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
