A Randomized, Phase 2 Study of 24-h Efficacy and Tolerability of Netarsudil in Ocular Hypertension and Open-Angle Glaucoma

James H Peace, Hayley J McKee, Casey C Kopczynski, James H Peace, Hayley J McKee, Casey C Kopczynski

Abstract

Introduction: Pharmacotherapy to lower intraocular pressure (IOP) is a mainstay of treatment aimed at delaying progression of visual field loss in ocular hypertension (OHT) and open-angle glaucoma (OAG), but some topical treatments are less effective in controlling IOP at night. Peak IOP may be related to glaucoma progression and can occur outside office hours. A phase 2 study was conducted to evaluate the IOP-lowering efficacy of netarsudil across the diurnal and nocturnal periods.

Methods: This was a randomized, double-masked, single-center, vehicle-controlled, 9-day study. After washout of any prior ocular hypotensive agents, 12 patients with OHT or OAG underwent baseline IOP assessment at 15:00, 18:00, 21:00, 00:00, 03:00, 06:00, 09:00, and 12:00 h on day 1/day 2. Participants were then randomized in a 2:1 ratio to netarsudil ophthalmic solution 0.02% (n = 8) or vehicle (n = 4) for 7 days of self-administered dosing each evening. IOP was assessed at the same time points on day 8/day 9. All measurements were conducted with a Perkins tonometer in habitual positions by day (seated) and at night (supine).

Results: Baseline mean 24-h IOP was 22.4 mmHg in the netarsudil group and 22.9 mmHg in the vehicle group. Netarsudil was associated with a reduction in mean nocturnal IOP (measurements at 21:00, 00:00, 03:00, 06:00 h) of 3.5 mmHg, which was significant relative to baseline nocturnal IOP (P < 0.001) and the reduction in the vehicle group (0.4 mmHg; P < 0.001 vs. netarsudil). Reduction in mean diurnal IOP with netarsudil (3.5 mmHg) was the same as the nocturnal reduction and statistically significant versus baseline (P < 0.001) and the vehicle group (0.9 mmHg; P < 0.01). The magnitude of IOP reductions with netarsudil was consistent at each time point assessed over the 24-h period. No adverse events were reported.

Conclusion: Netarsudil exhibited consistent IOP-lowering efficacy over a 24-h period in this short-term study.

Trial registration: Clinicaltrials.gov identifier: NCT02874846.

Keywords: 24-h; Clinical study; Intraocular pressure; Netarsudil; Nocturnal; Ocular hypertension; Open-angle glaucoma.

Figures

Fig. 1
Fig. 1
Flow diagram of study design. IOP Intraocular pressure
Fig. 2
Fig. 2
Change from pre-treatment to post-treatment in study eye mean nocturnal intraocular pressure (a) and mean diurnal intraocular pressure (b). CI Confidence interval
Fig. 3
Fig. 3
Study eye mean intraocular pressure at each 24-h time point assessed pre-treatment and post-treatment for netarsudil (a) and vehicle (b)

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