A Novel Once-a-Day Timolol 0.1% Gel Formulation has an equivalent IOP-lowering efficacy to timolol 0.5% solution

JF Rouland1, P Morel-Mandrino2, PP Elena3, and H Polzer2

1Department of Ophthalmology, Lille, France; 2Clirophtha, Nice, France; 3MEDProject, Sauerlach, Germany

Purpose: To assess the equivalence of the IOP-lowering effect after 12 weeks of treatment with a novel once-a-day (QD) timolol 0.1% eye gel (Nyolol Gel®, Nyogel 0.1%®) formulated with an innovative mucoadhesive vehicle, containing a combination of carbomer and PVA, with a traditional timolol 0.5% solution applied twice daily (BID).

Method: A phase III, randomised, double-masked, multicentre, parallel active treatment controlled, prospective, randomized trial over 12 weeks. Five visits were scheduled: selection, baseline and Week#2, Week#4, Week#12 after treatment initiation.

Results: 210 patients were enrolled in the study. 167 patients completed the study (82 for timolol 0.1% gel, 85 for timolol 0.5% solution) and were considered for Per Protocol (PP) analysis. Statistical analysis of the primary efficacy endpoint in the PP population (change of IOP from baseline to IOP at Week#12 before the instillation in the morning as observed in the worse eye), indicated an equivalence between the two treatments: a decrease of -6.34 ± 3.29 mmHg (mean ± SD) for timolol 0.1% gel treatment, and a decrease of -6.96 ± 2.94 mmHg for timolol 0.5% solution treatment (p = 0.193). Safety and ocular tolerance were similar in the two treatment groups. Plasma levels at Week#12 before (residual levels) and 30 min. after instillation, were statistically significantly lower (p = 0.025 and 0.008, respectively) under timolol 0.1% gel treatment (QD) than with timolol 0.5% solution (BID).

Conclusions: The results indicate that the novel timolol 0.1% gel instilled QD is equivalent to timolol 0.5% solution instilled BID in reducing IOP in patients with POAG or OH. Both treatments were well tolerated with no statistically significant difference between the two groups. The lower timolol plasma levels with timolol 0.1% gel indicate a potential for fewer systemic undesirable effects in the treated population.