Alison Donald

Effects of a combination of umeclidinium/vilanterol on exercise endurance in patients with chronic obstructive pulmonary disease: two randomized, double-blind clinical trials:

Objective: Exercise intolerance is a hallmark of chronic obstructive pulmonary disease (COPD). Methods: Patients with COPD were randomized in two multicentre, double-blind, incomplete block crossover studies. Patients received two of six treatments in sequence (12 weeks each): placebo, umeclidinium (UMEC)/vilanterol (VI) (125/25 mcg or 62.5/25 mcg), VI (25 mcg) or UMEC (62.5 mcg or 125 mcg). Exercise endurance time (EET) and trough forced expiratory volume in 1 second (FEV1) (Week 12) were co-primary endpoints. Safety was monitored throughout. Results: Both studies showed similar 3-hour post-dose EET improvements from baseline for UMEC/VI (Week 12). Significant EET improvements were observed with both UMEC/VI doses versus placebo at Week 12 in Study 418 (UMEC/VI 125/25 mcg: 65.8 s; p = 0.005; UMEC/VI 62.5/25 mcg: 69.4 s; p = 0.003), but not in Study 417, where a placebo effect was evident. Post hoc integrated data analysis showed significant but smaller EET improvements for both UMEC/VI doses versus placebo at Week 12 (UMEC/VI 125/25 mcg: 47.5 s; p = 0.002; UMEC/VI 62.5/25 mcg: 43.7 s; p = 0.001). Both studies showed trough FEV1 improvements at Week 12 for both UMEC/VI doses. The incidence of adverse events was similar between treatment groups within each study. Conclusions: UMEC/VI improved lung function and EET.

Efficacy and safety of once-daily GW870086 a novel selective glucocorticoid in mild-moderate asthmatics: a randomised, two-way crossover, controlled clinical trial.

Abstract Objective: To assess the efficacy of inhaled, repeat doses (28 days) of the glucocorticoid agonist GW870086, which has been designed to inhibit gene transrepression of the glucocorticoid receptor while preserving its transactivation. Methods: This was a randomised, placebo-controlled, two-way crossover study, approved by the independent ethics committees of the study centres. Subjects with FEV1 40–85% of the predicted normal value (n = 36) received GW870086 (1 mg, once-daily) and placebo. Results: No significant change from baseline in forced expiratory volume in one second (FEV1) was seen following administration of GW8780086 1 mg relative to placebo; mean FEV1 (day 28), relative to placebo, was (95% confidence intervals [CI]) −0.077 L (−0.192, 0.038). A moderate positive placebo response was observed on Days 14 and 28: Mean FEV1 (95% CI) was 0.115 L (0.040, 0.189) and 0.115 L (0.019, 0.212), respectively. The placebo response was more notable in treatment period 1 and was larger than the response to GW870086 1 mg on day 28, irrespective of period. Peak expiratory flow rate results were consistent with FEV1 and no difference was seen between the GW870086 and placebo for rescue medication usage. Conclusion: This total lack of effect suggests that repeat-dose GW8700861 mg has suboptimal efficacy in mild to moderate asthma.

A randomized, parallel-group study to evaluate the efficacy of umeclidinium/vilanterol 62.5/25 μg on health-related quality of life in patients with COPD

Background The combination of the inhaled muscarinic antagonist umeclidinium (UMEC) with the long-acting β2-agonist vilanterol (VI) has been shown to provide significant improvements in lung function compared with UMEC, VI, or placebo (PBO) in patients with chronic obstructive pulmonary disease (COPD). This study was specifically designed to support these findings by assessing health-related quality of life and symptomatic outcomes in a similar population. Methods This was a 12-week multicenter, randomized, double-blind, parallel-group, placebo-controlled study. Eligible patients were randomized 1:1 to receive once-daily UMEC/VI 62.5/25 μg (via ELLIPTA® dry powder inhaler) or PBO for 12 weeks. The primary endpoint was St George’s Respiratory Questionnaire (SGRQ) total score at day 84. Secondary efficacy endpoints included rescue albuterol use (puffs/day) over weeks 1–12 and trough forced expiratory volume in 1 second on day 84. Adverse events were also assessed. Results A total of 496 patients were included in the intent-to-treat population in the UMEC/VI (n=248) and PBO (n=248) treatment groups. UMEC/VI 62.5/25 μg provided a significant and clinically meaningful improvement in SGRQ total score at day 84 versus PBO (difference between treatments in SGRQ total score change from baseline: −4.03 [95% confidence interval {CI}: −6.28, −1.79]; P<0.001). UMEC/VI 62.5/25 μg resulted in a statistically significant reduction in rescue albuterol use versus PBO (−0.7 puffs/day [95% CI: −1.1, −0.4]; P<0.001). UMEC/VI 62.5/25 μg provided a significant and clinically meaningful improvement in trough forced expiratory volume in 1 second on day 84 versus PBO (122 mL [95% CI: 71, 172]; P<0.001). The incidence of adverse events was similar between treatments (32% and 30% of patients in the UMEC/VI 62.5/25 μg and PBO groups, respectively). Conclusion The results of this study demonstrate that treatment with UMEC/VI 62.5/25 μg provides clinically important improvements in SGRQ and rescue medication use versus PBO in patients with moderate-to-very-severe COPD.

Correct usage, ease of use, and preference of two dry powder inhalers in patients with COPD: analysis of five phase III, randomized trials

Background Handheld inhalers are used to deliver treatment for COPD. Incorrect usage leads to suboptimal disease control. Complex treatment regimens and use of multiple inhalers may reduce patient compliance. The Anoro Ellipta™ dry powder inhaler (DPI) simultaneously delivers umeclidinium bromide (UMEC) and vilanterol (VI) without coformulation being required. Aim To assess the correct usage and ease of use of the Ellipta™ DPI administering UMEC/VI and to compare patient preference for Ellipta™ with the HandiHaler® through exploratory analyses of patient and observer questionnaires in five Phase III studies. Methods Two Phase III, 3-month double-blind, placebo-controlled studies assessed the correct usage of the Ellipta™ DPI at Day 1 and after 6 weeks, and ease of use of the Ellipta™ DPI using a nonvalidated patient questionnaire after 6 weeks or early withdrawal. In three 6-month, blinded double-dummy, active comparator studies (two Phase IIIa and one Phase IIIb), patients completed a COPD device preference questionnaire between the Ellipta™ DPI and the Handi-Haler® at Day 168 (Week 24) or early withdrawal. Results In the 3-month placebo-controlled studies, ≥98% of patients used the Ellipta™ DPI correctly and 99% of patients found the inhaler easy/very easy-to-use and the dose counter easy/very easy to read. Across the two Phase IIIa active comparator studies, patients consistently stated a preference for the Ellipta™ DPI over HandiHaler® regarding the number of steps to use (59% vs 17%), time taken to use (62% vs 14%), and ease of use (63% vs 15%) regardless of which inhaler contained active drug. Results were consistent in the Phase IIIb active comparator study. Conclusion Delivery of UMEC/VI via the Ellipta™ DPI was considered easy-to-use, and patients with COPD demonstrated clear preference for this inhaler compared with HandiHaler®.

Effects of umeclidinium/vilanterol on exercise endurance in COPD: a randomised study

This multicentre, randomised, double-blind, placebo-controlled, two-period crossover study assessed the effect of umeclidinium/vilanterol (UMEC/VI) on exercise capacity in patients with chronic obstructive pulmonary disease (COPD) using the endurance shuttle walk test (ESWT). Patients were randomised 1:1 to one of two treatment sequences: 1) UMEC/VI 62.5/25 µg followed by placebo or 2) placebo followed by UMEC/VI 62.5/25 µg. Each treatment was taken once daily for 12 weeks. The primary end-point was 3-h post-dose exercise endurance time (EET) at week 12. Secondary end-points included trough forced expiratory volume in 1 s (FEV1) and 3-h post-dose functional residual capacity (FRC), both at week 12. COPD Assessment Test (CAT) score at week 12 was also assessed. UMEC/VI treatment did not result in a statistically significant improvement in EET change from baseline at week 12 versus placebo (p=0.790). However, improvements were observed in trough FEV1 (206 mL, 95% CI 167–246), 3-h post-dose FRC (−346 mL, 95% CI −487 to −204) and CAT score (−1.07 units, 95% CI −2.09 to −0.05) versus placebo at week 12. UMEC/VI did not result in improvements in EET at week 12 versus placebo, despite improvements in measures of lung function, hyperinflation and health status. Umeclidinium/vilanterol: no significant improvements in exercise endurance in COPD versus placebo after 12 weeks http://ow.ly/tc9i30gudVc