Safety and tolerability of topical polyhexamethylene biguanide: a randomised clinical trial in healthy adult volunteers.
Clinical Trial
Cornea
Drugs
Infection
Treatment Medical
Journal
The British journal of ophthalmology
ISSN: 1468-2079
Titre abrégé: Br J Ophthalmol
Pays: England
ID NLM: 0421041
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
27
08
2020
revised:
01
10
2020
accepted:
21
10
2020
pubmed:
27
11
2020
medline:
23
4
2022
entrez:
26
11
2020
Statut:
ppublish
Résumé
Polyhexamethyl biguanide (PHMB), a widely used topical treatment for 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. 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. 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. NCT02506257.
Sections du résumé
BACKGROUND AND AIMS
Polyhexamethyl biguanide (PHMB), a widely used topical treatment for
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.
Identifiants
pubmed: 33239413
pii: bjophthalmol-2020-317848
doi: 10.1136/bjophthalmol-2020-317848
doi:
Substances chimiques
Biguanides
0
polihexanide
322U039GMF
Banques de données
ClinicalTrials.gov
['NCT02506257']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
190-196Subventions
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
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.