Phase 1 Clinical Trials of a Selective Rho Kinase Inhibitor, K-115

Abstract

Glaucoma has been regarded as the leading cause of blindness in the world.¹ Because several large-scale clinical studies^2-4 have demonstrated a correlation between intraocular pressure (IOP) reduction and the onset and progression of glaucoma, IOP reduction has been considered a useful therapeutic intervention for the management of patients with glaucoma, even in patients with normal-tension glaucoma. For the treatment of glaucoma, several drugs to reduce IOP have been developed and used in clinical practice, such as prostaglandin analogues and adrenergic β-receptor antagonists. Prostaglandin analogues and some other agents lower IOP by improving uveoscleral outflow of aqueous humor.⁵ In contrast, β-blockers and carbonic anhydrase inhibitors cause IOP reduction by inhibition of aqueous humor production.^6,7 In addition, miotic agents (including pilocarpine) have been shown to lower IOP by contraction of ciliary muscle and subsequent improvement in outflow.⁸ To date, no IOP-lowering drugs directly modulating conventional outflow have been available clinically to treat glaucoma.