Once-daily fluticasone furoate/vilanterol versus twice-daily fluticasone propionate/salmeterol in patients with asthma well controlled on ICS/LABA

Figures & data

Figure 1. Study disposition. Abbreviations: BID, twice daily; FF, fluticasone furoate; FP, fluticasone propionate; ITT, intent-to-treat; OD, once daily; PP, per protocol; SAL, salmeterol; VI, vilanterol.

Table 1. Patient demographics and baseline characteristics (ITT population).

Characteristic	FF/VI 100/25 OD (N = 504)	FP/SAL 250/50 BID (N = 501)	FP 250 BID (N = 499)	Total (N = 1504)
Age, years
Mean (SD)	44.4 (16.30)	43.0 (15.20)	43.0 (16.58)	43.5 (16.04)
Range	11−78	11−80	12−79	11−80
12−17 years, n (%)	35 (7)	34 (7)	31 (6)	100 (7)
≥15 years, n (%)	485 (96)	488 (96)	481 (95)	1454 (96)
Male, n (%)	190 (38)	165 (33)	185 (37)	540 (36)
Race, n (%)
White	416 (83)	408 (81)	412 (83)	1236 (82)
Black or African American	12 (2)	14 (3)	17 (3)	43 (3)
Asian	10 (2)	11 (2)	5 (1)	26 (2)
Other	66 (13)	68 (14)	65 (13)	199 (13)
Duration of asthma, years
Mean (SD)	14.97 (12.610)	14.60 (12.162)	15.06 (12.134)	14.88 (12.298)
Range	0.3−65.0	0.3−66.0	0.4−65.0	0.3−66.0
Range of duration, n (%)
<1 year	19 (4)	7 (1)	10 (2)	36 (2)
≥1 year to <5 years	97 (19)	103 (21)	84 (17)	284 (19)
≥5 years to <10 years	91 (18)	102 (20)	119 (24)	312 (21)
≥10 years	297 (59)	289 (58)	286 (57)	872 (58)
ACT score
Mean (SD)	23.6 (1.86)	23.5 (2.00)	23.4 (1.98)	—
Range	14−25	10−25	14−25	10−25
At randomization (Visit 3):	n = 495	n = 493	n = 485	n = 1473
Pre-dose FEV1, L
Mean (SD)	2.808 (0.7591)	2.806 (0.7522)	2.867 (0.8096)	2.827 (0.7738)
Range	0.97−5.24	1.07−5.16	1.17−5.73	0.97−5.73
Percent predicted FEV1
Mean (SD)	90.26 (12.544)	89.99 (12.620)	90.47 (12.509)	90.24 (12.551)
Range	40.9−138.7	56.9−129.4	52.4−132.0	40.9−138.7

Abbreviations: ACT, asthma control test; BID, twice daily; FEV₁, forced expiratory volume in 1 second; FF, fluticasone furoate; FP, fluticasone propionate; ITT, intent-to-treat; OD, once daily; SAL, salmeterol; SD, standard deviation; VI, vilanterol.

Table 2. Statistical analysis of change from baseline in evening trough FEV₁ (L) at Week 24^a.

	ITT population (N = 1504)			PP population (N = 1336)
Week 24	FF/VI 100/25 OD (N = 504)	FP/SAL 250/50 BID (N = 501)	FP 250 BID (N = 499)	FF/VI 100/25 OD (N = 445)	FP/SAL 250/50 BID (N = 442)	FP 250 BID (N = 449)
Patients with data for ≥1 visits, n	487	487	479	425	426	419
Patients with data at Week 24, n	454	451	441	353	354	346
LS mean	2.850	2.831	2.726	2.833	2.827	2.713
LS mean change (SE)	0.019 (0.0107)	0.000 (0.0108)	−0.104 (0.0109)	0.020 (0.0120)	0.014 (0.0120)	−0.099 (0.0121)
vs FP/SAL
Difference	0.019			0.006
95% CI	−0.011–0.049			−0.027–0.040
vs FP
Difference	0.123	0.104		0.120	0.113
95% CI	0.093–0.153	0.074–0.134		0.086–0.153	0.080–0.147
p-value	<0.001	<0.001		<0.001	<0.001

^a Repeated measures analysis adjusted for baseline FEV₁, region, sex, age, visit, treatment group and incorporating visit-by-treatment interaction and visit-by-baseline interaction terms.

Abbreviations: BID, twice daily; CI, confidence interval; FEV₁, forced expiratory volume in 1 second; FF, fluticasone furoate; FP, fluticasone propionate; ITT, intent-to-treat; LS, least squares; OD, once daily; PP, per protocol; SAL, salmeterol; SE, standard error; VI, vilanterol.

Figure 2. Change from baseline in evening trough FEV₁ in (a) the ITT population and (b) the PP population (repeated measures analysis). (a) ITT population. (b) PP population. Abbreviations: BID, twice daily; CI, confidence interval; FEV₁, forced expiratory volume in 1 second; FF, fluticasone furoate; FP, fluticasone propionate; ITT, intent-to-treat; LS, least squares; OD, once daily; PP, per protocol; SAL, salmeterol; VI, vilanterol.

Figure 3. Treatment effect for primary/secondary/other efficacy endpoints (ITT analysis). (a) FF/VI 100/25 OD versus FP/SAL 250/50 BID. (b) FF/VI 100/25 OD versus FP 250 BID. (c) FP/SAL 250/50 BID versus FP 250 BID. Abbreviations: ACT, Asthma Control Test; AQLQ (12+), Asthma Quality of Life Questionnaire for 12 years and older; AM, morning; BID, twice daily; CI, confidence interval; FEV₁, forced expiratory volume in 1 second; FF, fluticasone furoate; FP, fluticasone propionate; OD, once daily; PEF, peak expiratory flow; PM, evening; SAL, salmeterol; VI, vilanterol.

Table 3. Summary of AEs, SAEs and AEs of special interest (ITT population; N = 1504).

AEs, n (%)	FF/VI 100/25 OD (N = 504)	FP/SAL 250/50 BID (N = 501)	FP 250 BID (N = 499)
On-treatment AEs^a	229 (45)	213 (43)	221 (44)
Nasopharyngitis	61 (12)	67 (13)	57 (11)
Headache	41 (8)	37 (7)	40 (8)
Pharyngitis	15 (3)	13 (3)	18 (4)
Bronchitis	20 (4)	10 (2)	13 (3)
Influenza	9 (2)	12 (2)	19 (4)
Oropharyngeal pain	13 (3)	12 (2)	8 (2)
On-treatment SAEs^b	6 (1)	4 (<1)	5 (1)
On-treatment/post-treatment AEs of special interest	72 (14)	50 (10)	53 (11)
LRTI excluding pneumonia	22 (4)	13 (3)	18 (4)
Local steroid effects	21 (4)	16 (3)	16 (3)
Hypersensitivity	17 (3)	14 (3)	12 (2)
Cardiovascular effects	7 (1)	9 (2)	6 (1)
Cardiac arrhythmia	4 (<1)	5 (<1)	1 (<1)
Cardiac failure^c	0	1 (<1)	1 (<1)
Hypertension^c	4 (<1)	3 (<1)	4 (<1)
Decreased bone mineral density and associated fractures	3 (<1)	0	1 (<1)
Effects on glucose^c	1 (<1)	2 (<1)	1 (<1)
Ocular effects^c	2 (<1)	0	0
Pneumonia	2 (<1)	0	0
Tremor	1 (<1)	1 (<1)	0

^a On-treatment AEs occurring in ≥3% of patients in any treatment arm are shown.

^b On-treatment SAEs were: abdominal abscess, ankle fracture, cholecystitis acute, epilepsy, foot fracture, hypertension, interventional disc protrusion, invasive lobular breast carcinoma, joint instability, large intestine perforation, osteoarthritis, pneumonia, psychotic disorder, renal colic, synovial cyst and vocal cord leukoplakia (each n = 1).

^c Defined using special MedDRA queries.

Abbreviations: AE, adverse event; BID, twice daily; FF, fluticasone furoate; FP, fluticasone propionate; ITT, intent-to-treat; LRTI, lower respiratory tract infection; MedDRA, Medical Dictionary for Regulatory Activities; OD, once daily; SAE, serious adverse event; SAL, salmeterol; VI, vilanterol.