A randomized, parallel-group study to evaluate the efficacy of umeclidinium/vilanterol 62.5/25 μg on health-related quality of life in patients with COPD

Figures & data

Table 1 Summary of patient demographics and baseline characteristics (ITT population)

	UMEC/VI 62.5/25 μg (n=248)	PBO (n=248)
Age, years	64.1 (8.70)	62.6 (8.23)
Male, n (%)	144 (58)	149 (60)
Current smoker at screening,a n (%)	137 (55)	129 (52)
Smoking pack-yearsb	38.82 (20.44)	38.40 (22.55)
ICS use at screening,c n (%)	111 (45)	124 (50)
Post-albuterol % predicted FEV1	46.5 (12.81)	48.4 (14.06)
Post-albuterol FEV1/FVC	47.81 (10.93)	49.75 (11.23)
Reversible to albuterol,d,e n (%)	55 (22)	54 (22)
Reversibility to albuterol,e %	11.5 (15.28)	10.8 (13.49)
% Rescue-free days,f mean (SD)	20.4 (34.54)	23.5 (35.94)
Rescue albuterol use, puffs/day,f mean (SD)	3.8 (3.32)	3.4 (3.57)
SGRQ score at baseline,g mean (SD)	48.14 (17.08)	47.58 (17.25)
GOLD category, n (%)
GOLD B	90 (36)	109 (44)
GOLD D	158 (64)	139 (56)

Notes: Values are reported as mean (SD) unless otherwise stated.

a Reclassified: subject reclassified as current smoker if smoked within 6 months.

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

c ICS use was defined as those patients who were currently taking ICS-containing medications at the screening visit.

d Reversibility was defined as an increase in FEV₁ of ≥12% and ≥200 mL following administration of albuterol.

e UMEC/VI 62.5/25 μg, n=247; PBO, n=247.

f UMEC/VI 62.5/25 μg, n=244; PBO, n=247.

g UMEC/VI 62.5/25 μg, n=239; PBO, n=236.

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; PBO, placebo; SD, standard deviation; SGRQ, St George’s Respiratory Questionnaire; UMEC, umeclidinium; VI, vilanterol.

Figure 1 Summary of patient disposition.

Notes: *Two patients were randomized in error and are included in the pre-screen and screening failures. Patients in the intent-to-treat population were enrolled from the following countries; US (n=125), Ukraine (n=56), Russian Federation (n=78), Romania (n=56), Hungary (n=76), Germany (n=52), and Bulgaria (n=53).
Abbreviations: PBO, placebo; UMEC, umeclidinium; VI, vilanterol.

Table 2 Summary of SGRQ endpoints (ITT population)

	UMEC/VI 62.5/25 μg (n=248)	PBO (n=248)
SGRQ score on day 28
LS mean change from baseline (SE)a	−5.41 (0.711)	−0.14 (0.717)
Difference vs PBO (95% CI)	−5.27 (−7.26, −3.28)*
Proportion of respondersb,c according to SGRQ total score on day 28
Responder, n (%)	113 (48)	67 (29)
OR vs PBO, (95% CI)	2.35 (1.58, 3.49)*
SGRQ score on day 56
LS mean change from baseline (SE)d,e	−6.04 (0.775)	−2.30 (0.778)
Difference vs PBO (95% CI)	−3.73 (−5.89, −1.57)*
Proportion of respondersb,f according to SGRQ total score on day 56
Responder, n (%)	119 (51)	94 (40)
OR vs PBO, (95% CI)	1.53 (1.05, 2.23)**
SGRQ score on day 84
LS mean change from baseline (SE)g	−6.15 (0.803)	−2.12 (0.808)
Difference vs PBO (95% CI)	−4.03 (−6.28, −1.79)*
Proportion of respondersb,h according to SGRQ total score on day 84
Responder, n (%)	123 (51)	94 (40)
OR vs PBO, (95% CI)	1.61 (1.11, 2.34)***

Notes:

* P<0.001;

** P=0.026;

*** P=0.013.

a Number of patients with analyzable data at this time point: UMEC/VI 62.5/25 μg, n=225; PBO, n=221.

b Response is defined as an SGRQ total score of 4 units below baseline (scores recorded prior to dosing on day 1 or lower).

c UMEC/VI 62.5/25 μg, n=236; PBO, n=232.

d Number of patients with analyzable data at this time point: UMEC/VI 62.5/25, n=220; PBO, n=220.

e LS mean change from baseline: UMEC/VI 62.5/25 μg, −6.0381; PBO, −2.3047.

f UMEC/VI 62.5/25 μg, n=235; PBO, n=235.

g Number of patients with analyzable data at this time point: UMEC/VI 62.5/25 μg, n=212; PBO, n=210.

h UMEC/VI 62.5/25 μg, n=239; PBO, n=236.

Abbreviations: CI, confidence interval; ITT, intent-to-treat; LS, least squares; OR, odds ratio; PBO, placebo; SE, standard error; SGRQ, St George’s Respiratory Questionnaire; UMEC, umeclidinium; VI, vilanterol.

Figure 2 LS mean (95% CI) change from baseline in SGRQ total over time (ITT population).

Note: ***P<0.001.
Abbreviations: CI, confidence interval; ITT, intent-to-treat; LS, least squares; MCID, minimum clinically important difference; PBO, placebo; SGRQ, St George’s Respiratory Questionnaire; UMEC, umeclidinium; VI, vilanterol.

Figure 3 LS mean (95% CI) change from baseline in trough FEV₁ (mL) over time (ITT population).

Note: ***P<0.001.

Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 second; ITT, intent-to-treat; LS, least squares; PBO, placebo; UMEC, umeclidinium; VI, vilanterol.

Figure 4 LS mean change from baseline in trough FVC (mL) over time (ITT population).

Note: ***P<0.001.
Abbreviations: FVC, forced vital capacity; ITT, intent-to-treat; LS, least squares; PBO, placebo; UMEC, umeclidinium; VI, vilanterol.

Table 3 Summary of AEs (ITT population)

	UMEC/VI 62.5/25 μg (n=248)	PBO (n=248)
On-treatment AEs, n (%)	80 (32)	75 (30)
Any AEs leading to withdrawal/discontinuation of medication,a n (%)	8 (3)	6 (2)
On-treatment nonfatal SAE, n (%)	17 (7)	13 (5)
On-treatment fatal SAE, n (%)	2 (<1)	0
AEs reported in ≥3% patients, n (%)
Headache	16 (6)	16 (6)
Nasopharyngitis	13 (5)	16 (6)
COPDb	8 (3)	7 (3)
Patients experiencing a COPD exacerbation,c n (%)	18 (7)	28 (11)
Total no of exacerbations	21	32
Withdrawn due to an exacerbationd	4 (19)	7 (22)
Requiring oral/systemic corticosteroidd	12 (57)	16 (50)
Requiring antibioticsd	16 (76)	27 (84)
Requiring emergency room visitd	3 (14)	2 (6)
Requiring hospitalizationd	12 (57)	11 (34)

Notes:

a Includes both on- and posttreatment AEs.

b COPD was listed as an AE by the participating investigator and was likely due to a worsening of the underlying condition, although no further information is available in the AE reporting.

c COPD exacerbations were not to be recorded as AEs unless they met the definition of an SAE.

d Proportion of the number of exacerbations per treatment group.

Abbreviations: AE, adverse event; COPD, chronic obstructive pulmonary disease; ITT, intent-to-treat; PBO, placebo; SAE, serious adverse event; UMEC, umeclidinium; VI, vilanterol.

Table S1 Excluded medications prior to visit 1

Medication
Depot corticosteroids
Systemic, oral or parenteral corticosteroidsa
ICS/LABA combination products
Use of ICS at a dose >1,000 μg/day of fluticasone propionate or equivalent
Initiation or discontinuation of ICS use
Phosphodiesterase 4 inhibitors (roflumilast)
LAMAs (tiotropium, aclidinium, glycopyrronium, umeclidinium)
Inhaled LABAs (salmeterol, formoterol, indacaterol, vilanterol)
LAMA/LABA combination products
Theophyllines
Oral β2 -agonists
Inhaled short-acting β2 -agonistsb
Inhaled short-acting anticholinergics
Inhaled short-acting anticholinergic/short-acting β2 -agonist combination products
Any other investigational medication

Notes:

a Except for the treatment of COPD exacerbations during the study, which did not exceed 14 days. Localized corticosteroid injections were permitted.

b Use of study-provided albuterol was permitted during the study, except in the 4-hour period prior to spirometry testing.

Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist.