Effect of aclidinium bromide/formoterol fumarate fixed-dose combination on exacerbations in moderate-to-severe COPD: Pooled analysis of two studies

Background: Aclidinium/formoterol 400/12 µg fixed-dose combination (FDC) is in development for the treatment of COPD. We present pooled COPD exacerbation data from two Phase III studies.

Methods: ACLIFORM and AUGMENT were 24-week, randomized, double-blind Phase III studies of aclidinium/formoterol FDC in patients with moderate-to-severe COPD. Treatment arms were FDC 400/6 µg, FDC 400/12 µg, aclidinium 400 µg, formoterol 12 µg or placebo (all twice-daily via Genuair®/Pressair® inhaler). Prior exacerbation was not an inclusion criterion. Healthcare resource utilization (HCRU; symptom increase on ≥2 consecutive days requiring treatment change) and the EXAcerbations of Chronic pulmonary disease Tool (EXACT; increase ≥9 points for ≥3 days or ≥12 points for ≥2 days) were used to assess COPD exacerbations.

Results: The pooled population included 3398 patients (mean age 63.5 years, 60.5% male, 58.6% GOLD stage II, 40.8% stage III). Exacerbation rate was significantly reduced vs placebo following treatment with FDC 400/12 µg (moderate-severe HCRU by 29%; p < 0.05 and EXACT by 22%; p < 0.01). FDC 400/12 µg also resulted in delayed time to first exacerbation vs placebo (hazard ratio 0.70 [moderate-severe HCRU] and 0.79 [EXACT]; both p < 0.05).

Conclusions: Aclidinium/formoterol 400/12 µg FDC reduced the rate of both HCRU- and EXACT-defined COPD exacerbations in a study population where prior exacerbation was not an inclusion criterion.

Tab. 1: Annualized COPD exacerbation rates

*p < 0.05 vs placebo; **p < 0.01 vs placebo EXACT, EXAcerbations of Chronic pulmonary disease Tool; FDC, aclidinium bromide/formoterol fixed dose combination via the Genuair®/Pressair® multiple dose dry powder inhaler; HCRU, healthcare resource utilization. Genuair® and Pressair® are registered trademarks of Almirall S.A., Barcelona, Spain, for use within the United States as Pressair® and Genuair® within all other licensed territories
	Placebo (n = 526)	FDC 400/6 µg (n = 714)	FDC 400/12 µg (n = 720)
HCRU exacerbation rate (any)	0.47	0.36	0.36
Rate ratio vs placebo	-	0.77	0.76
HCRU exacerbation rate (moderate-severe)	0.42	0.33	0.29
Rate ratio vs placebo	-	0.79	0.71*
EXACT exacerbation rate	1.51	1.37	1.18
Rate ratio vs placebo	-	0.91	0.78**

Funding statement: This study was supported by Almirall S.A., Barcelona, Spain and Forest Laboratories LLC, a subsidiary of Actavis plc, New York, NY, USA.