Pharmacodynamic approach for proving equivalence of two ophtalmic solutions containing Brimonidine Tartarate 0.2% in healthy volunteers

Introduction: Bromonidine tartarate ophthalmic solution (CAS registry-number: 70359- 46-5) is a relatively selective alpha-2 adrenergic agonist, indicated for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Aim: The purpose of the present phase-1 clinical trial was to assess the pharmacodynamic equivalence of two ophtalmic solutions containing brimonidine tartarate 0,2% in healthy volunteers. Methods: The study was performed as a single center, randomized, single-dose, observer-blinded, single period trial in 36 healthy volunteers. Each volunteer received successively and in a random way a single dose of 1 drop of the test or the reference product in the conjunctival sac of the right and left eye, respectively. Measurement of intraocular pressure (IOP) of both eyes was performed at screening examination, pre-dose and 2 hours post dosing and at final examination by means of a Goldmann applanation tonometer. The primary target parameter for proving pharmacodynamic equivalence was defined as the absolute decrease in IOP 2 hours post dose. The 95% confidence interval was calculated for the difference (test-reference) of the primary target parameter and compared with the predefined equivalence range of ±1.5 mmHg. Results: A decrease in the IOP of 4.60±1.26 mmHg and 4.40±0.89 mmHg was observed after administration of the test and reference formulation, respectively. The mean difference was +0.197 mmHg with a 95% confidence interval between -0.275 and 0.670 mmHg and thus entirely within the predefined equivalence range. Both products showed a very good local safety profile and similar tolerability. Conclusion: Brimonidine Tartrate Ophthalmic Solution 0.2% was pharmacodynamically equivalent to the reference preparation (Alphagan®) with respect both to efficacy and safety.