Safety and tolerability of topical polyhexamethylene biguanide: a randomised clinical trial in healthy adult volunteers.

Autor:	Papa V; SIFI S.p.A., 36, via Ercole Patti, 95025 Lavinaio (Catania), Italy, Lavinaio, Italy., van der Meulen I; Amsterdam UMC Locatie AMC, Amsterdam, Netherlands., Rottey S; DRUG Research Unit, Ghent, Belgium., Sallet G; Ooginstituut, Aalst, Belgium., Overweel J; PSR Group BV, Hoofddorp, Netherlands., Asero N; SIFI SpA, Catania, Italy., Minassian DC; Epivision Ophthalmic Epidemiology Consultants, Penn, UK., Dart JKG; Corneal & External Disease, Moorfields Eye Hospital NHS Foundation Trust, London, UK j.dart@ucl.ac.uk.; Ocular Biology & Therapeutics, UCL Institute of Ophthalmology, London, UK.
Jazyk:	angličtina
Zdroj:	The British journal of ophthalmology [Br J Ophthalmol] 2022 Feb; Vol. 106 (2), pp. 190-196. Date of Electronic Publication: 2020 Nov 25.
DOI:	10.1136/bjophthalmol-2020-317848
Abstrakt:	Background and Aims: Polyhexamethyl biguanide (PHMB), a widely used topical treatment for Acanthamoeba keratitis (AK), is unlicensed with no formal safety assessment. This study evaluated its safety and tolerability. Methods: A prospective, randomised, double-masked controlled trial in 90 healthy volunteers. Subjects were treated with topical 0.04%, 0.06%, 0.08% PHMB or placebo (vehicle) 12× daily for 7 days, then 6× daily for 7 days. The rates of dose-limiting adverse events (DLAEs) leading to interruption of dosing, mild adverse events (AEs) (not dose limiting) and incidental AEs (unrelated to treatment) were compared. The primary outcome was the difference between treatments for DLAE rates. Results: 5/90 subjects developed DLAE within <1-4 days of starting treatment; 2/5 using PHMB 0.06% and 3/5 PHMB 0.08%. These resolved within 1-15 days. There were no significant differences in DLAE between treatment groups. Mild AEs occurred in 48/90 subjects (including placebo). There was no trend for an increased incidence of any AE with increasing concentrations of PHMB, except for corneal punctate keratopathy with PHMB 0.08%, which fully resolved within 7-14 days. Conclusion: These findings are reassuring for PHMB 0.02% users. They also suggest that higher PHMB concentrations may show acceptable levels of tolerance and toxicity in AK subjects, whose susceptibility to AE may be greater than for the normal eyes in this study. Given the potential benefits of higher PHMB concentrations for treating deep stromal invasion in AK, we think that the use of PHMB 0.08% is justified in treatment trials. Trial Registration Number: NCT02506257. Competing Interests: Competing interests: Vincenzo Papa and Antonino Asero are employees of SIFI S.p.A. who manufacture and supply PHMB eye drops in Italy, and who are carrying out studies to develop it as a licenced therapy for the treatment of Acanthamoeba keratitis in Europe. John Dart and Darwin Minassian are consultants to SIFI SpA. The remaining authors have no proprietary or commercial interest in any materials discussed in this article. (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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