Pharmacokinetics and tolerability (Study 1) with particular reference to ocular safety (Study 2) of tiotropium Respimat^® Soft Mist™ Inhaler: findings from two dose-ranging studies in healthy men

Ulrich Feifel¹, Gudrun Wallenstein¹, Karl-Ludwig Rominger¹, Dirk Trommeshauser², Juliane Platz²

¹Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216 Ingelheim, Germany; ²Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorf Straße 65, 88397 Biberach, Germany

Abstract: Data are presented from two randomized, double-blind, placebo-controlled studies in which the tolerability of tiotropium Respimat^® Soft Mist™ Inhaler (SMI), a new-generation, propellant-free device for use in COPD, and the ocular safety of tiotropium were examined. In Study 1, 36 healthy males received tiotropium 8, 16, or 32 µg (n = 9/dose) or placebo (n = 3/dose level), administered once daily via Respimat^® SMI for 14 days. Safety and pharmacokinetics were evaluated. In Study 2, 48 healthy males received tiotropium 0.02, 0.04, 0.08, 0.16, 0.28, or 0.40 µg (n = 6/dose) or placebo (n = 2/dose level), applied as two drops to one eye (the highest dose was a significant multiple of a percentage of the proposed Respimat^® SMI clinical dose that could be inadvertently deposited in the eye). Ocular parameters were measured over 24 hours. Tiotropium Respimat^® SMI at doses up to 32 µg was well tolerated in Study 1; typical dose-dependent anticholinergic adverse events of mild-to-moderate intensity were observed. In Study 2, ocular tiotropium administration did not affect pupil diameter, pupillary reflex, intraocular pressure, or accommodation. Tiotropium Respimat^® SMI was well tolerated. Inadvertent ocular exposure to tiotropium up to 0.40 µg is unlikely to result in ocular adverse effects.

Keywords: Respimat^® Soft Mist™ Inhaler, tiotropium, anticholinergic, chronic obstructive pulmonary disease