One-Year Extension Study of ACCORD COPD I: Safety and Efficacy of Two Doses of Twice-daily Aclidinium Bromide in Patients with COPD

Figures & data

Figure 1.  Study Flow Chart. ITT = intent to treat.

Table 1.  Demographic and baseline characteristics of patients in the extension study^a

	Treatment Sequence
	Aclidinium 200 μg			Aclidinium 400 μg
	Prior treatment in lead-in study			Prior treatment in lead-in study
Characteristic	Placebo n = 44	Aclidinium 200 μg n = 93	Total n = 137	Placebo n = 46	Aclidinium 400 μg n = 106	Total n = 152	Total N = 289
Age, mean (SD), years	65.0 (11.4)	62.5 (9.4)	63.3 (10.1)	65.0 (9.1)	64.1 (10.0)	64.4 (9.7)	63.9 (9.9)
Male, n (%)	23 (52.3)	51 (54.8)	74 (54.0)	24 (52.2)	52 (49.1)	76 (50.0)	150 (51.9)
Caucasian, n (%)	42 (95.5)	83 (89.2)	125 (91.2)	44 (95.7)	101 (95.3)	145 (95.4)	270 (93.4)
BMI, mean (SD), kg/m^2	27.8 (5.1)	27.6 (5.2)	27.7 (5.2)	27.5 (5.2)	27.0 (4.9)	27.1 (5.0)	27.4 (5.1)
Current smoker, n (%)	19 (43.2)	42 (45.2)	61 (44.5)	19 (41.3)	47 (44.3)	66 (43.4)	127 (43.9)
Smoking history, mean (SD), pack-years	50.4 (31.6)	52.5 (24.0)	51.8 (26.6)	54.7 (31.8)	57.1 (29.5)	56.4 (30.1)	54.2 (28.6)
Postbronchodilator FEV1, mean (SD),% of predicted value	60.1 (12.9)	52.2 (13.2)	54.8 (13.6)	53.2 (13.8)	53.7 (12.7)	53.6 (13.0)	54.1 (13.3)
Postbronchodilator FEV1/FVC, mean (SD),%	56.6 (11.0)	52.1 (9.9)	53.5 (10.4)	53.3 (10.0)	51.7 (9.7)	52.2 (9.8)	52.8 (10.1)
Bronchial reversibility,^b mean (SD),%	11.8 (13.7)	16.7 (15.9)	15.1 (15.4)	16.7 (11.8)	14.0 (12.3)	14.9 (12.2)	15.0 (13.7)
Baseline FEV1,^c mean (SD), L	1.51 (0.53)	1.30 (0.51)	1.37 (0.52)	1.33 (0.58)	1.31 (0.47)	1.31 (0.51)	1.34 (0.52)
SGRQ total score, ^c mean (SD)	38.4 (14.9)	43.8 (17.6)	42.0 (16.9)	44.6 (17.7)	47.0 (16.3)	46.3 (16.7)	44.3 (16.9)
Rescue medication use, ^c mean (SD), puffs/day	3.6 (3.3)	3.8 (3.3)	3.8 (3.3)	3.7 (4.4)	4.4 (5.4)	4.2 (5.1)	4.0 (4.3)

^aSafety population at Visit 1 (enrollment) of the lead-in study unless otherwise indicated; ^bcalculated as% change = 100 x (postbronchodilator FEV₁)-(prebronchodilator FEV₁)/(prebronchodilator FEV₁); ^cIntent-to-treat population at Visit 2 (randomization) of the lead-in study; BMI, body mass index; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; SD, standard deviation, SGRQ, St. George's Respiratory Questionnaire.

Table 2.  Treatment-emergent adverse events (TEAEs) reported by ≥2% of total patients (number [%]; safety population)

	Aclidinium 200 μg			Aclidinium 400 μg
	Prior treatment in lead-in study			Prior treatment in lead-in study
Preferred Term	Placebo n = 44	Aclidinium 200 μg n = 93	Total n = 137	Placebo n = 46	Aclidinium 400 μg n = 106	Total n = 152	Total N = 289
At least 1 TEAE	35 (79.5)	71 (76.3)	106 (77.4)	35 (76.1)	77 (72.6)	112 (73.7)	218 (75.4)
COPD exacerbation	13 (29.5)	22 (23.7)	35 (25.5)	12 (26.1)	21 (19.8)	33 (21.7)	68 (23.5)
Nasopharyngitis	4 (9.1)	5 (5.4)	9 (6.6)	2 (4.3)	10 (9.4)	12 (7.9)	21 (7.3)
Upper respiratory tract infection	3 (6.8)	6 (6.5)	9 (6.6)	2 (4.3)	6 (5.7)	8 (5.3)	17 (5.9)
Urinary tract infection*	2 (4.5)	3 (3.2)	5 (3.6)	2 (4.3)	7 (6.6)	9 (5.9)	14 (4.8)
Sinusitis	4 (9.1)	6 (6.5)	10 (7.3)	1 (2.2)	3 (2.8)	4 (2.6)	14 (4.8)
Arthralgia	2 (4.5)	5 (5.4)	7 (5.1)	2 (4.3)	3 (2.8)	5 (3.3)	12 (4.2)
Back pain	2 (4.5)	5 (5.4)	7 (5.1)	0 (0)	4 (3.8)	4 (2.6)	11 (3.8)
Cough	0 (0)	5 (5.4)	5 (3.6)	3 (6.5)	2 (1.9)	5 (3.3)	10 (3.5)
Contusion	0 (0)	4 (4.3)	4 (2.9)	4 (8.7)	1 (0.9)	5 (3.3)	9 (3.1)
Dyspnea	0 (0)	5 (5.4)	5 (3.6)	2 (4.3)	2 (1.9)	4 (2.6)	9 (3.1)
Blood glucose increased	3 (6.8)	3 (3.2)	6 (4.4)	3 (6.5)	0 (0)	3 (2.0)	9 (3.1)
Left bundle branch block	3 (6.8)	3 (3.2)	6 (4.4)	0 (0)	3 (2.8)	3 (2.0)	9 (3.1)
Hypertension	2 (4.5)	4 (4.3)	6 (4.4)	0 (0)	3 (2.8)	3 (2.0)	9 (3.1)
Pneumonia	3 (6.8)	3 (3.2)	6 (4.4)	1 (2.2)	2 (1.9)	3 (2.0)	9 (3.1)
Edema peripheral	0 (0)	3 (3.2)	3 (2.2)	2 (4.3)	3 (2.8)	5 (3.3)	8 (2.8)
Rash	1 (2.3)	2 (2.2)	3 (2.2)	0 (0)	5 (4.7)	5 (3.3)	8 (2.8)
Headache	1 (2.3)	3 (3.2)	4 (2.9)	1 (2.2)	3 (2.8)	4 (2.6)	8 (2.8)
Increased gamma-glutamyltransferase	2 (4.5)	3 (3.2)	5 (3.6)	1 (2.2)	2 (1.9)	3 (2.0)	8 (2.8)
Fall	0 (0)	4 (4.3)	4 (2.9)	2 (4.3)	1 (0.9)	3 (2.0)	7 (2.4)
Bronchitis	0 (0)	1 (1.1)	1 (0.7)	1 (2.2)	4 (3.8)	5 (3.3)	6 (2.1)
Anxiety	0 (0)	3 (3.2)	3 (2.2)	0 (0)	3 (2.8)	3 (2.0)	6 (2.1)
Cystitis	1 (2.3)	2 (2.2)	3 (2.2)	0 (0)	3 (2.8)	3 (2.0)	6 (2.1)
Constipation*	2 (4.5)	2 (2.2)	4 (2.9)	0 (0)	2 (1.9)	2 (1.3)	6 (2.1)

Data reported as number (%); *AEs typically reported with LAMA treatment.

Table 3.  Treatment-emergent cardiac adverse events reported by ≥2 patients in the total population (number [%]; safety population)

	Aclidinium 200 μg			Aclidinium 400 μg
	Prior treatment in lead-in study			Prior treatment in lead-in study
Preferred term	Placebo n = 44	Aclidinium 200 μg n = 93	Total n = 137	Placebo n = 46	Aclidinium 400 μg n = 106	Total n = 152	Total N = 289
Any cardiac TEAE	6 (13.6)	10 (10.8)	16 (11.7)	1 (2.2)	9 (8.5)	10 (6.6)	26 (9.0)
Left/right bundle branch block	3 (6.8)	5 (5.4)	8 (5.8)	0 (0)	3 (2.8)	3 (2.0)	11 (3.8)
Atrioventricular block first degree	1 (2.3)	2 (2.2)	3 (2.2)	1 (2.2)	1 (0.9)	2 (1.3)	5 (1.7)
Coronary artery disease	1 (2.3)	0	1 (0.7)	0	1 (0.9)	1 (0.7)	2 (0.7)
Congestive cardiac failure	2 (4.5)	0	2 (1.5)	0	1 (0.9)	1 (0.7)	3 (1.0)
Ventricular extrasystoles	1 (2.3)	1 (1.1)	2 (1.5)	0	0	0	2 (0.7)

Figure 2.  Least squares mean (SE) change from baseline in trough FEV₁ in patients on continuous aclidinium treatment (A) or switched from placebo to aclidinium (B).

Figure 3.  Least squares mean (SE) change from baseline in peak FEV₁ in patients on continuous aclidinium treatment (A) or switched from placebo to aclidinium (B).

Figure 4.  Least squares mean (SE) change from baseline in SGRQ total score in patients on continuous aclidinium treatment (A) or switched from placebo to aclidinium (B).