Background The ICS fluticasone propionate (FP) and the LABA formoterol fumarate (FORM) have now been combined in a single aerosol inhaler (FP/FORM; flutiform®). The effect of low- (2 puffs 50/5 µg bid) vs high-dose (2 puffs 250/10 µg bid) FP/FORM on airway responsiveness to AMP was compared in an incomplete block, placebo-controlled, 2-way crossover study. Post hoc data analysis from patients who received both FP/FORM doses is presented.
Methods 62 patients (33M, 29F; =18yrs; reversible FEV1 =60% pred.) discontinued maintenance ICS medication for 2 - 3wks; those showing a provocative dose of AMP producing a 20% decline in FEV1 (AMP PD20 FEV1) of <60 mg were randomised to receive 2 of 3 treatments (FP/FORM high-, low-dose or placebo) during 2 periods of 28 ± 3 days each, separated by 2 - 3wks. AMP challenges were performed pre-dose and repeated 12h after last dose at the end of each treatment period. The difference in changes in AMP PD20 FEV1 (day 1 vs day 28) between treatments were compared by an ANCOVA.
Results 15 patients were randomised to receive both high- and low-dose FP/FORM. The change in AMP PD20 FEV1 was greater with FP/FORM high- compared with low-dose (LS means: high dose = 11 mg; 95% CI 4.3, 27.9; low dose = 4.6 mg, 95% CI 1.8, 11.8), with a statistically significant 2.4 fold difference in AMP PD20 FEV1 (1.2 doubling doses) between doses (LS mean: 2.4; 95% CI 1.3, 4.5; p = 0.012). FP/FORM was well-tolerated; only few (mild or moderate) AEs occurred.
Conclusions A significant dose-response was found between low- and high-dose FP/FORM with the higher dose demonstrating a greater reduction in airway responsiveness to AMP.