Back to Search
Start Over
Additive Intraocular Pressure-Lowering Effects of the Rho Kinase Inhibitor Ripasudil (K-115) Combined With Timolol or Latanoprost: A Report of 2 Randomized Clinical Trials.
- Source :
-
JAMA ophthalmology [JAMA Ophthalmol] 2015 Jul; Vol. 133 (7), pp. 755-61. - Publication Year :
- 2015
-
Abstract
- Importance: Ripasudil hydrochloride hydrate (K-115), a novel rho kinase inhibitor, provides statistically significant intraocular pressure (IOP)-lowering effects and has a tolerable safety profile. However, no studies have evaluated ripasudil combined with β-blockers and prostaglandin analogues.<br />Objective: To evaluate the additive IOP-lowering effects and the safety of ripasudil, 0.4%, combined with timolol, 0.5%, or latanoprost, 0.005%, in patients with primary open-angle glaucoma or ocular hypertension.<br />Design, Setting, and Participants: We conducted 2, multicenter, randomized, double-masked, parallel group comparison studies of ripasudil-timolol and ripasudil-latanoprost in 29 and 36 Japanese clinical centers, respectively. Analyses were performed on an intention-treat-treat basis. After appropriate run-in periods with timolol or latanoprost, 208 and 205 patients whose IOP levels were 18 mm Hg or higher were enrolled in the ripasudil-timolol and ripasudil-latanoprost groups, respectively. Enrollment began December 1, 2011, and follow-up was completed on September 7, 2012, in the ripasudil-timolol study. Enrollment began December 1, 2011, and follow-up was completed on September 27, 2012, in the ripasudil-latanoprost study.<br />Interventions: Patients were subdivided into 2 groups in each study and were treated with ripasudil or placebo twice daily for 8 weeks.<br />Main Outcomes and Measures: The IOP reductions in the ripasudil and placebo groups were analyzed with a repeated-measures analysis of variance model at weeks 4, 6, and 8, at trough (before instillation [9 am]) and peak (2 hours after instillation [11 am]) levels.<br />Results: In the ripasudil-timolol study, the mean IOP reductions from baseline in the ripasudil and placebo groups were -2.4 and -1.5 mm Hg at 9 am for a difference of 0.9 mm Hg (95% CI, 0.4-1.3 mm Hg; P < .001) and -2.9 and -1.3 mm Hg at 11 am for a difference of 1.6 mm Hg (95% CI, 1.1-2.1 mm Hg; P < .001), respectively. In the ripasudil-latanoprost study, those IOP reductions were -2.2 and -1.8 mm Hg at 9 am for a difference of 0.4 mm Hg (95% CI, -0.0 to 0.9 mm Hg; P = .06) and -3.2 and -1.8 mm Hg at 11 am for a difference of 1.4 mm Hg (95% CI, 0.9-1.9 mm Hg; P < .001), respectively. The most frequently reported adverse event was conjunctival hyperemia, which was mild and in most cases resolved without treatment before the next instillation.<br />Conclusions and Relevance: These clinical trials found additive IOP-lowering effects of ripasudil from placebo at trough and peak levels in combination with timolol and at peak level in combination with latanoprost. However, a definitive difference in the addition of placebo to latanoprost was not identified in the trough level.<br />Trial Registration: clinicaltrials.jp Identifiers: JAPIC111700 and JAPIC111701.
- Subjects :
- Aged
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Drug Therapy, Combination
Female
Follow-Up Studies
Glaucoma, Open-Angle diagnosis
Humans
Isoquinolines adverse effects
Japan
Latanoprost
Male
Middle Aged
Ocular Hypertension diagnosis
Ophthalmic Solutions administration & dosage
Ophthalmic Solutions adverse effects
Prostaglandins F, Synthetic administration & dosage
Prostaglandins F, Synthetic adverse effects
Severity of Illness Index
Sulfonamides adverse effects
Time Factors
Timolol adverse effects
Tonometry, Ocular
Treatment Outcome
rho-Associated Kinases administration & dosage
rho-Associated Kinases antagonists & inhibitors
Glaucoma, Open-Angle drug therapy
Isoquinolines administration & dosage
Ocular Hypertension drug therapy
Sulfonamides administration & dosage
Timolol administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 2168-6173
- Volume :
- 133
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- JAMA ophthalmology
- Publication Type :
- Academic Journal
- Accession number :
- 25880207
- Full Text :
- https://doi.org/10.1001/jamaophthalmol.2015.0525