Dataset Information

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

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?ConclusionNetarsudil exhibited consistent IOP-lowering efficacy over a 24-h period in this short-term study.

Trial registration

Clinicaltrials.gov identifier: NCT02874846.

SUBMITTER: Peace JH

PROVIDER: S-EPMC7887148 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Peace James H JH McKee Hayley J HJ Kopczynski Casey C CC

Ophthalmology and therapy 20201126 1

<h4>Introduction</h4>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.<h4>Me ...[more]

PMID: 33244711

Similar Datasets

Project description:IntroductionNetarsudil reduces intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM) pathway and decreasing episcleral venous pressure. The primary objective of this phase 2 study was to evaluate ocular hypotensive efficacy and safety of three netarsudil concentrations (0.01%, 0.02%, and 0.04%) relative to its placebo over 4 weeks in Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).MethodsPatients were randomized to one of four treatment arms, netarsudil ophthalmic solution 0.01%, 0.02%, 0.04%, or placebo, and treated once-daily (QD) in the evening (P.M.) for 4 weeks. The primary efficacy variable was mean diurnal IOP (average of diurnal time points at 9 A.M., 11 A.M., and 4 P.M.) at week 4.ResultsA total of 215 patients were randomized and 207 (96.3%) completed the study. The mean of mean diurnal IOP at baseline ranged from 20.28 to 21.14 mmHg across groups. At week 4, least squares (LS) mean of mean diurnal IOP adjusted for baseline was 16.53, 15.82, 16.06, and 18.94 mmHg in the netarsudil 0.01%, 0.02%, 0.04%, and placebo groups, respectively, demonstrating the superiority of netarsudil (all concentrations) over placebo. At week 4, mean reduction (mean percentage reduction) from baseline in mean diurnal IOP was 4.10 (19.8%), 4.80 (23.5%), 4.81 (23.8%), and 1.73 mmHg (8.2%), respectively, demonstrating statistically significant reductions (p < 0.0001) in all netarsudil concentrations over placebo. Adverse events (AEs) occurred in a concentration-dependent manner, and the incidence of ocular AEs was 34.5%, 42.6%, 68.6%, and 9.1% in the netarsudil 0.01%, 0.02%, 0.04%, and placebo groups, respectively. The most frequently reported AE was conjunctival hyperemia, with an incidence of 23.6%, 37.0%, 56.9%, and 1.8%, respectively. No serious AEs were reported.ConclusionNetarsudil ophthalmic solutions 0.01%, 0.02%, and 0.04% dosed QD (P.M.) demonstrated superiority to placebo in terms of hypotensive effectiveness at week 4 and were found to be safe and generally well tolerated. Netarsudil 0.02% QD provided an optimal efficacy and safety profile for the treatment of Japanese patients with POAG or OHT.Trial registrationNCT03844945.

Project description:INTRODUCTION:New open-angle glaucoma (OAG) and ocular hypertension (OHT) therapies that reduce treatment burden and improve outcomes relative to currently available agents are needed. Netarsudil, a novel Rho kinase inhibitor approved by the US Food and Drug Administration, reduces intraocular pressure (IOP) by increasing trabecular outflow. Two phase 3 superiority studies compared a fixed-dose combination (FDC) of netarsudil and the prostaglandin latanoprost with each active component for IOP-lowering efficacy. METHODS:Pooled efficacy and safety data were analyzed from MERCURY-1 and -2 studies in patients with OAG or OHT. Patients instilled one drop of netarsudil (0.02%)/latanoprost (0.005%) FDC (n?=?483), netarsudil (0.02%, n?=?499), or latanoprost (0.005%, n?=?486) into each eye once-daily between 20:00 and 22:00. IOP was measured at 08:00, 10:00, and 16:00 at weeks 2, 6, and the primary endpoint at month 3. RESULTS:Baseline mean diurnal IOP was 23.6, 23.6, and 23.5 mmHg in netarsudil/latanoprost FDC, netarsudil, and latanoprost groups, respectively. Mean diurnal IOP in each group was 15.3, 18.1, and 17.5 mmHg at week 2, 15.7, 18.4, and 17.4 mmHg at week 6, and 15.8, 18.4, and 17.3 mmHg at week 12. The netarsudil/latanoprost FDC met criteria for superiority compared with each active component (p?<?0.0001 for all nine time points). At month 3, among patients randomized to netarsudil/latanoprost FDC or latanoprost, 58.4% vs 37.3% (p?<?0.0001) achieved IOP???16 mmHg. Among patients randomized to netarsudil/latanoprost FDC or netarsudil or latanoprost, 30.9% vs 5.9% (p?<?0.0001) vs 8.5% (p?<?0.0001) achieved at least a 40% reduction from baseline in mean diurnal IOP. Pooled safety results were consistent with individual MERCURY studies. CONCLUSION:Once-daily netarsudil/latanoprost FDC produced statistically significant and clinically relevant reductions in mean IOP that were statistically superior to IOP reductions achieved by netarsudil and latanoprost monotherapy. Results of the pooled efficacy and safety analyses were consistent with the individual studies. TRIAL REGISTRATION:ClinicalTrials.gov identifiers, NCT02558400 and NCT02674854.

Project description:IntroductionFixed-combination glaucoma medications are commonly used to achieve target intraocular pressure (IOP) reduction in patients uncontrolled with monotherapy; however, ocular discomfort associated with eye drops can decrease adherence. This study assessed the efficacy and tolerability of twice-daily fixed-combination brinzolamide 1%/timolol 0.5% (BRINZ/TIM-FC) in Latin American patients transitioned from fixed-combination brimonidine 0.2%/timolol 0.5% (BRIM/TIM-FC) because of insufficient IOP control or treatment intolerance.MethodsThis 8-week, open-label, prospective study was conducted at six sites in Argentina, Chile, and Mexico. Enrolled patients were aged ≥18 years with open-angle glaucoma (including primary, exfoliative, or pigment-dispersion glaucoma) or ocular hypertension with IOP of 19-35 mmHg in ≥1 eye at baseline (on BRIM/TIM-FC). Patients self-administered BRINZ/TIM-FC to both eyes at 8 a.m. and 8 p.m. daily for 8 weeks. The primary and secondary efficacy endpoints were mean IOP change from baseline at week 8 and percentage of patients achieving target IOP (≤18 mmHg) at week 8, respectively. Exploratory endpoints included patient and investigator preference for treatment at week 8. Adverse events (AEs) were assessed as the safety endpoint.ResultsFifty patients (mean ± SD age, 66.7 ± 11.5 years) received BRINZ/TIM-FC, and 49 were included in the intent-to-treat population. Mean ± SD IOP was significantly reduced from baseline after 8 weeks of treatment with BRINZ/TIM-FC (-3.6 ± 3.0 mmHg; P < 0.0001, Wilcoxon signed-rank test; 17.1% reduction). Overall, 55.3% of patients achieved IOP ≤18 mmHg at week 8. Significantly more patients (89.4%) and investigators (95.7%) preferred BRINZ/TIM-FC to BRIM/TIM-FC (both P < 0.0001, exact binomial test). Of the 13 AEs observed, 8 were related to BRINZ/TIM-FC; the most common treatment-related AEs were eye irritation (n = 4) and abnormal sensation in the eye (n = 2).ConclusionBRINZ/TIM-FC provides an effective and well-tolerated treatment option for patients transitioned from BRIM/TIM-FC.

Project description:Medications to control intraocular pressure (IOP) are frequently preserved using benzalkonium chloride (BAK), which can negatively affect the ocular surface. Data are needed to assess efficacy and safety of prostaglandin drugs preserved with and without BAK. The present study compared the efficacy and safety of BAK-free travoprost 0.004% (TRAV) and BAK 0.02%-preserved bimatoprost 0.01% (BIM) during late-day time points in patients with open-angle glaucoma or ocular hypertension.This was a 12-week, phase 4, randomized, investigator-masked, crossover study. 84 patients with IOP ?24 and <36 mmHg were randomized 1:1 to receive once-daily TRAV or BIM for 6 weeks followed by an additional 6-week crossover period. IOP was measured at the end of each treatment period at 4, 6, and 8 pm. TRAV was considered noninferior to BIM if the upper limit of the 95% CI of the between-group difference in mean IOP was ?1.5 mmHg. Adverse events were assessed throughout the study.One patient discontinued due to allergic conjunctivitis, and 2 patients with missing data were excluded; 81 patients were included in the per-protocol population (mean ± SD age, 58.3 ± 11.4 years; TRAV/BIM, n = 41; BIM/TRAV, n = 40). After 6 weeks, mean IOP with TRAV (17.4 ± 2.7 mmHg; change from baseline, -6.0 mmHg) was similar to BIM (17.2 ± 2.6 mmHg; change from baseline, -6.3 mmHg); the between-group difference was 0.22 mmHg (95% CI, -0.22 to 0.67). Thus, noninferiority of TRAV versus BIM was demonstrated. Mean IOP at each time point and mean and percentage IOP change from baseline were not significantly different between treatments. All treatment-emergent adverse events were mild to moderate. The incidences of mild ocular hyperemia with TRAV and BIM were 31% and 39%, respectively; moderate hyperemia was observed in 2% of patients receiving BIM.Late-day IOP-lowering efficacy of BAK-free TRAV was noninferior to that of BAK 0.02%-preserved BIM; both reduced baseline IOP by 25%. Both treatments were well tolerated, although a higher incidence of moderate ocular hyperemia was observed with BIM.ClinicalTrials.gov identifier, NCT01464424; registered November 1, 2011.

Dataset Information

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

Introduction

Methods

Results

Trial registration

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure