Open AccessPhase 2b, Randomized, 3-Month, Dose-Finding Study of Sepetaprost in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: The ANGEL Study
Author(s) -
David Wirta,
Yasuaki Kuwayama,
Fenghe Lu,
Hui Shao,
Noriko Odani-Kawabata
Publication year - 2022
Publication title -
journal of ocular pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 61
eISSN - 1557-7732
pISSN - 1080-7683
DOI - 10.1089/jop.2021.0077
Subject(s) - latanoprost , medicine , ocular hypertension , placebo , intraocular pressure , glaucoma , open angle glaucoma , adverse effect , clinical endpoint , ophthalmology , randomized controlled trial , anesthesia , surgery , alternative medicine , pathology
Purpose: This phase 2b, randomized, observer-masked, placebo- and active-controlled, parallel-group, multinational (USA and Japan), multicenter study (NCT03216902) assessed the optimal dose of sepetaprost ophthalmic solution in patients with primary open-angle glaucoma or ocular hypertension. Methods: After washout, patients ≥18 years (USA) or ≥20 years of age (Japan) received once-daily sepetaprost for 3 months [0.0005% ( n = 43); 0.001% ( n = 43); 0.002% ( n = 44); and 0.003% ( n = 45)], latanoprost 0.005% ( n = 44) or placebo until week 6, followed by sepetaprost 0.003% until month 3 ( n = 22). Safety assessments included adverse event (AE) occurrence. Results: Baseline mean diurnal intraocular pressure (IOP) was 24.3 mmHg for latanoprost and ranged between 24.1 and 24.5 mmHg for the sepetaprost groups. Sepetaprost 0.002% had the lowest IOP at each month 3 time point (9:00 AM; 1:00 PM; 5:00 PM) of all sepetaprost concentrations (mean ± standard error: 17.6 ± 0.5; 17.4 ± 0.4; 16.7 ± 0.4 mmHg); similar values were observed with latanoprost (18.1 ± 0.6; 17.3 ± 0.5; 17.2 ± 0.5 mmHg). A positive dose-response relationship was observed with the 3 lower sepetaprost doses; sepetaprost 0.002% had numerically greater IOP-lowering effects than sepetaprost 0.003%. All sepetaprost doses had statistically significantly greater IOP reductions from baseline versus placebo at week 6 ( P < 0.0001). This IOP-lowering effect was consistent between Japan- and USA-based patients. Most AEs were mild and occurred numerically less frequently with sepetaprost 0.002% (34.1%) versus latanoprost (50.0%). The most frequently reported AE was conjunctival hyperemia. Conclusion: In this study, sepetaprost 0.002% was the optimal concentration, showing comparable IOP-lowering efficacy and safety with latanoprost 0.005%. Most AEs were mild; occurrence was numerically lower with sepetaprost 0.002% than latanoprost 0.005%.