POSTER NO. 806 Once-daily (OD) fluticasone furoate/vilanterol 100/25mcg (FF/VI) compared with twice-daily (BD) fluticasone propionate/salmeterol 250/50mcg (FSC) in patients with COPD Dransfield M(1), Crim C(2), Feldman G

Once-daily (OD) fluticasone furoate/vilanterol 100/25mcg (FF/VI) compared with twice-daily (BD) fluticasone propionate/salmeterol 250/50mcg (FSC) in patients with COPD

Dransfield M(1), Crim C(2), Feldman G(3), Korenblat P(4), LaForce C(5), Locantore N(2), Pistolesi M(6), Watkins M(2), Martinez F(7)

(1)University of Alabama, Birmingham, AL, USA; (2)GlaxoSmithKline, Research Triangle Park, NC, USA; (3)S. Carolina Pharmaceutical Research, SC, USA; (4)The Clinical Research Center, St Louis, MO, USA; (5)North Carolina Clinical Research, Raleigh, NC, USA; (6)University of Florence, Florence, Italy; (7)University of Michigan, Ann Arbor, MI, USA

Currently available ICS/LABA combinations for moderate/severe COPD require twice-daily dosing.

FF and VI are, respectively, a novel ICS and LABA in development as a once-daily combination therapy (FF/VI) for COPD and asthma.

To compare the efficacy and safety profiles of once-daily FF/VI 100/25mcg with twice-daily FSC (250/50mcg) in patients with moderate/severe COPD.

Two randomized, double-blind, double-dummy, multi-center parallel-group studies (HZC109 [Study 1] and HZC352 [Study 2]), of 12 weeks duration, were identical in design, conduct and analysis.

Patients (>40 years of age, >10 pack-years smoking history, post-bronchodilator FEV1 <70%, FEV1/FVC ratio <0.70 at screening, no requirement of prior exacerbations) completed a 2-week placebo run-in and were randomized 1:1 to once-daily (morning) FF/VI 100/25 via the ELLIPTA two-strip dry powder inhaler, or twice-daily FSC 250/50 via DISKUS .

Primary endpoint was change from baseline in weighted mean (wm) 0 24h FEV1 on Day 84. Secondary endpoint was time to onset on Day 1. Safety was assessed throughout the study.

Outcomes of the individual studies and pooled data are presented. A step-down statistical hierarchy was applied to analysis of the individual studies but not the pooled data. In Study 1 and Study 2, a statistically significant (p<0.05) treatment difference on the primary endpoint was required for statistical inference to be drawn on subsequent endpoints.

1030 patients (Study 1: 519; Study 2: 511) were randomized and received at least one dose of study medication (intent-to-treat [ITT] population). 950 completed the studies. On-treatment withdrawal rates were 8% in both treatment arms.

Patient demographics were well matched (Table 1).

Table 1. Patient demographics and screening characteristics

(pooled data, ITT population)

Values are mean (SD) unless otherwise stated

Efficacy: primary endpoint

Change from baseline in 0 24h wmFEV1 on Day 84 was significantly (p<0.001) greater with FF/VI than with FSC in Study 1 and in the pooled analysis, but not in Study 2 (Table 2).

An overall pattern of greater lung function over 24h on Day 84 was observed with FF/VI compared with FSC (Figure 1).

Table 2. Change from baseline 0 24h wmFEV1 (mL) after 12 weeks

(Study 1, Study 2 & pooled, ITT population)

Values are least squares mean (SD) unless otherwise stated

Figure 1. LS mean FEV1 change from baseline over 24h, Day 84

(pooled data, ITT population)

CI=confidence interval; LS=least squares

Efficacy: secondary endpoint

Median time to >100mL increase from baseline FEV1 was significantly faster with FF/VI (15 16min) than FSC (30min) in Study 1 (p=0.012) and in the pooled analysis (p=0.026) (Figure 2), but significance could not be inferred for Study 2 (FF/VI: 16min, FSC: 30min).

Figure 2. Cumulative % of patients achieving >100mL increase

from baseline FEV1, Day 1 (pooled data, ITT population)

Table 3. Summary of on-treatment AEs by treatment group

(pooled data, ITT population)

AEs occurring in >3% of patients in either treatment group shown

AE=adverse event, SAE=serious adverse event

AE frequency was similar between treatment groups (Table 3).

No abnormalities of clinical concern were observed in either study for laboratory values, including urinary cortisol, or ECG readings.

A statistically significant treatment difference (FF/VI - FSC) in 0 4h weighted mean pulse rate (95% CI) of 1.9bpm ( 3.3, 0.5) was observed at Week 12 in Study 1; this difference was not considered to be clinically significant. No difference in weighted mean pulse rate was observed between FF/VI and FSC in Study 2.

Pooled analysis of these two replicate studies found once-daily FF/VI 100/25 to produce a greater improvement in 24h lung function than twice-daily FSC 250/50 after 12 weeks of treatment.

FF/VI confers a more rapid improvement in lung function than FSC in the first hour of dosing on Day 1.

No baseline factors that may explain the differential outcomes of Study 1 and Study 2 were apparent.

No substantial safety concerns were identified in relation to FF/VI. Both treatments were well tolerated overall with similar safety profiles.

The presenting author, Mark Dransfield, declares the following real or perceived conflicts of interest during the last 3 years in relation to this presentation: has served as a consultant for Boehringer Ingelheim (BI), GlaxoSmithKline (GSK) and Ikaria. He has received grant funding from the NHLBI for COPD-related research and contracted research funding from Aeris, AstraZeneca, BI, Boston Scientific, Centocor, Forrest, GSK, Ikaria, MedImmune, Otsuka and Pfizer.

This research was funded by GlaxoSmithKline. GSK study codes (clinicaltrials.gov): HZC113109 (NCT01323634); HZC112352 (NCT01323621).

Editorial support (in the form of writing assistance, assembling tables and figures, collating author comments, grammatical editing and referencing) was provided by Ian Grieve, PhD at Gardiner-Caldwell Communications (Macclesfield, UK) and was funded by GlaxoSmithKline.

ELLIPTA is a trade mark of GlaxoSmithKline

Presented at the American Thoracic Society Annual Congress, Philadelphia, PA, USA, 17 22 May 2013