PURPOSE:To evaluate onset of bronchodilation with budesonide/formoterol pressurized metered-dose inhaler (pMDI) in chronic obstructive pulmonary disease (COPD) patients.
METHODS:Two randomized, double-blind, multicenter studies (Study I [6-month], NCT00206154; Study II [12-month], NCT00206167) were conducted in patients ≥40 years with moderate to very severe COPD. After 2 weeks of treatment based on previous therapy (inhaled corticosteroids and short-acting bronchodilators allowed), patients received budesonide/formoterol pMDI 160/4.5μg ×2 inhalations (320/9μg) (n=277 [I]; n=494 [II]), budesonide/formoterol pMDI 80/4.5μg ×2 inhalations (160/9μg) (n=281 [I]; n=494 [II]), budesonide pMDI 160μg ×2 inhalations (320μg) + formoterol dry powder inhaler (DPI) 4.5μg ×2 inhalations (9μg) (n=287 [I only]), budesonide pMDI 160μg ×2 inhalations (320μg) (n=275 [I only]), formoterol DPI 4.5μg ×2 inhalations (9μg) (n=284 [I]; n=495 [II]), or placebo (n=300 [I]; n=481 [II]), all twice daily. Time to achieve ≥15% improvement in FEV1 was assessed at randomization and treatment end.
RESULTS:Time to 15% FEV1 improvement was significantly (P<.001; Wilcoxon test) earlier for budesonide/formoterol (both doses) and formoterol versus placebo in both studies and for budesonide/formoterol (both doses) versus budesonide (assessed in study I only). Median time (minutes) to 15% FEV1 improvement was as follows: budesonide/formoterol 320/9μg (6.8 [I]; 4.2 [II]), budesonide/formoterol 160/9μg (4.9 [I]; 4.8 [II]), budesonide + formoterol (6.2 [I]), and formoterol (9.0 [I]; 6.0 [II]). The percentages of patients achieving ≥15% FEV1 improvement within 15 minutes postdose were as follows: budesonide/formoterol 320/9μg (58.6% [I]; 72.7% [II]), budesonide/formoterol 160/9μg (60.8% [I]; 70.2% [II]), budesonide + formoterol (60.7% [I]), budesonide (19.8% [I]), formoterol (61.5% [I]; 60.5% [II]), and placebo (13.0% [I]; 13.6% [II]). Onset of bronchodilation for budesonide/formoterol was similar at treatment end.
CONCLUSION:Budesonide/formoterol pMDI (both doses) demonstrated a rapid bronchodilatory effect that was faster than that of budesonide and placebo and similar to formoterol DPI and budesonide pMDI + formoterol DPI in moderate to very severe COPD patients.
CLINICAL IMPLICATIONS:Clinical benefits of statistically significant bronchodilation within 4–7 minutes with budesonide/formoterol pMDI may include rapid symptom control, which may positively impact treatment adherence.
DISCLOSURE:Harold Nelson, University grant monies Dr. Tashkin: AstraZeneca grants to Regents of the University of California: 6-month RCT of Symbicort pMDI in COPD ($7,136) and 1-year RCT of Symbicort pMDI in Hispanic-American patients with asthma ($4,841.27); Grant monies (from industry related sources) Dr. Nelson: Schering-Plough, TEVA, Critical Therapeutics, Wyeth, Altana, Boehringer-Ingelheim, Novartis, AstraZeneca, Sepracor, Genentech. Dr. Rennard: Almirall, Centocor, GlaxoSmithKline, IFSH, Lorillard, Novartis, Philip Morris, Roche; Shareholder Ms. Martin and Dr. Goldman: AstraZeneca; Employee Ms. Martin and Drs. Goldman and Silkoff: AstraZeneca; Consultant fee, speaker bureau, advisory committee, etc. Dr. Nelson: Genentech/Novartis, Curalogic, GlaxoSmithKline, Schering-Plough, Astellas, Ception, Boehringer-Ingelheim, AstraZeneca, Dey Laboratories, Dynavax Technologies, Abbott Laboratories, MediciNova, Johnson & Johnson, VentiRx, Dyson. Dr. Rennard: Abbott, Adams, Almirall, Altana, Anthera, AstraZeneca, GlaxoSmithKline, Johnson & Johnson, Novartis, Pfizer, Quintiles, Roche, TareGen. Dr. Tashkin: AstraZeneca; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Budesonide/formoterol pMDI is not approved for use in patients with COPD.