Fluticasone/formoterol combination therapy is as effective as fluticasone/salmeterol in the treatment of asthma, but has a more rapid onset of action: an open-label, randomized study

Table 3 Summary of treatment differences in secondary efficacy endpoints

Secondary endpoint	Analysis population	Statistical analysis	Difference Fluticasone/formoterol - fluticasone/salmeterol
Discontinuations due to lack of efficacy (%)	PP	%	–1.1
		95% CI^a,b	–4.6, 2.5*
Time to onset of action of study medication (minutes)	FAS	Hazard ratio	1.64
		95% CI	1.28, 2.10
		p value	< 0.001*
Rescue medication use (% of study days)	FAS	HL estimate	2.24
		95% CI	–0.03, 7.06
		p value	0.157
Rescue medication use (number of uses)	FAS	HL estimate	0.02
		95% CI	0.00, 0.11
		p value	0.164
Pre-dose PEFR at week 12 (L/min)	FAS	LS mean	–13.6
		95% CI	–34.9, 7.6
		p value	0.208
2-hour post-dose PEFR at week 12 (L/min)	FAS	LS mean	–10.0
		95% CI	–33.6, 13.7
		p value	0.408
Other lung function parameters (FVC, MEF₂₅, MEF₅₀ and MEF₇₅)	FAS	LS mean	No statistically significant differences between the treatment groups
		95% CI
		p value
Asthma symptom scores (mean values)	FAS	Mean^c	0.15
		95% CI	–0.04, 0.34
		p value	0.122
Sleep disturbance scores (mean values)	FAS	Mean^c	0.00
		95% CI	–0.12, 0.11
		p value	0.975
Asthma exacerbations: mild/moderate	FAS	n (%)	Fluticasone/formoterol: 11 (10.9)
			Fluticasone/salmeterol: 12 (11.9)
		p value	> 0.999
Asthma exacerbations: severe	FAS	n (%)	Fluticasone/formoterol: 3 (3.0)
			Fluticasone/salmeterol: 1 (1.0)
		p value	0.621
Patient assessment of study medication (scores at week 12)	FAS	Odds ratio	0.495
		95% CI^c	0.289, 0.848
AQLQ (scores at week 12)	FAS	Mean (SD)	Fluticasone/formoterol: 5.4 (1.1)
			Fluticasone/salmeterol: 5.5 (0.9)
		p value	0.051

*Statistically significant non-inferiority (discontinuations due to lack of efficacy) or superiority (time to onset of action) of fluticasone/formoterol versus fluticasone/salmeterol based on sequential gatekeeping approach.
^aNon-inferiority of fluticasone/formoterol to fluticasone/salmeterol is shown if the upper limit of the 95% CI is ≤ 10%.
^b p value not calculated.
^cAdjusted mean from linear model on mean score with treatment group as factor.
AQLQ, Asthma Quality of Life Questionnaire; CI, confidence interval; FAS, full analysis set; FVC, forced vital capacity; HL, Hodges Lehmann; LS, least-squares; MEF₂₅; MEF₅₀; MEF₇₅, maximum expiratory flow rate at, respectively, 25%; 50%; and 75% of the volume to exhale; PEFR, peak expiratory flow rate; PP, per protocol population; SD, standard deviation.