Methacholine challenge tests to demonstrate therapeutic equivalence of terbutaline sulfate via different Turbuhaler (R) devices in patients with mild to moderate asthma: Appraisal of a four-way crossover design

Background/Objective: To demonstrate therapeutic equivalence of terbutaline via two different Turbuhaler((R)) devices by evaluating its protective effect against methacholine-induced bronchoconstriction in stable asthma. Methods: In this double-blind, double-dummy, multicentre, single-dose, 4-way crossover study, patients with stable mild-to-moderate asthma (FEV1 >= 80% predicted) were randomised to 0.5 or 1.5 mg terbutaline via either Turbuhaler((R)) M2 or Turbuhaler((R)) M3 followed by a methacholine challenge test. The primary outcome variable was the concentration of methacholine causing a 20% drop in FEV1 (PC20). Patients had a PC20 methacholine <8 mg/mL that was reproducible after 2 weeks, and a stable baseline FEV1 at all visits (90-110% of enrolment value). Results: 60 patients (mean age 31.1 years [range:18-64]; mean FEV1 92.1% predicted normal [78.4 -120.6%]) were randomised to treatment; all completed the study. There was a clear dose-response for both devices. The within-device ratios (1.5 mg:0.5 mg) were 1.79 and 1.87 for Turbuhaler((R)) M3 and M2, respectively (both p