Methacholine challenge tests to demonstrate therapeutic equivalence of terbutaline sulfate via different Turbuhaler® devices in patients with mild to moderate asthma: Appraisal of a four-way crossover design
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Background/Objective To demonstrate therapeutic equivalence of terbutaline via two different Turbuhaler® 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® M2 or Turbuhaler® 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® M3 and M2, respectively (both p < 0.001). The between-device ratios (M3:M2) were 0.92 (95% CI: 0.75–1.13) for 0.5 mg and 0.88 (95% CI 0.72–1.08) for 1.5 mg. Both confidence intervals lie inside the interval 0.67–1.50, which was the pre-specified condition for equivalent effect. Conclusions Bronchoprotection using a standardised methacholine challenge model proved to be an effective design to elucidate therapeutic equivalence between devices in patients with mild-to-moderate asthma. The findings indicate that patients may switch from one type of Turbuhaler® to the other without adjustment of therapy. Moreover, they show the robustness and utility of this study design and its suitability for investigating therapeutic equivalence. EudraCT Number 2014-001457-16. Clinicaltrials.gov identifier NCT02322788.
|Enheter & grupper|
Ämnesklassifikation (UKÄ) – OBLIGATORISK
|Tidskrift||Pulmonary Pharmacology and Therapeutics|
|Status||Published - 2017 jun 1|
|Peer review utförd||Ja|