Efficacy of Topically Administered Rho-Kinase Inhibitor AR-12286 in Patients With Exfoliation Syndrome and Ocular Hypertension or Glaucoma

To evaluate the efficacy of rho-associated protein kinase inhibitor, AR-12286 topical solution, for its effect in eyes with exfoliation syndrome (XFS) and ocular hypertension (OHT) or exfoliative glaucoma (XFG) and examine any lasting effect on intraocular pressure (IOP) after discontinuation. Prosp...

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Vydáno v:Journal of glaucoma Ročník 25; číslo 9; s. e807
Hlavní autoři: Skaat, Alon, Jasien, Jessica V, Ritch, Robert
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.09.2016
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ISSN:1536-481X, 1536-481X
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Abstract To evaluate the efficacy of rho-associated protein kinase inhibitor, AR-12286 topical solution, for its effect in eyes with exfoliation syndrome (XFS) and ocular hypertension (OHT) or exfoliative glaucoma (XFG) and examine any lasting effect on intraocular pressure (IOP) after discontinuation. Prospective, double-masked, randomized, interventional study. Patients with XFS and OHT or XFG were enrolled. The study eyes were treated once daily with AR-12286, randomized to 0.5% or 0.7% for 24 weeks. Visits included baseline, 1, 4, and 12 weeks after drug initiation; at 12 weeks AR-12286 was discontinued for 1 week and was resumed at week 13. At the week 24 visit, AR-12286 was discontinued, and a final reexamination was performed at week 25. Ten patients were treated. Mean baseline IOP was 25±2.4 mm Hg, mean IOP was reduced to 19.1±2.3 mm Hg at 1 week (P<0.001), 17.5±3.6 mm Hg at 4 weeks (P<0.001), and 17.4±3.6 mm Hg at 12 weeks (P<0.001), yielding an average IOP reduction of 23.6%, 30%, and 30.4%, respectively. At the week 13 visit, 1 week after the drug was discontinued, mean IOP increased to 21.6±5.4 mm Hg (P=0.06 compared with baseline visit). At week 24, the mean IOP was 21.8±7.8 mm Hg (P=0.2, and AR-12286 was discontinued). At week 25, the mean IOP was 21.3±5.3 mm Hg (P=0.06). AR-12286 was well tolerated and provided statistically significant reduction in IOP in patients with XFS and OHT or XFG. This drug may represent an additional therapeutic paradigm for the treatment of XFG.
AbstractList To evaluate the efficacy of rho-associated protein kinase inhibitor, AR-12286 topical solution, for its effect in eyes with exfoliation syndrome (XFS) and ocular hypertension (OHT) or exfoliative glaucoma (XFG) and examine any lasting effect on intraocular pressure (IOP) after discontinuation. Prospective, double-masked, randomized, interventional study. Patients with XFS and OHT or XFG were enrolled. The study eyes were treated once daily with AR-12286, randomized to 0.5% or 0.7% for 24 weeks. Visits included baseline, 1, 4, and 12 weeks after drug initiation; at 12 weeks AR-12286 was discontinued for 1 week and was resumed at week 13. At the week 24 visit, AR-12286 was discontinued, and a final reexamination was performed at week 25. Ten patients were treated. Mean baseline IOP was 25±2.4 mm Hg, mean IOP was reduced to 19.1±2.3 mm Hg at 1 week (P<0.001), 17.5±3.6 mm Hg at 4 weeks (P<0.001), and 17.4±3.6 mm Hg at 12 weeks (P<0.001), yielding an average IOP reduction of 23.6%, 30%, and 30.4%, respectively. At the week 13 visit, 1 week after the drug was discontinued, mean IOP increased to 21.6±5.4 mm Hg (P=0.06 compared with baseline visit). At week 24, the mean IOP was 21.8±7.8 mm Hg (P=0.2, and AR-12286 was discontinued). At week 25, the mean IOP was 21.3±5.3 mm Hg (P=0.06). AR-12286 was well tolerated and provided statistically significant reduction in IOP in patients with XFS and OHT or XFG. This drug may represent an additional therapeutic paradigm for the treatment of XFG.
To evaluate the efficacy of rho-associated protein kinase inhibitor, AR-12286 topical solution, for its effect in eyes with exfoliation syndrome (XFS) and ocular hypertension (OHT) or exfoliative glaucoma (XFG) and examine any lasting effect on intraocular pressure (IOP) after discontinuation.PURPOSETo evaluate the efficacy of rho-associated protein kinase inhibitor, AR-12286 topical solution, for its effect in eyes with exfoliation syndrome (XFS) and ocular hypertension (OHT) or exfoliative glaucoma (XFG) and examine any lasting effect on intraocular pressure (IOP) after discontinuation.Prospective, double-masked, randomized, interventional study. Patients with XFS and OHT or XFG were enrolled. The study eyes were treated once daily with AR-12286, randomized to 0.5% or 0.7% for 24 weeks. Visits included baseline, 1, 4, and 12 weeks after drug initiation; at 12 weeks AR-12286 was discontinued for 1 week and was resumed at week 13. At the week 24 visit, AR-12286 was discontinued, and a final reexamination was performed at week 25.METHODSProspective, double-masked, randomized, interventional study. Patients with XFS and OHT or XFG were enrolled. The study eyes were treated once daily with AR-12286, randomized to 0.5% or 0.7% for 24 weeks. Visits included baseline, 1, 4, and 12 weeks after drug initiation; at 12 weeks AR-12286 was discontinued for 1 week and was resumed at week 13. At the week 24 visit, AR-12286 was discontinued, and a final reexamination was performed at week 25.Ten patients were treated. Mean baseline IOP was 25±2.4 mm Hg, mean IOP was reduced to 19.1±2.3 mm Hg at 1 week (P<0.001), 17.5±3.6 mm Hg at 4 weeks (P<0.001), and 17.4±3.6 mm Hg at 12 weeks (P<0.001), yielding an average IOP reduction of 23.6%, 30%, and 30.4%, respectively. At the week 13 visit, 1 week after the drug was discontinued, mean IOP increased to 21.6±5.4 mm Hg (P=0.06 compared with baseline visit). At week 24, the mean IOP was 21.8±7.8 mm Hg (P=0.2, and AR-12286 was discontinued). At week 25, the mean IOP was 21.3±5.3 mm Hg (P=0.06).RESULTSTen patients were treated. Mean baseline IOP was 25±2.4 mm Hg, mean IOP was reduced to 19.1±2.3 mm Hg at 1 week (P<0.001), 17.5±3.6 mm Hg at 4 weeks (P<0.001), and 17.4±3.6 mm Hg at 12 weeks (P<0.001), yielding an average IOP reduction of 23.6%, 30%, and 30.4%, respectively. At the week 13 visit, 1 week after the drug was discontinued, mean IOP increased to 21.6±5.4 mm Hg (P=0.06 compared with baseline visit). At week 24, the mean IOP was 21.8±7.8 mm Hg (P=0.2, and AR-12286 was discontinued). At week 25, the mean IOP was 21.3±5.3 mm Hg (P=0.06).AR-12286 was well tolerated and provided statistically significant reduction in IOP in patients with XFS and OHT or XFG. This drug may represent an additional therapeutic paradigm for the treatment of XFG.CONCLUSIONSAR-12286 was well tolerated and provided statistically significant reduction in IOP in patients with XFS and OHT or XFG. This drug may represent an additional therapeutic paradigm for the treatment of XFG.
Author Ritch, Robert
Skaat, Alon
Jasien, Jessica V
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SubjectTerms Administration, Topical
Aged
Aged, 80 and over
Antihypertensive Agents - administration & dosage
Dose-Response Relationship, Drug
Double-Blind Method
Exfoliation Syndrome - drug therapy
Exfoliation Syndrome - physiopathology
Female
Follow-Up Studies
Glaucoma - drug therapy
Glaucoma - physiopathology
Humans
Intraocular Pressure - drug effects
Isoquinolines - administration & dosage
Male
Middle Aged
Ocular Hypertension - drug therapy
Ocular Hypertension - physiopathology
Ophthalmic Solutions - administration & dosage
Prospective Studies
rho-Associated Kinases - antagonists & inhibitors
Treatment Outcome
Title Efficacy of Topically Administered Rho-Kinase Inhibitor AR-12286 in Patients With Exfoliation Syndrome and Ocular Hypertension or Glaucoma
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