Bronchodilation of formoterol administered with budesonide: Device and formulation effects

Miller, C., Senn, S. and Mezzanotte, W. (2008) Bronchodilation of formoterol administered with budesonide: Device and formulation effects. Contemporary Clinical Trials, 29(2), pp. 114-124. (doi: 10.1016/j.cct.2007.05.008)

Abstract

BACKGROUND: Previous single-dose crossover studies have established therapeutic equivalence of formoterol when administered at the same nominal dose via a dry powder inhaler (DPI) or pressurized hydrofluoroalkane (HFA) metered-dose inhaler (pMDI). Demonstration of equivalent bronchodilation for formoterol administered as formoterol DPI or combined with budesonide in one pMDI (budesonide/formoterol pMDI) would indicate that the greater clinical efficacy of the budesonide/formoterol pMDI combination is due to the budesonide contribution and not to differences in formoterol formulation or delivery device. OBJECTIVE: To determine whether the formoterol-related bronchodilatory effects of formoterol DPI and budesonide/formoterol pMDI are similar, despite formoterol formulation and delivery device differences. METHODS: This was a multicenter, open-label, five-period crossover study conducted in 201 adult patients with stable asthma. The study included a screening visit, a 7- to 14-day run-in period, during which patients were treated with budesonide pMDI (80 mug per inhalation, two inhalations twice daily), and a randomized treatment period that included five single-day treatment periods, during which patients received single-dose crossover treatments, each of which was separated by a 3- to 14-day washout period. Patients were randomized to five of seven single-dose treatments (one, two, or four inhalations of budesonide/formoterol pMDI 80/4.5 mug; four inhalations of budesonide pMDI 80 mug plus one, two, or four inhalations of formoterol DPI 4.5 mug; or four inhalations of budesonide pMDI 80 mug alone). At clinic visits, the budesonide pMDI dose was coordinated with the budesonide dose delivered via the budesonide/formoterol pMDI such that all patients received a 320-mug dose of budesonide. The primary variable was average forced expiratory volume in 1 s (FEV(1)) from the area under the curve divided by time from 12-h serial spirometry. RESULTS: Average 12-h FEV(1) values were similar, regardless of delivery device, among treatments with the same nominal formoterol doses and dose-ordered within each device; mean FEV(1) values were significantly higher for treatments containing formoterol versus budesonide alone. The formoterol dose potency ratio for budesonide/formoterol pMDI:formoterol DPI (0.97; 95% confidence interval, 0.73-1.27) demonstrated clinical equivalence in bronchodilation at the same formoterol dose. CONCLUSION: Budesonide/formoterol pMDI affords equivalent formoterol-related bronchodilatory effects versus formoterol DPI at formoterol doses of 4.5, 9, and 18 mug, indicating that practitioners can expect and patients will experience similar bronchodilation from the same dose of formoterol whether it is delivered as monotherapy via a DPI or as combination therapy with budesonide via one pMDI.

• Item Type: Articles
• Keywords: incomplete blocks; cross-over trial; parallel assay; dose-finding;equivalence
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Senn, Professor Stephen
• Authors: Miller, C., Senn, S., and Mezzanotte, W.
• Subjects: R Medicine > RM Therapeutics. Pharmacology; Q Science > QA Mathematics
• College/School: College of Science and Engineering > School of Mathematics and Statistics > Statistics
• Journal Name: Contemporary Clinical Trials
• ISSN: 1551-7144