Population pharmacokinetic (PK) analysis of fluticasone furoate (FF)/umeclidimium (UMEC)/vilanterol (VI) via a single inhaler in patients with COPD (FULFIL)

Abstract

Background: FULFIL showed statistically significant improvements in trough FEV 1 and health status with once-daily FF/UMEC/VI 100μg/62.5μg/25μg via the ELLIPTA ® inhaler (n=911) vs twice-daily budesonide/formoterol (BUD/FOR) 400μg/12μg via the Turbuhaler ® (n=899) in patients with advanced COPD (Lomas et al. ERJ 2016;48:PA4629). We report the population PK results for FF/UMEC/VI. Methods: PK blood samples (6mL) were taken from 74 patients in the FF/UMEC/VI arm: two samples (sparse; n=64) at weeks 12 (predose; 5–15min post-dose) and 24 (5–15min; 45–90min post-dose); seven samples (serial; n=10) at week 24 (predose; 5–15min, 45–90min, 2.5–4h, 6–8h, 10–12h, 23–24h post-dose). Derived parameters, including area under the curve (AUC) and maximum observed concentration (C max ), for FF (inhaled corticosteroid), UMEC (long-acting muscarinic antagonist) and VI (long-acting β 2 -agonist) from FULFIL were compared with historical data for FF, UMEC and VI mono-/dual therapy. Results: Steady state AUCs (geometric mean, pg*h/mL) from FULFIL were consistent with historical data for FF (188 vs 181 [FF]/182 [FF/VI]), UMEC (341 vs 312) and VI (666 vs 615). Steady state C max (geometric mean, pg/mL) for FF from FULFIL was also consistent with historical data (13.2 vs 11.5 [FF]/11.9 [FF/VI]). C max for UMEC and VI from FULFIL were lower than historical data (UMEC, 55.7 vs 69.3; VI, 101.4 vs 127.9); this was likely due to higher variability associated with smaller sample sizes and is not clinically relevant. Conclusion: Population PK results for FF/UMEC/VI triple therapy were consistent with data for FF, UMEC and VI mono-/dual therapy. Funding GSK (CTT116853)