Fluticasone propionate/formoterol for COPD management: a randomized controlled trial

Figures & data

Table 1 Patient demographic and baseline COPD characteristics (full analysis population)

	FP/FORM 500/20 µg	FP/FORM 250/10 µg	FORM 12 µg
Age (years), mean (SD)	63.8 (7.92)	63.0 (7.81)	64.0 (7.87)
Gender (%)
Male/female	75.5/24.5	72.6/27.4	75.9/24.1
Race
Caucasian (%)	98.1	95.9	97.1
Other (%)	1.9	4.1	2.9
Duration COPD (years), mean (SD)	8.1 (6.05)	7.8 (5.86)	8.65 (6.91)
Smoking status, current/ex (%)	45.7/54.3	49.1/50.9	50.0/50.0
Smoking exposure (pack-years), mean (SD)	39.1 (19.5)	39.2 (20.1)	40.2 (21.0)
Pre-bronchodilator FEV1 % predicted, mean (SD)	35.6 (8.51)	35.9 (8.31)	35.7 (8.81)
Post-bronchodilator FEV1 % predicted, mean (SD)	37.8 (7.88)	38.0 (7.74)	37.7 (7.95)
FEV1 reversibility (%), mean (SD)	7.7 (12.13)	7.4 (12.76)	7.4 (13.46)
Post-bronchodilator FEV1/FVC ratio (%), mean (SD)	41.4 (9.69)	42.3 (10.07)	42.1 (9.69)
Moderate or severe exacerbation frequency in past year, by category (%)
<2 events	71.0	70.4	70.7
≥2 events	29.0	29.6	29.3
Time since last exacerbation (days), mean (SD)	131.8 (93.07)	136 (95.50)	143.3 (98.33)
SGRQ-C score (units), mean (SD)	53.9 (17.94)	53.5 (17.30)	54.8 (17.63)
Rescue use (occasions/day), mean (SD)	2.3 (1.77)	2.3 (1.79)	2.3 (1.81)
COPD medication, (%)
ICS	14.1	14.6	14.2
LABA	21.6	18.4	25.3
ICS/LABA	59.5	62.4	58.3
LAMA	60.0	60.2	59.7
PDE4 inhibitors	0.7	1.7	1.5
Xanthines	27.4	31.5	32.7

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 s; FP, fluticasone propionate; FORM, formoterol fumarate; FVC, forced vital capacity; SGRQ-C, St George’s Respiratory Questionnaire for COPD; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; PDE4, inhibitor, phosphodiesterase type 4 inhibitor.

Figure 1 Patient disposition.

Abbreviations: TIO, tiotropium bromide; FP, fluticasone propionate; FORM, formoterol fumarate.

Figure 2 Time to discontinuation.

Abbreviations: FP, fluticasone propionate; FORM, formoterol fumarate.

Table 2 Moderate/severe exacerbations analysis (full analysis population)

	FP/FORM 500/20 µg	FP/FORM 250/10 µg	FORM 12 µg
Number of moderate/severe exacerbation events (%)
0	56.7	59.9	60.0
1	28.1	25.0	22.7
2	10.4	9.0	10.5
≥3	4.8	6.1	6.8
Rate moderate/severe exacerbations (events/patient/year)	0.81	0.81	0.87
Rate ratio (95% CIs) versus FORM	0.93 (0.79, 1.10) P=0.401	0.93 (0.79, 1.10) P=0.402
Time to first moderate/severe exacerbation
Hazard ratio versus FORM	1.02 (0.86, 1.23) P=0.801	0.96 (0.80, 1.16) P=0.635

Abbreviations: FP, fluticasone propionate; FORM, formoterol fumarate.

Table 3 Average pre- and post-dose FEV₁ and FVC over the study (full analysis population)

	FP/FORM 500/20 µg	FP/FORM 250/10 µg	FORM 12 µg
Pre-dose FEV1 (L; LS mean)	1.03	1.02	1.00
Difference (95% CIs) versus FORM	0.029 (0.009, 0.049) P=0.004	0.020 (0.000, 0.040) P=0.049
1-hour post-dose FEV1 (L; LS mean)	1.13	1.12	1.09
Difference (95% CIs) versus FORM	0.038 (0.017, 0.059) P<0.001	0.029 (0.008, 0.050) P=0.007
Pre-dose FVC (L; LS mean)	2.50	2.48	2.46
Difference (95% CIs) versus FORM	0.040 (0.002, 0.079) P=0.039	0.025 (−0.014, 0.063) P=0.209
1-hour post-dose FVC (L; LS mean)	2.70	2.68	2.64
Difference (95% CIs) versus FORM	0.064 (0.025, 0.104) P=0.001	0.043 (0.004, 0.083) P=0.031

Abbreviations: FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; FP, fluticasone propionate; FORM, formoterol fumarate; L, liters; LS mean, least squares mean.

Table 4 EXACT exacerbations analysis (full analysis population)

	FP/FORM 500/20 µg	FP/FORM 250/10 µg	FORM 12 µg
Number of moderate/severe exacerbation events (%)
0	48.4	47.1	48.5
1	28.3	27.6	27.8
2	12.6	12.4	11.7
≥3	10.7	12.9	12.0
Rate moderate/severe exacerbations (events/patient/year)	1.02	1.16	1.17
Rate ratio (95% CIs) versus FORM	0.87 (0.75, 1.01) P=0.077	0.99 (0.85, 1.14) P=0.853

Abbreviations: EXACT, EXAcerbations of Chronic pulmonary disease Tool; FP, fluticasone propionate; FORM, formoterol fumarate.

Figure 3 Change from baseline SGRQ-C.

Abbreviations: SGRQ-C, St George’s Respiratory Questionnaire for COPD; FP, fluticasone propionate; FORM, formoterol fumarate.

Figure 4 Time to clinically important deterioration.

Abbreviations: FP, fluticasone propionate; FORM, formoterol fumarate.

Table 5 Overall incidence of adverse events (safety population)

	FP/FORM 500/20 µg	FP/FORM 250/10 µg	FORM 12 µg
Subjects with ≥1 adverse event (%)	42.2	44.2	40.7
Subjects with ≥1 severe adverse event (%)	9.7	9.0	8.1
Subjects with ≥1 serious* adverse event (%)	10.7	12.8	9.8
Subjects with ≥1 adverse event leading to discontinuation (%)	4.1	5.8	4.4

Note:

* Serious adverse events defined as fatal, life-threatening, (prologation of existing) hospitalization, persistent/significant incapacity, requires intervention to prevent permanent impairment.

Abbreviations: FP, fluticasone propionate; FORM, formoterol fumarate.

Table 6 Incidence (%) of frequent adverse events by system organ class (safety population)

	FP/FORM 500/20 µg	FP/FORM 250/10 µg	FORM 12 µg
Infections and infestations	15.7	19.9	18.0
Cardiac disorders	10.4	9.7	9.7
Respiratory, thoracic and mediastinal disorders	8.2	7.8	5.8
Investigations	3.7	6.5	5.4
Gastrointestinal disorders	6.1	4.6	4.1
Metabolism and nutrition disorders	4.6	3.9	5.8
Vascular disorders	4.9	4.9	3.7
Musculoskeletal and connective tissue disorders	4.9	4.3	3.9
Nervous system disorders	2.9	3.7	2.9

Abbreviations: FP, fluticasone propionate; FORM, formoterol fumarate.