PMID- 33239413
OWN - NLM
STAT- MEDLINE
DCOM- 20220422
LR  - 20220422
IS  - 1468-2079 (Electronic)
IS  - 0007-1161 (Linking)
VI  - 106
IP  - 2
DP  - 2022 Feb
TI  - Safety and tolerability of topical polyhexamethylene biguanide: a randomised 
      clinical trial in healthy adult volunteers.
PG  - 190-196
LID - 10.1136/bjophthalmol-2020-317848 [doi]
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) 
      12x daily for 7 days, then 6x 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.
CI  - (c) Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and 
      permissions. Published by BMJ.
FAU - Papa, Vincenzo
AU  - Papa V
AD  - SIFI S.p.A., 36, via Ercole Patti, 95025 Lavinaio (Catania), Italy, Lavinaio, 
      Italy.
FAU - van der Meulen, Ivanka
AU  - van der Meulen I
AD  - Amsterdam UMC Locatie AMC, Amsterdam, Netherlands.
FAU - Rottey, Sylvie
AU  - Rottey S
AD  - DRUG Research Unit, Ghent, Belgium.
FAU - Sallet, Guy
AU  - Sallet G
AD  - Ooginstituut, Aalst, Belgium.
FAU - Overweel, Jolanda
AU  - Overweel J
AD  - PSR Group BV, Hoofddorp, Netherlands.
FAU - Asero, Nino
AU  - Asero N
AD  - SIFI SpA, Catania, Italy.
FAU - Minassian, Darwin C
AU  - Minassian DC
AD  - Epivision Ophthalmic Epidemiology Consultants, Penn, UK.
FAU - Dart, John K G
AU  - Dart JKG
AUID- ORCID: 0000-0003-4090-6950
AD  - Corneal & External Disease, Moorfields Eye Hospital NHS Foundation Trust, London, 
      UK j.dart@ucl.ac.uk.
AD  - Ocular Biology & Therapeutics, UCL Institute of Ophthalmology, London, UK.
LA  - eng
SI  - ClinicalTrials.gov/NCT02506257
GR  - DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20201125
PL  - England
TA  - Br J Ophthalmol
JT  - The British journal of ophthalmology
JID - 0421041
RN  - 0 (Biguanides)
RN  - 322U039GMF (polihexanide)
SB  - IM
MH  - *Acanthamoeba Keratitis/drug therapy
MH  - Adult
MH  - *Biguanides/adverse effects
MH  - Healthy Volunteers
MH  - Humans
MH  - Prospective Studies
OTO - NOTNLM
OT  - Clinical Trial
OT  - Cornea
OT  - Drugs
OT  - Infection
OT  - Treatment Medical
COIS- 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.
EDAT- 2020/11/27 06:00
MHDA- 2022/04/23 06:00
CRDT- 2020/11/26 05:37
PHST- 2020/08/27 00:00 [received]
PHST- 2020/10/01 00:00 [revised]
PHST- 2020/10/21 00:00 [accepted]
PHST- 2020/11/27 06:00 [pubmed]
PHST- 2022/04/23 06:00 [medline]
PHST- 2020/11/26 05:37 [entrez]
AID - bjophthalmol-2020-317848 [pii]
AID - 10.1136/bjophthalmol-2020-317848 [doi]
PST - ppublish
SO  - Br J Ophthalmol. 2022 Feb;106(2):190-196. doi: 10.1136/bjophthalmol-2020-317848. 
      Epub 2020 Nov 25.