Dose responses for topical efficacy and systemic activity, dose equivalence and relative therapeutic index for fluticasone furoate (FF), fluticasone propionate (FP) and budesonide (BUD) in asthmatic subjects

This abstract will be presented at ERS 2019 in Madrid, Spain.

Maximilian Stadler is presenting this Encore on behalf of all authors with their permissions.

FF is an inhaled corticosteroid (ICS) with higher glucocorticoid receptor affinity, tissue permeability and lung retention than other ICS. We investigated whether these attributes improve the therapeutic index (TI), defined as topical efficacy to systemic activity ratio.

In this escalating dose, randomised, incomplete-block, 2-period cross-over study (GSK study 203 162, NCT02991859), 54 asthmatic subjects were randomised to one or two of four treatment periods. Each period comprised five dose escalations (µg/d) of 7-days duration: FF (25,100, 200, 400, 800), FP (50, 200, 500,1000, 2000), BUD (100, 400, 800,1600, 3200) or placebo, with a ≥ 25-day washout between periods. At the end of each escalation, 12 h adenosine-5'-monophosphate (AMP) challenge PC₂₀ and 24 h plasma cortisol were assessed. Both endpoints showed a dose response ([Fig. 1]).

Fig. 1 Dose responses for AMP PC₂₀ (mg/mL) and 24 h plasma cortisol suppression (%) (predicted values, 95% CI).

The ED₅₀ µg/d (95% CI) values were: 49 (18,129), 1081 (448,2610), and 1467 (547,3940) for AMP PC₂₀ and 900 (698,1102), 1986 (1575,2397) and 1927 (1699,2156) for 24 h plasma cortisol and TI values (ED₅₀ 24 h cortisol/ED₅₀ AMP PC₂₀) were 18.6, 1.84 and 1.31 for FF, FP and BUD respectively. No on treatment SAEs were reported.

Within the approved dose ranges for asthma, FF gave more protection against airway hyperresponsiveness with less systemic activity compared to FP or BUD.

Funding: GSK [203162, NCT02991859]