Efficacy and tolerability of budesonide formoterol in one hydrofluoroalkane pressurized metered-dose inhaler in patients with chronic obstructive pulmonary disease: Results from a 1-year randomized controlled clinical trial

Abstract

Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations. The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study andwhen administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study. Objective: This study assessed the long-termefficacy and tolerability of budesonide/ formoterol HFA pMDI in patients with moderate to very severe COPD. Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel- group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged 40 yearswithmoderate to very severeCOPDconducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico. After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodi tors allowed), patients received one of the following treatments twice daily: budesonide/formoterol pMDI 160/4.5 mg two inhalations (320/9 mg); budesonide/formoterol pMDI 80/4.5 mg two inhalations (160/9 mg); formoterol DPI 4.5 mg two inhalations (9 mg); or placebo. Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1.Results: Budesonide/formoterol 320/9 mg demonstrated greater improvements in pre-dose FEV1 versus formoterol (p = 0.008), and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001). The rate of COPDexacerbations was lower in both budesonide/ formoterol groups compared with formoterol and placebo (p 0.004). Both budesonide/formoterol doses were more effective than placebo (p 0.006) for controlling dyspnoea and improving health status (St George's RespiratoryQuestionnaire). All treatments were generally well tolerated. The incidence of pn umonia was not different for active (3.4-4.0%) and placebo (5.0%) groups. Conclusions: Budesonide/formoterol pMDI (320/9 mg and 160/9 mg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD. Only budesonide/formoterol pMDI 320/9 mg demonstrated greater efficacy for both co-primary variables compared with formoterol DPI 9 mg. Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo. © 2009 Adis Data Information BV.