A randomized, blinded study to evaluate the efficacy and safety of umeclidinium 62.5 μg compared with tiotropium 18 μg in patients with COPD

Figures & data

Figure 1 Patient disposition.

Note: *Lack of efficacy includes patients who withdrew due to COPD exacerbation.
Abbreviations: ASE, all subjects enrolled; TIO, tiotropium; UMEC, umeclidinium.

Table 1 Baseline demographics and clinical characteristics (ITT population)

Demographic characteristic	UMEC 62.5 µg (n=509)	TIO 18 µg (n=508)	Total (N=1,017)
Age (years), mean (SD)	64.4 (8.1)	64.1 (8.3)	64.2 (8.2)
Female, n (%)	145 (28)	137 (27)	282 (28)
Current smoker at screening, n (%)	259 (51)	260 (51)	519 (51)
Smoking pack-yearsa	41.2 (21.4)	41.9 (21.9)	41.6 (21.6)
Post-salbutamol FEV1 (L)b, mean (SD)	1.49 (0.41)	1.51 (0.44)	1.50 (0.42)
Post-salbutamol FEV1/FVCb, mean (SD)	48.9 (10.1)	48.2 (10.1)	48.6 (10.1)
Reversibility to salbutamolc,d, mean (SD)
Reversible	161 (32)	153 (30)	314 (31)
Nonreversible	347 (68)	354 (70)	701 (69)
GOLD Grades 1–4 (percent-predicted FEV1), n	508	508	1,016
Grade 2 (moderate COPD), n (%)	281 (55)	283 (56)	564 (56)
Grade 3 (severe COPD), n (%)	227 (45)	225 (44)	452 (44)
GOLD Groups A–D using mMRCb
Group B (low risk, more symptoms), n (%)	244 (48)	229 (45)	473 (47)
Group D (high risk, more symptoms), n (%)	264 (52)	279 (55)	543 (53)
ICS use at screening
ICS users, n (%)	247 (49)	229 (45)	476 (47)
ICS nonusers, n (%)	262 (51)	279 (55)	541 (53)

Notes:

a Smoking pack-years = (number of cigarettes smoked per day/20) × number of years smoked.

b n=508 in UMEC, n=508 in TIO.

c n=508 in UMEC, n=507 in TIO.

d Reversibility was defined as an increase in FEV₁ of ≥12% and ≥200 mL following administration of salbutamol; non-reversibility was defined as an increase in FEV₁ of <200 mL or a ≥200 mL increase that was <12% from pre-salbutamol FEV₁.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global initiative for chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; ITT, intent-to-treat; mMRC, modified Medical Research Council; SD, standard deviation; TIO, tiotropium; UMEC, umeclidinium.

Table 2 Summary of lung function end points (ITT and TFH populations)

End point	UMEC 62.5 µg	TIO 18 µg	Treatment difference versus TIO (95% CI)
Trough FEV1 at day 85a	n=508	n=504
LS mean change from baseline (mL), (SE)	147 (10)	94 (10)	53 (25, 81); P<0.001
Trough FVC at day 85a,b	n=508	n=504
LS mean change from baseline (mL), (SE)	192 (17)	112 (17)	80 (34, 127); P<0.001
0–12 hours post-dose WM FEV1 at day 84c,d	n=148	n=147
LS mean change from baseline (mL), (SE)	152 (22)	113 (23)	39 (−24, 101); P=0.222
12–24 hours post-dose WM FEV1 at day 84c,d	n=148	n=147
LS mean change from baseline (mL), (SE)	55 (20)	−15 (20)	70 (14, 127); P=0.015
0–24 hours post-dose WM FEV1 at day 84c,d	n=148	n=147
LS mean change from baseline (mL), (SE)	104 (21)	49 (21)	55 (−2, 113); P=0.058

Notes:

a ITT population.

b Analysis was performed using a repeated measures model with covariates of treatment, baseline FVC, center group, 24-hour subset flag, day, day-by-baseline, and day-by-treatment interactions.

c TFH population.

d Analysis performed using a repeated measures model with covariates of treatment, baseline FEV₁, center group, day, day-by-baseline and day-by-treatment interactions.

Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; ITT, intent-to-treat; LS, least squares; SE, standard error; TFH, 24-hour; TIO, tiotropium; UMEC, umeclidinium; WM, weighted mean.

Figure 2 LS mean change from baseline in trough FEV₁ (mL) (PP population).

Notes: n₁, number of patients with analyzable data for ≥1 time points. n₂, number of subjects with analyzable data at the current time point.
Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 second; LS, least squares; PP, per-protocol; SE, standard error; TIO, tiotropium; UMEC, umeclidinium.

Figure 3 LS mean change from baseline in serial FEV₁ (mL) on day 1 (A) and on day 84 (B) (both days: TFH population).

Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 second; LS, least squares; TFH, 24-hour; TIO, tiotropium; UMEC, umeclidinium.

Table 3 Summary of symptomatic and health-related quality of life end points (ITT population)

End point	UMEC 62.5 µg	TIO 18 µg	Treatment difference versus TIO (95% CI)
TDI focal score at day 84	n=492	n=490
LS mean (SE)	1.96 (0.13)	1.90 (0.13)	0.06 (−0.30, 0.42); P=0.746
TDI responder at day 84, n (%)a	277 (55)	279 (55)	0.97 (0.76, 1.25);b P=0.816
SGRQ score at day 84	n=481	n=486
LS mean change from baseline (SE)	−6.03 (0.57)	−5.57 (0.57)	−0.46 (−2.04, 1.13); P=0.571
SGRQ responder at day 84, n (%)c	241 (48)	237 (47)	1.05 (0.81, 1.35);b P=0.727
CAT score, day 84	n=493	n=492
LS mean change from baseline (SE)	−1.83 (0.25)	−1.62 (0.25)	−0.21 (−0.91, 0.48); P=0.547
CAT responder at day 84, n (%)d	253 (50)	228 (45)	1.24 (0.96, 1.60);b P=0.104
Rescue use (mean puffs/day) weeks 1–12	n=480	n=484
LS mean change from baseline, (SE)	−0.9 (0.1)	−0.8 (0.1)	0.0 (−0.2, 0.1); P=0.557
Rescue use (% rescue-free days)e	n=480	n=484
Estimated median difference (95% CI)			0 (0.00, 0.18); P=0.484

Notes:

a TDI responders were defined as patients with a ≥1 unit TDI focal score.

b Odds ratio.

c Response was defined as a reduction from baseline of ≥4 units in SGRQ score.

d Response was defined as a reduction from baseline of ≥2 units in CAT score.

e Hodges–Lehmann estimates for the median treatment difference and 95% CI are based upon a Wilcoxon rank-sum test; P-value is based on van Elteren test.

Abbreviations: CAT, COPD Assessment Test; CI, confidence interval; ITT, intent-to-treat; LS, least squares; SE, standard error; SGRQ, St George’s Respiratory Questionnaire; TDI, transition dyspnea; TIO, tiotropium; UMEC, umeclidinium.

Table 4 Inhaler assessments

Assessment type	UMEC 62.5 µg (n=509)	TIO 18 µg (n=508)	Total (N=1,017)
Overall device preference at the end of the treatment phase,a n (%)
ELLIPTA™	280 (56)	290 (59)	570 (57)
HandiHaler^®	111 (22)	78 (16)	189 (19)
No preference	107 (21)	126 (26)	223 (23)
Inhaler ease of use at day 84,b n (%)
ELLIPTA™
Very easy	294 (62)	296 (62)	590 (62)
Easy	154 (33)	158 (33)	312 (33)
Neutral	22 (5)	21 (4)	43 (5)
Difficult	1 (<1)	2 (<1)	3 (<1)
Very difficult	0	0	0
HandiHaler^®
Very easy	164 (35)	178 (37)	342 (36)
Easy	196 (42)	198 (42)	394 (42)
Neutral	79 (17)	74 (16)	153 (16)
Difficult	29 (6)	27 (6)	56 (6)
Very difficult	3 (<1)	0	3 (<1)

Notes:

a Number of patients with analyzable data: UMEC =498, TIO =494, and total =992.

b Number of patients with analyzable data: UMEC =471, TIO =477, and total =948.

Abbreviations: TIO, tiotropium; UMEC, umeclidinium.

Figure 4 Proportion of trough FEV₁ responders.

Notes: *P<0.05. Response was defined as an increase of ≥100 mL above baseline FEV₁.
Abbreviations: CI, confidence interval; OR, odds ratio; FEV₁, forced expiratory volume in 1 second; TIO, tiotropium; UMEC, umeclidinium.

Table 5 Summary of safety results (ITT population)

Safety measure	UMEC 62.5 µg (n=509)	TIO 18 µg (n=508)
Any on-treatment AE, n (%)	165 (32)	153 (30)
Most common on-treatment AEs reported by ≥3% of patients in either treatment group, n (%)
Headache	30 (6)	32 (6)
Nasopharyngitis	27 (5)	23 (5)
Any on-treatment nonfatal SAEs, n (%)	17 (3)	14 (3)
Any on-treatment fatal SAEs, n (%)	0	2 (<1)
Any on-treatment drug-related AEs, n (%)	17 (3)	8 (2)
Number of patients with a COPD exacerbation, n (%)	58 (11)	48 (9)

Abbreviations: AE, adverse event; ITT, intent-to-treat; SAEs, serious adverse events; TIO, tiotropium; UMEC, umeclidinium.