A dose-ranging study of tiotropium delivered via Respimat ^® Soft Mist ^TM Inhaler or HandiHaler ^® in COPD patients

Abstract

This was a multicenter, randomized, double-blind within device, parallel-group, dose-ranging study. COPD patients (n = 202; 86% male; mean age: 61 years) were randomized to receive tiotropium 1.25 μg, 2.5 μg, 5 μg, 10 μg, or 20 μg Respimat ^® SMI (a novel, propellant-free device); tiotropium 18 μg HandiHaler ^®; placebo Respimat ^®; or placebo HandiHaler ^® for 3 weeks. The primary endpoint was trough FEV ₁ on Day 21. Other assessments included FVC, PEFR, rescue medication use, safety, and pharmacokinetics. In general, all active treatments improved the primary and secondary endpoints on Day 21 (steady state) compared with placebo. Tiotropium 5 μg Respimat ^®, 20 μg Respimat ^®, and tiotropium 18 μg HandiHaler ^® were statistically significantly higher than placebo for the primary endpoint (mean change in trough FEV ₁ was 150 mL (both Respimat ^® doses) versus 20 mL (placebo Respimat ^®); p < 0.05; and 230 mL (HandiHaler ^®) versus −90 mL (placebo HandiHaler ^®); p ≤ 0.001). The urinary excretion (up to 2 hours post-dose) of tiotropium 5–10 μg Respimat ^® was comparable with tiotropium 18 μg HandiHaler ^®; the overall incidence of adverse events was comparable across treatment groups. Tiotropium 5 and 10 μg Respimat ^® improve lung function in COPD patients and appear to be comparable with tiotropium 18 μg HandiHaler ^®.