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Original Investigation | Clinical Sciences

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

Hidenobu Tanihara, MD1; Toshihiro Inoue, MD1; Tetsuya Yamamoto, MD2; Yasuaki Kuwayama, MD3; Haruki Abe, MD4; Makoto Araie, MD5 ; for the K-115 Clinical Study Group
[+] Author Affiliations
1Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
2Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan
3Fukushima Eye Clinic, Osaka, Japan
4Niigata Eye Clinic, Niigata University, Niigata, Japan
5Kanto Central Hospital, Tokyo, Japan
JAMA Ophthalmol. 2013;131(10):1288-1295. doi:10.1001/jamaophthalmol.2013.323.
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Importance  We conducted a series of phase 1 clinical trials to elucidate the efficacy and safety of the selective Rho kinase inhibitor K-115 as a candidate drug for the treatment of glaucoma. We report the intraocular pressure (IOP)–lowering effects and safety of K-115 based on our results.

Objective  To study the IOP-lowering effects and safety of topical administration of a selective Rho kinase inhibitor, K-115, in healthy male adult volunteers.

Design and Setting  Randomized, placebo-controlled, double-masked, group comparison phase 1 clinical trial.

Participants  In the initial single-instillation trial, 50 healthy volunteers were subdivided into groups and treated with placebo or K-115 in concentrations of 0.05%, 0.1%, 0.2%, 0.4%, and 0.8% in a stepwise manner. In the repeated-instillation trial, another 50 healthy volunteers were subdivided into groups and treated with placebo or K-115 in concentrations of 0.05%, 0.1%, 0.2%, 0.4%, and 0.8% twice daily for 7 days in a stepwise manner.

Main Outcomes and Measures  In these clinical trials, the administration of eyedrops and associated examinations (including IOP measurements) were performed in a double-masked manner.

Results  After single instillation of placebo or K-115 in concentrations of 0.05%, 0.1%, 0.2%, 0.4%, and 0.8%, the changes in IOP from baseline were −1.6 mm Hg for placebo and −3.4, −2.2, −2.6, −4.0, and −4.3 mm Hg, respectively, for the different concentrations 2 hours after instillation. Similar to the single-instillation trial, IOP reductions in the repeated-instillation trial were found after each instillation, with maximal reduction 1 to 2 hours after instillation. In the safety trial, slight to mild conjunctival hyperemia was found in more than half of the participants treated with K-115; it was found after each instillation and spontaneously resolved within 1½ hours.

Conclusions and Relevance  K-115 is a promising drug for lowering IOP in healthy adult eyes, with tolerable adverse events during at least short-term administration.

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Figure 1.
Levels of Intraocular Pressure (IOP) After Single Instillation of K-115

A, Levels of IOP. Values are means (SDs). B, Reduction in IOP. Values are estimates (95% CIs). *P < . 05; **P < .01 compared with the placebo group (Dunnett test).

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Figure 2.
Levels of Intraocular Pressure (IOP) During Repeated Instillation of K-115

A, Levels of IOP. Day 1 indicates IOP levels after the first instillation, and day 7 indicates IOP levels after the last instillation. Pre indicates baseline levels. The second instillation on day 1 was administered at 12 hours after the first instillation. Values are means (SDs). B, Reduction in IOP. Values are means (SDs). C, Reduction in IOP after the last instillation. Values are estimates (95% CIs).

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