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Vincenzo Papa, Ivanka J.E. van Der Meulen, Sylvie Rottey, Guy Sallet, Iolanda Overweel, Margreet op 't Hof, Antonino Asero, John Kenneth George Dart; Ocular safety of high doses Polyhexanide (PHMB) in healthy volunteers. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5170.
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© ARVO (1962-2015); The Authors (2016-present)
PHMB 0.02% eye drops are widely used in the treatment of Acanthamoeba keratitis. However, higher concentrations of PHMB may be required for patients with Acanthamoeba invading the deep stroma. To evaluate the safety and tolerability of three dose levels (0.04%, 0.06% and 0.08%) of preservative-free PHMB ophthalmic solution, a double-masked, placebo-controlled, parallel-group multicenter Phase I study was performed in healthy volunteers
Ninety volunteers (44 M/46 F, age 18-55 years) were randomised to 1 of the 4 study arms: 0.04%, 0.06%, 0.08% PHMB and placebo, in a 3:3:3:1 ratio respectively. Subjects were dosed 12 times daily (1 drop every hour, daytime only) for 7 consecutive days followed by 6 times daily (1 drop every 2 hours) for 7 days.The primary outcome measure was the rate of dose limiting events (DLEs) leading to interruption of dosing. The frequency of treatment emergent adverse events (TEAEs) as well as serious AEs (SAEs) starting after the first administration of the study drug were also computed. The rate of occurrence of SAEs, DLEs and TEAEs were compared between groups by Fisher’s exact test. Statistical tests were performed 2-sided and with a 5% significance level. A 95% confidence interval for the difference between each respective dose and placebo and p-value was calculated.
During the study no SAEs occurred. The global DLE rate was 5.6%. DLEs occurred in five subjects (2 dosed with 0.06% PHMB and 3 with 0.08% PHMB). No statistically significant differences between treatment groups were observed. Events causing DLEs (burning, itching, conjunctival hyperaemia, corneal staining) ranged from mild to moderate intensity. The global TEAE rate was 58.9%. TEAEs occurred in 53 subjects with a frequency of 55.6%, 38.5%, 78.6% and 59.3% in the placebo, 0.04%, 0.06% and 0.08% PHMB dose groups respectively. Only the difference between the 0.04% and 0.06% PHMB groups was statistically significant (p=0.0051). Most frequently reported events were conjunctival staining, corneal staining, pain after instillation and conjunctival hyperemia. Most TEAEs were of mild intensity.
Only mild to moderate ocular AEs occurred after intensive dosing with high concentrations of PHMB. Therefore, it is considered safe to investigate 0.08% PHMB eye drops in a Phase III study in patients with Acanthamoeba keratitis.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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