Improvement in 24-hour bronchodilation and symptom control with aclidinium bromide versus tiotropium and placebo in symptomatic patients with COPD: post hoc analysis of a Phase IIIb study

Figures & data

Figure 1 Patient flow diagram.

Abbreviations: AE, adverse event; BID, twice daily; E-RS, Evaluating Respiratory Symptoms; QD, once daily.

Table 1 Patient demographics in symptomatic patients (E-RS baseline score ≥10 units)

	Placebo (N=60)	Aclidinium 400 µg BID (N=116)	Tiotropium 18 µg QD (N=101)
Gender (male), n (%)	35 (58.3)	75 (64.7)	70 (69.3)
Age (years), mean (SD)	62.1 (8.2)	61.4 (8.4)	62.9 (8.1)
Race, n (%)
White	59 (98.3)	116 (100)	101 (100)
BMI (kg/m^2), mean (SD)	26.8 (5.4)	27.4 (4.9)	27.1 (4.8)
Current smoker, n (%)	31 (51.7)	64 (55.2)	56 (55.5)
Smoking consumption (pack-years), mean (SD)	38.8 (14.3)	41.7 (23.7)	42.4 (17.1)
COPD duration (years), mean (SD)	9.63 (6.7)	8.44 (5.8)	8.44 (6.6)
Post-bronchodilator FEV1 (L)
Mean (SD)	1.56 (0.54)	1.59 (0.50)	1.53 (0.49)
% predicted, mean (SD)	55.2 (12.1)	55.5 (13.4)	53.0 (13.1)
Mean bronchial reversibility, % (SD)	10.1 (9.7)	14.7 (15.2)	10.8 (12.8)
COPD severity,a n (%)
Moderate	40 (66.7)	72 (62.1)	56 (56.0)
Severe	20 (33.3)	44 (37.9)	44 (44.0)
Exacerbations in previous year, n (%)
0	46 (76.7)	75 (64.7)	67 (66.3)
1	12 (20.0)	31 (26.7)	30 (29.7)
≥2	2 (3.3)	10 (8.6)	4 (4.0)
E-RS Total score (SD)	16.2 (4.3)	16.4 (4.2)	15.8 (3.8)
E-RS Cough and Sputum (SD)	4.3 (1.6)	4.5 (1.4)	4.4 (1.1)
E-RS Chest Symptoms (SD)	3.9 (1.3)	4.0 (1.4)	3.7 (1.3)
E-RS Breathlessness (SD)	8.0 (2.5)	7.9 (2.5)	7.7 (2.5)
Severity of early-morning symptoms
Any (SD)	2.5 (0.5)	2.6 (0.5)	2.5 (0.5)
Cough (SD)	1.4 (0.8)	1.5 (0.7)	1.4 (0.7)
Wheeze (SD)	0.9 (0.9)	0.9 (0.8)	0.8 (0.7)
Shortness of breath (SD)	1.3 (0.7)	1.3 (0.8)	1.1 (0.8)
Phlegm (SD)	0.8 (0.9)	1.1 (0.9)	0.9 (0.9)
Limitation of activity (SD)	2.3 (0.6)	2.3 (0.6)	2.3 (0.7)
Severity of nighttime symptoms (SD)	2.1 (0.7)	2.2 (0.6)	2.1 (0.6)

Notes:

a GOLD stage II (moderate): FEV₁/FVC <0.70, and post-bronchodilator FEV₁ ≥50% and <80% predicted; GOLD stage III (severe): FEV₁/FVC <0.70, and post-bronchodilator FEV₁ ≥30% and <50% predicted.

Abbreviations: BID, twice daily; BMI, body mass index; E-RS, Evaluating Respiratory Symptoms; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global initiative for chronic Obstructive Lung Disease; QD, once daily; SD, standard deviation.

Figure 2 Symptomatic patients: mean changes from baseline in FEV₁ at week 6 over 24 hours.

Notes: Placebo N=60, aclidinium 400 μg N=116, tiotropium 18 μg N=101. *P<0.05 versus tiotropium; P<0.05 for aclidinium 400 μg versus placebo and tiotropium 18 μg versus placebo at all time points, except aclidinium at 10 hours (P=0.08) and tiotropium at 23 hours (P=0.14).
Abbreviations: FEV₁, forced expiratory volume in 1 second; LS, least squares.

Figure 3 Symptomatic patients: change from baseline in trough FEV₁ versus placebo at day 1 and week 6.

Notes: Placebo N=60, aclidinium 400 μg N=116, tiotropium 18 μg N=101. *P<0.05, ***P<0.001 versus placebo; ^#P<0.05 versus tiotropium.
Abbreviations: FEV₁, forced expiratory volume in 1 second; LS, least squares.

Figure 4 Symptomatic patients: change from baseline in E-RS Total and domain symptom scores versus placebo (A) and percentage of E-RS responders (B) at week 6.

Notes: Percentage reduction is shown in brackets. Placebo N=60, aclidinium 400 μg N=116, tiotropium 18 μg N=101. *P<0.05, **P<0.01, ***P<0.001 versus placebo; ^#P<0.05 versus tiotropium. Scores: 0–40 for Total, 0–17 for Breathlessness, 0–12 for Chest Symptoms, 0–11 for Cough and Sputum.
Abbreviations: E-RS, Evaluating Respiratory Symptoms; LS, least squares; OR, odds ratio.

Figure 5 Symptomatic patients: change from baseline in symptom severity in the early morning (A) and nighttime (B), and limitation of early-morning activity (C) over 6 weeks.

Notes: Percentage reduction is shown in brackets. Placebo N=60, aclidinium 400 μg N=116, tiotropium 18 μg N=101. *P<0.05, **P<0.01 versus placebo; ^#P<0.05 versus tiotropium. Specific symptoms (A): 1= mild, 2= moderate, 3= severe, 4= very severe; any symptom: 1= no symptoms, 2= mild, 3= moderate, 4= severe, 5= very severe. For patients with no symptom, a zero value was assigned. Nighttime symptom severity (B): 1= mild, 2= moderate, 3= severe, 4= very severe. Limitation of activity (C): 1= not at all, 2= a little, 3= moderately, 4= a good deal, 5= a very good deal.
Abbreviation: LS, least squares.