Pharmacodynamic equivalence study of two preparations of eye drops containing dorzolamide and timolol in healthy volunteers

Abstract

Objective:

The aim of the present study was to assess the pharmacodynamic equivalence (lowering of intraocular pressure) of two preparations of eye drops containing 20 mg dorzolamide (CAS 120279-96-1) and 5 mg timolol (CAS 26839-75-8).

Method:

The study was conducted as a monocentric, observer-blinded, randomized, single-dose, two-period crossover study in 38 healthy volunteers. Each volunteer received on day 1 in each period in a random way a single dose of 1 drop of the test or the reference formulation in the conjunctival sac of the right eye separated by a wash-out period of 7 days. Measurement of intraocular pressure (IOP) of the right eye (by a blinded observer) was performed on day 1 of each study period pre-dose and 2 h post dosing by means of Goldmann applanation tonometry. In order to investigate the pharmacodynamic equivalence of both products, the two-sided 95% confidence interval was calculated for the difference of the primary target parameter (absolute decrease in IOP 2 h post dose), by means of a parametric (ANOVA) statistical method.

Results:

The results of the statistical evaluation of the primary target parameter “absolute decrease in IOP 2 h post dose” demonstrated a decrease in the IOP of 4.72 mmHg for the eye treated with the test formulation (dorzolamide 20 mg/ml + timolol 5 mg/ml eye drops) and 4.61 mmHg for the eye treated with the reference formulation. The mean difference was 0.11 mmHg. The 95% confidence interval was between −0.33 and 0.55 mmHg and thus entirely within the pre-defined equivalence range (± 1.5 mmHg). The results of the statistical evaluation of the secondary target parameter relative (as% of baseline) decrease in IOP 2 h post dose demonstrated essentially similar effectiveness in lowering the IOP by 27.63% (test formulation) and 27.12% (reference formulation), respectively. Both drug products were well tolerated.

Conclusion:

Both formulations showed comparable results obtained at a time probably equal to the maximum effect concerning the primary target parameter lowering of IOP 2 h post dose. The safety profile of both preparations showed no difference.

Key words

Crossover study design - Dorzolamide + timolol - Eye drops - Healthy volunteers - Pharmacodynamic equivalence

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