TY - JOUR
T1 - Safety and tolerability of topical polyhexamethylene biguanide: A randomised clinical trial in healthy adult volunteers
AU - Papa, Vincenzo
AU - van der Meulen, Ivanka
AU - Rottey, Sylvie
AU - Sallet, Guy
AU - Overweel, Jolanda
AU - Asero, Nino
AU - Minassian, Darwin C.
AU - Dart, John K. G.
N1 - Funding Information: Funding The study was funded by the European Union under the Seventh Framework Program (Grant no. 304661) and by SIFI SpA (Catania, Italy), no grant number. Part of John Dart’s salary was paid by the Moorfields Eye Hospital and UCL Institute of Ophthalmology National Institute of Research (NIHR) Biomedical Research Centre (BRC), no grant number. Publisher Copyright: © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
KW - Clinical Trial
KW - Cornea
KW - Drugs
KW - Infection
KW - Treatment Medical
UR - http://www.scopus.com/inward/record.url?scp=85096900468&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/bjophthalmol-2020-317848
DO - https://doi.org/10.1136/bjophthalmol-2020-317848
M3 - Article
C2 - 33239413
SN - 0007-1161
VL - 106
SP - 190
EP - 196
JO - British journal of ophthalmology
JF - British journal of ophthalmology
IS - 2
M1 - 317848
ER -