BackgroundWe evaluated the dose–response of umeclidinium (UMEC; a long-acting muscarinic antagonist) combined with fluticasone furoate (FF; an inhaled corticosteroid [ICS]) in patients with asthma.MethodsIn a double-blind, three-period crossover study, 421 subjects (symptomatic on ICS), were randomized to a sequence of three of seven treatments: FF 100 mcg alone, FF 100 mcg combined with UMEC (15.6, 31.25, 62.5, 125, or 250 mcg), or vilanterol 25 mcg (a long-acting β-agonist), inhaled once-daily for 14 days (12–14-day washout). Trough forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and safety were assessed.ResultsPeriod baseline was a significant covariate, indicating a potential carryover effect between treatment periods. Across all treatment periods, trough FEV1 improved with FF/UMEC 125 and 250 versus FF (treatment difference 0.055 L [both doses]; p = 0.018). FF/UMEC increased morning (15.9–22.9 L/min) and evening (16.2–28.8 L/min) PEF versus FF. As intended assessments were confounded, post hoc Period 1 data analyses were performed, demonstrating significant increases in trough FEV1 with FF/UMEC 31.25, 62.5, and 250 versus FF. Trough FEV1 improvements with FF/UMEC were greater in subjects with fixed (0.095–0.304 L) versus non-fixed (−0.084 to 0.041 L) obstruction. The incidence of on-treatment adverse events was 13–25% across groups. No treatment-related effects on laboratory parameters were reported.ConclusionFF/UMEC may be a viable treatment for patients with asthma symptomatic on ICS; benefit may be most prominent in those with fixed obstruction. The carryover effect suggests future UMEC studies should use an alternative design.ClinicalTrials.gov: NCT01573624.
Background: In patients with uncontrolled asthma despite ICS/LABA, effects of adding LAMA and increasing ICS differ based on treatment outcome and may vary with age. Aim: Analyse effects of adding umeclidinium (UMEC) and increasing fluticasone furoate (FF) on FEV1 and exacerbations by age. Methods: CAPTAIN: Phase IIIA, randomised, double-blind, 24–52-week, parallel-group study in adults with asthma, pre-bronchodilator FEV1 ≥30% and <85% predicted, Asthma Control Questionnaire-6 score ≥1.5. Treatment: once-daily FF/vilanterol (VI) (100/25, 200/25μg) or FF/UMEC/VI (100/31.25/25, 100/62.5/25, 200/31.25/25, 200/62.5/25μg) (Ellipta inhaler). Outcomes: change from baseline in trough FEV1 at Wk 24 and annualised rate of moderate/severe exacerbations for <65- and ≥65-year subgroups (no upper age limit for study entry) for UMEC 62.5μg only. Results: Adding UMEC was associated with a trend towards a greater reduction in exacerbations in the older subgroup vs patients <65 years, whereas increasing FF appeared to have a greater effect in patients <65 years (Figure). Effects of adding UMEC or increasing FF on trough FEV1 were less consistent with age (Figure). Conclusions: Effects of adding UMEC or increasing FF dose on exacerbation rate may vary with age. Method: GSK (205715/NCT02924688).
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
'%3e%3ccircle r='20' fill='%23008'/%3e%3ccircle r='17.5' fill='%23fff'/%3e%3ccircle r='3.5' fill='%23008'/%3e%3cg id='d'%3e%3cg id='c'%3e%3cg id='b'%3e%3cg id='a' fill='%23008'%3e%3ccircle r='.875' transform='rotate(7.5 -8.75 133.5)'/%3e%3cpath d='M0 17.5.6 7 0 2l-.6 5L0 17.5z'/%3e%3c/g%3e%3cuse xlink:href='%23a' transform='rotate(15)'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='rotate(30)'/%3e%3c/g%3e%3cuse xlink:href='%23c' transform='rotate(60)'/%3e%3c/g%3e%3cuse xlink:href='%23d' transform='rotate(120)'/%3e%3cuse xlink:href='%23d' transform='rotate(-120)'/%3e%3c/g%3e%3c/svg%3e)
