Thomas R Walters1, Iqbal Ike K Ahmed2, Richard A Lewis3, Dale W Usner4, Jae Lopez5, Casey C Kopczynski5, Theresa Heah5. 1. Texan Eye PA, Austin, Texas. Electronic address: tom@nobhill.me. 2. University of Toronto, Mississauga, Ontario, Canada. 3. Aerie Pharmaceuticals, Inc., Irvine, California; Bedminster, New Jersey; and Durham, North Carolina; Sacramento Eye Consultants, Sacramento, California. 4. Statistics & Data Corporation, Tempe, Arizona. 5. Aerie Pharmaceuticals, Inc., Irvine, California; Bedminster, New Jersey; and Durham, North Carolina.
Abstract
PURPOSE: To compare the ocular hypotensive efficacy and safety of a once-daily (pm) fixed-dose combination (FDC) product containing netarsudil 0.02% and latanoprost 0.005% with monotherapy with netarsudil or latanoprost. Netarsudil is a Rho kinase inhibitor that lowers intraocular pressure (IOP) primarily by increasing trabecular (conventional) outflow. Latanoprost is the most frequently prescribed of the prostaglandin analogs, which lower IOP primarily by increasing uveoscleral outflow. DESIGN: Three-month, double-masked, randomized (1:1:1), phase 3, superiority study. PARTICIPANTS: Patients had unmedicated IOP > 20 to <36 mmHg at 8:00 am and met other standard criteria for open-angle glaucoma and ocular hypertension. METHODS: Randomization to once-daily (pm) netarsudil/latanoprost FDC, netarsudil, or latanoprost for 3 months. MAIN OUTCOME MEASURES: Mean IOP at 8:00 am, 10:00 am, and 4:00 pm at week 2, week 6, and month 3 (intent-to-treat). Statistical superiority was concluded if the P value for the comparison of netarsudil/latanoprost FDC with each component was <0.05 and the difference in mean IOP (netarsudil/latanoprost FDC minus comparator) was <0 for all time points at all visits. Safety was recorded throughout the treatment period. RESULTS:A total of 750 patients were enrolled, with 90.2%, 89.4%, and 94.4% completing 3 months of treatment with netarsudil/latanoprost FDC, netarsudil, and latanoprost, respectively. Least-squares mean treated IOP ranged from 15.3 to 16.5 mmHg for netarsudil/latanoprost FDC, 17.4 to 19.8 mmHg for netarsudil, and 17.1 to 18.1 mmHg for latanoprost. Netarsudil/latanoprost FDC met the criteria for superiority to each active component at all 9 time points (all P < 0.0001), lowering IOP by an additional 2.2 to 3.3 mmHg versus netarsudil and an additional 1.5 to 2.4 mmHg versus latanoprost. At month 3, the proportion of patients achieving mean diurnal IOP ≤ 15 mmHg was 42.1% for netarsudil/latanoprost FDC, 15.8% for netarsudil, and 18.3% for latanoprost. No treatment-related serious adverse event (AE) was observed. Treatment-related systemic AEs were minimal. The most frequent ocular AE was conjunctival hyperemia (netarsudil/latanoprost FDC, 54.5%; netarsudil, 42.7%; latanoprost, 22.3%), which was generally mild. CONCLUSIONS: Once-daily netarsudil/latanoprost FDC demonstrated IOP reductions that were statistically and clinically superior to its individual components at all 9 time points over 3 months, with tolerable ocular safety. This FDC offers a reduced treatment burden that may improve adherence and clinical outcomes.
RCT Entities:
PURPOSE: To compare the ocular hypotensive efficacy and safety of a once-daily (pm) fixed-dose combination (FDC) product containing netarsudil 0.02% and latanoprost 0.005% with monotherapy with netarsudil or latanoprost. Netarsudil is a Rho kinase inhibitor that lowers intraocular pressure (IOP) primarily by increasing trabecular (conventional) outflow. Latanoprost is the most frequently prescribed of the prostaglandin analogs, which lower IOP primarily by increasing uveoscleral outflow. DESIGN: Three-month, double-masked, randomized (1:1:1), phase 3, superiority study. PARTICIPANTS: Patients had unmedicated IOP > 20 to <36 mmHg at 8:00 am and met other standard criteria for open-angle glaucoma and ocular hypertension. METHODS: Randomization to once-daily (pm) netarsudil/latanoprost FDC, netarsudil, or latanoprost for 3 months. MAIN OUTCOME MEASURES: Mean IOP at 8:00 am, 10:00 am, and 4:00 pm at week 2, week 6, and month 3 (intent-to-treat). Statistical superiority was concluded if the P value for the comparison of netarsudil/latanoprost FDC with each component was <0.05 and the difference in mean IOP (netarsudil/latanoprost FDC minus comparator) was <0 for all time points at all visits. Safety was recorded throughout the treatment period. RESULTS: A total of 750 patients were enrolled, with 90.2%, 89.4%, and 94.4% completing 3 months of treatment with netarsudil/latanoprost FDC, netarsudil, and latanoprost, respectively. Least-squares mean treated IOP ranged from 15.3 to 16.5 mmHg for netarsudil/latanoprost FDC, 17.4 to 19.8 mmHg for netarsudil, and 17.1 to 18.1 mmHg for latanoprost. Netarsudil/latanoprost FDC met the criteria for superiority to each active component at all 9 time points (all P < 0.0001), lowering IOP by an additional 2.2 to 3.3 mmHg versus netarsudil and an additional 1.5 to 2.4 mmHg versus latanoprost. At month 3, the proportion of patients achieving mean diurnal IOP ≤ 15 mmHg was 42.1% for netarsudil/latanoprost FDC, 15.8% for netarsudil, and 18.3% for latanoprost. No treatment-related serious adverse event (AE) was observed. Treatment-related systemic AEs were minimal. The most frequent ocular AE was conjunctival hyperemia (netarsudil/latanoprost FDC, 54.5%; netarsudil, 42.7%; latanoprost, 22.3%), which was generally mild. CONCLUSIONS: Once-daily netarsudil/latanoprost FDC demonstrated IOP reductions that were statistically and clinically superior to its individual components at all 9 time points over 3 months, with tolerable ocular safety. This FDC offers a reduced treatment burden that may improve adherence and clinical outcomes.
Authors: Kelly A Leary; Juan P Steibel; Christine D Harman; Amanda L Anderson; András M Komáromy Journal: Vet Ophthalmol Date: 2021-06-04 Impact factor: 1.644
Authors: Haochen Xu; Marwa T Thomas; Dayeong Lee; Matthew T Hirabayashi; Jella A An Journal: Graefes Arch Clin Exp Ophthalmol Date: 2022-03-11 Impact factor: 3.535