One-year clinical evaluation of 0.4% ripasudil (K-115) in patients with open-angle glaucoma and ocular hypertension

Acta Ophthalmol. 2016 Feb;94(1):e26-34. doi: 10.1111/aos.12829. Epub 2015 Sep 4.

Abstract

Purpose: To investigate the intra-ocular pressure (IOP)-lowering effects and safety of 0.4% ripasudil (K-115), a Rho kinase inhibitor, twice daily for 52 weeks, in patients with open-angle glaucoma or ocular hypertension (OHT).

Methods: In this multicentre, prospective, open-label study, 388 patients with primary open-angle glaucoma, OHT or exfoliation glaucoma were enrolled and 354 of them were subdivided into four cohorts (monotherapy, 173; additive therapy to prostaglandin analogs, 62; β-blockers, 60; or fixed combination drugs, 59). The IOP reduction at trough and peak from baseline and adverse events was investigated.

Results: Ripasudil showed IOP-lowering effects over 52 weeks in all the analyses of monotherapy, additive therapy and both subgroups (baseline IOP ≥21 mmHg and <21 mmHg) of monotherapy. The mean IOP reductions at trough and peak at week 52 were -2.6 and -3.7 mmHg for monotherapy, and -1.4 and -2.4, -2.2 and -3.0, and -1.7 and -1.7 mmHg, respectively, for additive therapy described above. The most frequently observed adverse events were conjunctival hyperaemia (n = 264, 74.6%), blepharitis (n = 73, 20.6%) and allergic conjunctivitis (n = 61, 17.2%). Most of the conjunctival hyperaemia findings were mild (97.0%), transient and resolved spontaneously (78.0%). Although 51 patients discontinued from the study due to blepharitis and/or allergic conjunctivitis (blepharitis, 28; allergic conjunctivitis, 17; both, 6), all the events resolved with or without treatment after the discontinuation of ripasudil administration.

Conclusion: Fifty-two week administration of 0.4% ripasudil revealed IOP-lowering effects and an acceptable safety profile when administered as monotherapy or as additive therapy, in patients with open-angle glaucoma or OHT.

Keywords: K-115; glaucoma; intra-ocular pressure; rho kinase inhibitor; ripasudil.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Aged
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Glaucoma, Open-Angle / drug therapy*
  • Humans
  • Intraocular Pressure / drug effects*
  • Isoquinolines / adverse effects
  • Isoquinolines / therapeutic use*
  • Male
  • Middle Aged
  • Ocular Hypertension / drug therapy
  • Ophthalmic Solutions
  • Prospective Studies
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Tonometry, Ocular
  • rho-Associated Kinases / antagonists & inhibitors

Substances

  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Drug Combinations
  • Isoquinolines
  • K-115
  • Ophthalmic Solutions
  • Sulfonamides
  • rho-Associated Kinases