Abstract
Purpose :
To investigate the effect of netarsudil ophthalmic solution 0.02% (AR-13324, a Rho Kinase and norepinephrine transporter inhibitor) on aqueous humor dynamics (AHD) including trabecular outflow facility, episcleral venous pressure (EVP) and intraocular pressure (IOP) in subjects with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).
Methods :
In this double-masked, vehicle-controlled, paired-comparison study conducted at 2 centers in the US, subjects (age ≥18 years) with POAG or OHT were randomized to netarsudil 0.02% in the study eye and vehicle in the contralateral eye each morning for 7 days. At baseline, both eyes required post-washout (4 weeks minimum)/treatment-naive IOP of >20 mmHg but <30 mmHg at 08:00. Outflow facility was measured by Schiøtz tonography. IOP was measured by pneumatonometry. EVP was measured using an objective, computer-controlled venomanometer and image analysis software. The primary endpoint was change from baseline in mean diurnal trabecular outflow facility (measurements at 13:00 and 16:00) on Day 8. Comparisons were performed and confidence intervals were calculated using paired t-tests.
Results :
Among 20 enrolled subjects (mean age 63 years), 18 were in the modified intent to treat population. Netarsudil increased mean diurnal trabecular outflow facility by 0.04 ± 0.04 µL/min/mmHg (mean ± SD) vs baseline, P=0.0004 (mean 34.6%) and 0.03 µL/min/mmHg vs vehicle-treated contralateral eyes, P=0.0010 (mean 25.0%). Netarsudil reduced mean diurnal IOP by 4.5 ± 1.6 mmHg vs baseline, P<0.0001 (mean -19.6%) and 3.5 mmHg vs vehicle, P<0.0001 (mean -15.3%). Mean diurnal EVP was reduced by 0.8 ± 0.8 mmHg vs baseline, P=0.0113 (mean -9.5%) and 0.9 mmHg vs vehicle, P=0.0003 (mean -12.6%). Adverse Events were reported in the study eyes of 13 subjects (65.0%) and were mild or moderate; none were serious. One subject discontinued due to mild conjunctival hyperemia.
Conclusions :
In the patient population studied, once-daily dosing of netarsudil 0.02% lowered IOP in subjects with POAG or OHT by improving outflow facility and reducing EVP. These results suggest netarsudil acts on the conventional outflow pathway including the distal outflow system, a novel mechanism of action among glaucoma medications.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.