Effects of aclidinium bromide/formoterol fumarate fixed-dose combination on health status in COPD

Background: Aclidinium/formoterol fixed-dose combination (FDC) is in development for the treatment of COPD. We investigated the effect of the FDC on the health status of patients with moderate-to-severe COPD.

Methods: ACLIFORM and AUGMENT were 24-week, randomized, double-blind Phase III studies of twice-daily FDC. Patients received placebo, aclidinium 400 µg, formoterol 12 µg, FDC 400/6 µg, or FDC 400/12 µg. Endpoints were change in St George's Respiratory Questionnaire (SGRQ) total score at Week 24 vs baseline and percentage of patients improving by ≥4 units (the minimum clinically important difference [MCID]).

Results: The ITT populations comprised 1726 patients (mean age 63.2 years; 67.6% male; moderate COPD 60.1%; mean baseline SGRQ score 46.2) for ACLIFORM and 1668 (mean age 63.9 years; 53.2% male; moderate COPD 57.0%; mean baseline SGRQ score 46.0) in AUGMENT.

SGRQ total score increased by ≥MCID at Week 24 for FDC 400/6 µg and 400/12 µg in both studies (Table). Over half of patients receiving the FDC achieved or exceeded the MCID. In ACLIFORM, improvements in SGRQ total score with the FDC did not reach significance versus placebo, possibly due to a very large placebo response (>MCID).

Conclusions: Aclidinium/formoterol FDC resulted in improved health status in patients with moderate-to-severe COPD, notwithstanding the large placebo effect that may have masked the treatment effect in ACLIFORM.

Tab. 1: Change from baseline in health status at Week 24 (ITT population)

	Placebo	FDC 400/12 µg	FDC 400/6 µg	Aclidinium 400 µg	Formoterol 12 µg
ACLIFORM	n = 194	n = 385	n = 381	n = 383	n = 383
LS mean SGRQ scorea	-6.5	-7.2	-8.3	-5.8	-5.6
Treatment difference vs placebo		-0.7	-1.8	0.7	0.9
Patients achieving or exceeding MCID, %	53.2	55.3	64.2	53.5	52.1
Odds ratio vs placebo		1.1	1.8*†	1.0	1.0
AUGMENT	n = 331	n = 335	n = 333	n = 337	n = 332
LS mean SGRQ scorea	-2.2	-6.6	-5.9	-6.4	-4.7
Treatment difference vs placebo		-4.4****	-3.7***	-4.2****	-2.5*
Patients achieving or exceeding MCID, %	38.7	58.2	53.6	54.5	52.4
Odds ratio vs placebo		2.3***	2.1**	2.2**	1.9**
*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 vs placebo; †p < 0.05 vs FDC 400/12 µg aLower values represent greater improvement FDC, aclidinium/formoterol fixed-dose combination; ITT, intent-to-treat; LS, least squares; MCID, minimum clinically important difference (≥ 4 units); SGRQ, St George's Respiratory Questionnaire

Funding:

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