Non–Inferiority, in the Intra–Ocular Pressure (IOP)–Lowering Effect, of a New Eye–Drops Formulation of 0.5% Timolol (Timolast(tm)) Instilled Once–Daily versus 0.5%Timoptol®, Instilled Twice–Daily, for 4 Months in Ocular Hypertensive or Glaucomatous Patients"

Abstract

Abstract: : Purpose: To demonstrate that the trough IOP–lowering effect of 0.5% Timolast, once daily was non–inferior to that of 0.5% Timoptol^®, twice daily, after 4 months of treatment in patients with POAG or ocular hypertension. Methods: Phase III, multicentre, double–masked, randomised, crossover, non–inferiority study. 57 patients were randomly allocated to one of the 2 sequence groups in order to receive 0.5% Timolast, morning / Timolast vehicle, evening, during one period and 0.5% Timoptol^®, morning and evening, during the other period. IOP assessment was performed, for each period, at the following visits: Day 0, Day 28, Day 70, Day 112. The primary efficacy variable was the morning trough IOP, before instillation of the study product, following 4 months of treatment. Non–inferiority testing was performed by calculating the 2–sided 95% confidence interval (CI) on the mean difference between the two study products, and comparing the upper limit of this interval with the non–inferiority margin (1.5 mmHg). Secondary efficacy IOP criteria, safety were also evaluated. Results: The primary efficacy analysis was performed in the PP population and confirmed in the ITT population. The mean ± SD IOP on Day 112, in the selected eye, was 15.6 ± 2.5 mmHg under 0.5% Timolast versus 15.4 ± 2.4 mmHg under 0.5% Timoptol^®. The estimated mean of the difference (0.5% Timolast minus 0.5% Timoptol^®) was 0.422 mmHg (including the factors centre and centre/treatment interaction). The 2–sided 95% CI on the estimated mean difference between the 2 study products was [–0.121 mmHg; 0.964 mmHg]. The upper limit of this interval was less than the non–inferiority margin (1.5 mmHg), thus, 0.5% Timolast was non–inferior than 0.5% Timoptol^®. Regarding IOP second efficacy criteria, there were no differences between the 2 products. Conclusions: Statistical analysis of the primary efficacy variable, showed that 0.5% Timolast, once daily, was non–inferior to 0.5% Timoptol^®, twice daily, in its IOP–controlling effect, after a 4 month treatment period. Statistical analysis of the secondary IOP efficacy variables demonstrated that there were no significant differences between the 2 products. Global local and objective ocular tolerances were good with both products. Systemic tolerance appeared to be better under 0.5% Timolast.

Keywords: clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • pharmacology