the target IOP. Multiple drugs may increase patient noncompliance with the regimen, especially in an elderly population. Administration of two drugs once daily may increase patient compliance.
The investigators reported their results in the British Journal of Ophthalmology.
Richard A. Lewis, MD
Dr. Lewis is a consultant for Aerie Pharmaceuticals and holds stock in the company. Aerie Pharmaceuticals Inc. sponsored the study.