Efficacy and Safety of Once-Daily Inhaled Umeclidinium in Asian Patients with COPD: Results from a Randomized, Placebo-Controlled Study

Figures & data

Table 1 Patient Demographics and Baseline Characteristics

	Placebo	UMEC
n	101	205
Mean age, years (SD)	65.7 (7.05)	65.5 (6.89)
Male, n (%)	97 (96)	193 (94)
Current smoker at screening, n (%)	29 (29)	64 (31)
Mean smoking pack-years (SD)	37.2 (18.80)	36.8 (16.72)
ICS use at screening, n (%)	48 (48)	100 (49)
Mean mMRC dyspnea score (SD)	2.2 (0.37)	2.2 (0.49)
COPD exacerbations in the 12 months prior to pre-screening, n (%)
Moderate (required oral/systemic corticosteroids and/or antibiotics)
0	79 (78)	156 (76)
1	17 (17)	34 (17)
2	3 (3)	10 (5)
≥3	2 (2)	4 (2)
Severe (required hospitalization)
0	87 (86)	189 (92)
1	12 (12)	14 (7)
2	0	2 (<1)
>2	2 (2)	0
Mean baseline FEV1, mL (SD)	1016 (331)	1042 (371)^a
Mean % predicted FEV1 post-albuterol, % (SD)	47.32 (12.52)	48.88 (13.61)
GOLD stage (% predicted FEV1), n (%)
Stage I (≥80%)	0	0
Stage II (≥50% to <80%)	44 (44)	100 (49)
Stage III (≥30% to <50%)	46 (46)	86 (42)
Stage IV (<30%)	11 (11)	19 (9)
Mean BDI focal score (SD)	6.7 (2.30)	6.6 (2.36)

Note: ^aN=204.

Abbreviations: BDI, Baseline Dyspnea Index; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 s; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; mMRC, modified Medical Research Council; SD, standard deviation; UMEC, umeclidinium.

Figure 1 Patient disposition.

Abbreviations: mITT, modified intent-to-treat; UMEC, umeclidinium.

Table 2 Lung Function Endpoints

	Placebo	UMEC
CFB in Trough FEV1 at Day 169
n	80	176
LS mean change, mL (SE)	−22 (17)	131 (12)
Treatment difference vs placebo, mL (95% CI)  p-value	–	154 (113, 194) <0.001
Weighted Mean FEV1 Over 0–6 hrs on Day 1
n	101	203
LS mean FEV1, mL (SE)	1047 (9)	1172 (6)
LS mean CFB FEV1, mL (SE)	11 (9)	136 (6)
Treatment difference vs placebo, mL (95% CI)  p-value	–	125 (103, 147) p<0.001
Serial Mean FEV1 Over 0–6 hrs on Day 1
n	101	203
LS mean FEV1, mL (SE)	1029 (11)	1166 (8)
LS mean CFB FEV1, mL (SE)	−4 (11)	132 (8)
Treatment difference vs placebo, mL (95% CI)  p-value	–	136 (109, 164) p<0.001
Serial Mean FVC Over 0–6 hrs on Day 1
n	101	203
LS mean FVC, mL (SE)	2680 (28)	2922 (20)
LS mean CFB FVC, mL (SE)	4 (28)	284 (20)
Treatment difference vs placebo, mL (95% CI)  p-value	–	242 (175, 310) p<0.001

Abbreviations: CFB, change from baseline; CI, confidence interval; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; LS, least squares; SE, standard error; UMEC, umeclidinium.

Figure 2 Change from baseline in (A) trough FEV₁ and (B) trough FVC.

Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; LS, least squares; UMEC, umeclidinium.

Figure 3 TDI focal score at Days 28, 84, and 168.

Abbreviations: CI, confidence interval; LS, least squares; TDI, Transient Dyspnea Index; UMEC, umeclidinium.

Table 3 Proportion of TDI Responders (Defined as a TDI Focal Score ≥1 Unit)

TDI Response	Placebo N=101	UMEC N=205
Day 28, n	94	199
Responders, n (%)	52 (55)	133 (67)
UMEC vs placebo odds ratio (95% CI) p-value	–	1.7 (1.0, 2.8) p=0.057
Day 84, n	94	198
Responders, n (%)	54 (57)	134 (68)
UMEC vs placebo odds ratio (95% CI) p-value	–	1.6 (0.9, 2.7) p=0.078
Day 168, n	94	199
Responders, n (%)	47 (50)	132 (66)
UMEC vs placebo odds ratio (95% CI) p-value	–	2.0 (1.2, 3.4) p=0.007

Abbreviations: CI, confidence interval; TDI, Transition Dyspnea Index; UMEC, umeclidinium.

Table 4 Rescue Medication Use, Mean SGRQ Total Score and CAT Score

	Placebo N=101	UMEC N=205
Rescue Medication Use
Weeks 1–24, n	86	177
LS mean number of puffs of rescue medication per day (SE)	1.7 (0.16)	1.2 (0.11)
LS mean CFB in number of puffs of rescue medication per day (SE)	0.1 (0.16)	−0.4 (0.11)
Treatment difference vs placebo, number (95% CI)  p-value	–	−0.5 (−0.9, −0.1) p=0.008
SGRQ Total Score
Day 28, n	91	188
LS mean total score (SE)	40.01 (1.174)	35.62 (0.813)
LS mean CFB (SE)	−1.45 (1.174)	−5.84 (0.813)
Treatment difference vs placebo, number (95% CI)  p-value	–	−4.39 (−7.21, −1.58) p=0.002
Day 84, n	84	183
LS mean total score (SE)	39.00 (1.268)	34.40 (0.860)
LS mean CFB (SE)	−2.46 (1.268)	−7.05 (0.860)
Treatment difference vs placebo, number (95% CI)  p-value	–	−4.59 (−7.61, −1.57) p=0.003
Day 168, n	78	176
LS mean total score (SE)	37.14 (1.316)	34.12 (0.882)
LS mean CFB (SE)	−4.31 (1.316)	−7.34 (0.882)
Treatment difference vs placebo, number (95% CI)  p-value	–	−3.03 (−6.15, 0.10) p=0.058
CAT Score
Day 28, n	94	199
LS mean score (SE)	14.75 (0.551)	13.26 (0.378)
LS mean CFB (SE)	−0.26 (0.551)	−1.75 (0.378)
Treatment difference vs placebo, number (95% CI)  p-value	–	−1.49 (−2.81, −0.17) p=0.027
Day 84, n	87	189
LS mean score (SE)	14.93 (0.594)	12.83 (0.403)
LS mean CFB (SE)	−0.08 (0.594)	−2.18 (0.403)
Treatment difference vs placebo, number (95% CI)  p-value	–	−2.10 (−3.51, −0.68) p=0.004
Day 168, n	80	179
LS mean (SE)	13.69 (0.648)	13.01 (0.434)
LS mean CFB score (SE)	−1.32 (0.648)	−2.00 (0.434)
Treatment difference vs placebo, number (95% CI)  p-value	-	−0.68 (−2.22, 0.86) p=0.386

Abbreviations: CAT, COPD assessment test, CFB, change from baseline; COPD, chronic obstructive pulmonary disease; CI, confidence interval; LS, least squares; SE, standard error; SGRQ, St George’s Respiratory Questionnaire; UMEC, umeclidinium.

Table 5 Summary of on-Treatment AEs

	Placebo N=101	UMEC N=205
AE, n (%)
On-treatment	56 (55)	122 (60)
Drug-related	7 (7)	13 (6)
Leading to permanent discontinuation of the study medication or withdrawal from the study	6 (6)	11 (5)
Non-fatal SAE, n (%)
On-treatment	9 (9)	15 (7)
Post-treatment	1 (<1)	1 (<1)
On-treatment drug-related	2 (2)	1 (<1)
Fatal SAE, n (%)	0	1 (<1)
Drug-related	0	0
Most Frequent AEs (≥3% of Patients in Either Treatment Arm) n, (%)
Upper respiratory tract infection	13 (13)	25 (12)
Nasopharyngitis	11 (11)	19 (9)
COPD	5 (5)	5 (2)
Urinary tract infection	3 (3)	2 (<1)
Dizziness	2 (2)	6 (3)
Blood glucose increased	3 (3)	2 (<1)
Benign prostatic hyperplasia	3 (3)	0

Abbreviations: AE, adverse event; COPD, chronic obstructive pulmonary disease; SAE, serious AE; UMEC, umeclidinium.