Long-term intraocular pressure-lowering efficacy and safety of ripasudil-brimonidine fixed-dose combination for glaucoma and ocular hypertension: a multicentre, open-label, phase 3 study

Hidenobu Tanihara; Tetsuya Yamamoto; Makoto Aihara; Noriko Koizumi; Atsuki Fukushima; Koji Kawakita; Satoshi Kojima; Toka Nakamura; Hideki Suganami; K-232 Clinical Study Group

doi:10.1007/s00417-024-06388-y

Long-term intraocular pressure-lowering efficacy and safety of ripasudil-brimonidine fixed-dose combination for glaucoma and ocular hypertension: a multicentre, open-label, phase 3 study

Graefes Arch Clin Exp Ophthalmol. 2024 Mar 2. doi: 10.1007/s00417-024-06388-y. Online ahead of print.

Authors

Hidenobu Tanihara¹, Tetsuya Yamamoto², Makoto Aihara³, Noriko Koizumi⁴, Atsuki Fukushima⁵, Koji Kawakita⁶, Satoshi Kojima⁶, Toka Nakamura⁷, Hideki Suganami⁸; K-232 Clinical Study Group

Collaborators

Affiliations

¹ Department of Ophthalmology, Biei Municipal Hospital, 3-8-35 Naka-machi, Biei Town, Kamikawa-gun, Hokkaido, 071-0207, Japan. tanihara@pearl.ocn.ne.jp.
² Prof. Kazuo Iwata Memorial Kaijin Glaucoma Center, Kaiya Eye Clinic, Shizuoka, Japan.
³ Department of Ophthalmology, The University of Tokyo, Tokyo, Japan.
⁴ Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyoto, Japan.
⁵ Department of Ophthalmology, Tsukazaki Hospital, Hyogo, Japan.
⁶ Pharmaceutical Clinical Development Management Department, Kowa Company, Ltd., Tokyo, Japan.
⁷ Medical Affairs Department, Kowa Company, Ltd., Tokyo, Japan.
⁸ Data Science Center, Kowa Company, Ltd., Tokyo, Japan.

PMID: 38430227
DOI: 10.1007/s00417-024-06388-y

Abstract

Purpose: To evaluate the long-term efficacy and safety of ripasudil-brimonidine fixed-dose combination (RBFC), a new intraocular pressure (IOP)-lowering medication for glaucoma and ocular hypertension (OHT).

Methods: This prospective, multicentre (23 sites in Japan), open-label study enrolled patients with primary open-angle glaucoma (POAG), OHT or exfoliative glaucoma and assigned them to one of four combination therapy cohorts, based on previous treatment(s) received: prostaglandin (PG) analogue (Cohort 1); PG analogue and beta-adrenoceptor blocker (β-blocker) (Cohort 2); PG analogue, β-blocker and carbonic anhydrase inhibitor (Cohort 3); or other/no treatment (Cohort 4). After a ≥ 4-week screening period, eligible patients received twice-daily RBFC for 52 weeks in addition to the treatments they were already receiving. Efficacy was assessed by change in IOP from baseline through week 52. Adverse events and adverse drug reactions (ADRs) were monitored throughout.

Results: In total, 179 patients from Cohort 1 (n = 48), Cohort 2 (n = 44), Cohort 3 (n = 41) and Cohort 4 (n = 46) entered the RBFC treatment period. For all cohorts, mean IOP was significantly reduced at 11:00 (2 h after instillation of RBFC) through week 52 with the changes from baseline at week 52 of - 2.7 to - 4.1 mmHg across cohorts; all p < 0.001. Common ADRs were conjunctival hyperaemia (58%), allergic conjunctivitis (18%) and blepharitis (17%), most of which were mild in severity.

Conclusion: These data demonstrated the long-term efficacy and safety of RBFC, both alone and in combination with other anti-glaucoma agents. RBFC may offer a new treatment option for the long-term management of glaucoma and OHT.

Trial registration: Japan Registry of Clinical Trials Identifier: jRCT2080225063.

Date of registration: 17 February 2020.

Keywords: Glaucoma; Intraocular pressure; Long-term treatment; Ocular hypertension; Ripasudil-brimonidine fixed-dose combination.