Spotlight on fluticasone furoate/umeclidinium/vilanterol in COPD: design, development, and potential place in therapy

Figures & data

Table 1 Combination or “closed triple” therapies which are currently in development/available in the world

Drug combination	Manufacturer	Mode of delivery
PT010 (glycopyrronium, formoterol fumarate, and budesonide)	Pearl Therapeutics	Standard MDI
Umeclidinium/fluticasone/vilanterol	GSK/Innoviva Inc.	Ellipta^® dry powder inhaler
Triohale (tiotropium bromide, formoterol fumarate, and ciclesonide), available in India	Cipla	Pressurized MDI (Cipla Rotahaler/Revolizer)

Abbreviation: MDI, metered-dose inhaler.

Table 2 Trials which are currently underway evaluating the safety and efficacy of the triple therapy of UMEC/FF/VI

Study and populations	Design	End points	Results
IMPACT (InforMing the PAthway of COPD Treatment) study (NCT2164513)	Phase III double-blind, three-arm, parallel-group study for closed triple therapy	Co-primary end points: 1) annual rate of moderate and severe exacerbations comparing FF/UMEC/VI with FF/VI; and 2) annual rate of moderate and severe exacerbations comparing FF/UMEC/VI with UMEC/VI	Pending
Target N=10,000 patients across 38 countries	Patients randomized to FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg once daily for 52 weeks	Key secondary end points: 1) changes from baseline in trough FEV1 comparing FF/UMEC/VI and FF/VI; 2) time to first moderate or severe exacerbation in all three arms of the study; and 3) annual rate of severe exacerbations in all three arms of the study
FULFIL (Lung FUnction and quality of LiFe assessment in COPD with closed trIpLe therapy) study (NCT2345161)	Phase III randomized, double-blind, double-dummy, parallel-group multicenter study evaluating once-daily closed triple therapy FF/UMEC/VI (100/62.5/25 µg) inhalation powder versus twice-daily budesonide/formoterol (400/12 µg) via the Turbohaler dry powder inhaler	Co-primary end point: change from baseline in trough FEV1 and SGRQ total score after 24 weeks of treatment	Improvements with FF/UMEC/VI compared to Symbicort^® (budesonide/formoterol 400/12 µg) in: 1) trough
Enrolled 1,810 patients across 162 study sites (911 on FF/UMEC/VI and 899 on budesonide/formoterol)		Secondary end points: 1) effect of FF/UMEC/VI on the annual rate of moderate or severe exacerbations compared with budesonide/formoterol; and 2) safety profile of FF/UMEC/VI compared with budesonide/formoterol over 24 and 52 weeks of treatment	FEV1 (171 mL, 95% CI [148, 194], P<0.001) and 2) SGRQ (−2.2 units, 95% CI [−3.5, −1.0], P<0.001), at 24 weeks
NCT2731846	Phase III, 4 weeks, randomized, double-blind, parallel-group, multicenter study designed to assess the equivalence of closed triple therapy FF/UMEC/VI to open triple therapy (FF/VI + UMEC), with a comparison of both triple therapies to dual therapy (FF/VI) on lung function	Primary end point: change from baseline in trough FEV1 on Day 29	Not yet enrolling
Target N=600		Secondary end points: 1) change from baseline in trough FEV1 on Day 2 and Day 28; 2) change from baseline in trough FEV1 on Days 2, 28, and 29; 3) change from baseline in weighted mean FEV1 0–6 hours on Day 1 and Day 28 (in a subset); and 4) serial FEV1 over 0–6 hours on Day 1 and Day 28 (in a subset)
NCT2729051	Phase IIIB, 24 weeks, randomized, double-blind, parallel-group multicenter study to compare the effect of FF/UMEC/VI with FF/VI + UMEC on lung function after 24 weeks	Primary end point: change from baseline in trough FEV1 at 24 weeks	Currently enrolling
Target N=1,020		Key secondary end points: 1) proportion of responders based on SGRQ total score at Week 24; 2) change from baseline in SGRQ total score at Week 24; 3) proportion of responders based on TDI focal score at Week 24; 4) TDI focal score at Week 24; and 5) time to first moderate or severe exacerbation up to 27 weeks

Note: www.clinicaltrials.gov (accessed October 29, 2016).

Abbreviations: UMEC, umeclidinium; FF, fluticasone furoate; VI, vilanterol; FEV₁, forced expiratory volume in 1 second; SGRQ, St George’s Respiratory Questionnaire; CI, confidence interval; TDI, transitional dyspnea index.