Clinical evidence in COPD
Discover the core efficacy and safety data supporting Relvar Ellipta in COPD.
Relvar’s specific combination of components with long-lasting activity delivers 24 hours of continuous efficacy 1–5
24-hour FEV1 of Relvar 92/22mcg (placebo-adjusted curve), days 28–29 (end of study) 5*
- Relvar Ellipta’s 24-hour duration of action means that Relvar only needs to be taken once daily 1
- This was a dose-finding study examining the 24-hour spirometric profile of Relvar Ellipta 92/22 mcg administered once-daily in the morning for 28 days in patients with COPD. The primary endpoint of time-adjusted (weighted mean) 0 to 24-hour FEV1 (AUC) at the end of the 28-day treatment period (period days 28–29) was met (p<0.001) 5
No significant difference in efficacy for once-daily Relvar vs. twice-daily Seretide (fluticasone/salmeterol) 500/50 mcg 6
Mean change from baseline in serial (0–24 hour) wmFEV1 at week 12 6
- Treatment difference 22 mL (95% CI -18 to 63; p=0.282) 6
- Study was powered at 90% to detect a difference of 60 mL (deemed an appropriate difference [from prior studies] for superiority of one treatment over another). In this head-to-head study, the primary superiority endpoint (24-hour FEV1) was not met 6
30% fewer moderate/severe COPD exacerbations with Relvar vs. LABA alone 7
Pooled analysis: Reduction in moderate/severe exacerbation rates vs. LABA alone in patients with exacerbation history 7
- This was a pooled analysis of two 52-week studies in a total of 3,255 patients (N=1,622 and N=1,633, respectively) with at least one COPD exacerbation that required antibiotics and/or systemic/oral corticosteroids or hospitalization in the previous 12 months 7
- The primary endpoint was annual rate of moderate/severe exacerbations 7
*Difference from vilanterol (VI) 22 mcg OD: CI: 0.7 (0.6, 0.8) 7
Relvar delivers a 4.3-unit clinically meaningful improvement in SGRQ (quality of life) vs. baseline 6
Mean change in SGRQ-C score from baseline at 12 weeks 6
- In this head-to-head study of Relvar and Seretide, Relvar exceeded the threshold for a minimal clinically important difference (MCID) in total SGRQ-C score 6 8
- The primary superiority endpoint (change from baseline in 0–24h weighted mean FEV1) was not met. There was no powered comparison between mean SGRQ-C score for the two treatments
At 1 year, significant sustained improvement in lung function vs. LABA alone 7
Pooled analysis: Sustained improvement in trough FEV1 (weeks 2–52) 7
- This was a pooled analysis of two 52-week studies in a total of 3255 patients (N=1622 and N=1633, respectively) with at least one COPD exacerbation that required antibiotics and/or systemic/oral corticosteroids or hospitalization in the previous 12 months. In the pooled analysis, there were significantly fewer moderate/severe exacerbations with Relvar vs. LABA alone (primary endpoint; p<0.001) 7
- Relvar delivered sustained improvement in trough FEV1 from baseline at 52 weeks vs. LABA alone (p<0.001) 7
- There was a 40 mL difference in trough FEV1 with Relvar vs. vilaterol alone at 52 weeks (p<0.001) 7
- Ellipta is designed to improve on the current standard for respiratory inhaler devices, offering highly consistent drug delivery to the lungs of COPD patients across all disease severities (ex vivo data) 9 10†
* Device use assessed in two 12-week crossover exercise studies, with ease of use collected using two patient questionnaires. In two 24-week tiotropium comparator studies, a subject device preference questionnaire was also carried out between Ellipta device and the HandiHaler device with the number of steps, time needed to use and overall preference being captured. 11
** Qualitative interviews conducted in a subset of patients completing 4 phase III clinical trials of Relvar Ellipta 92/22 mcg OD in COPD (N=42) and 2 Phase III clinical trials of Relvar Ellipta 92/22 mcg OD and 184/22 mcg in asthma (N=33). Maintenance inhaler(s) currently or previously used in COPD: HandiHaler/DISKUS/MDI/HFA; in asthma: DISKUS/MDI/HFA. 12
† Study 1: An in vitro performance of both components of Relvar Ellipta was observed to be consistent and reproducible, with little flow dependency, when delivered simultaneously at inhalation parameters that were representative of patients with all severities of asthma and COPD (N=105). All patients could generate a peak inspiratory flow rate (PIFR) greater than 43 L/min. 9 Study 2: Inhalation profiles representative of the full range of inhalation parameters for asthma and COPD patients were replicated using the Electronic Lung. Delivered dose was consistent for both components of Relvar for all patient severities. 10
Relvar is generally well tolerated in patients with COPD and asthma 1
The Phase III safety population for Relvar comprised 6,237 patients with COPD and 7,034 patients with asthma. 1
Safety and tolerability data from the Relvar clinical development programme 1
Note: Most common (≥1/10); common (≥1/100 to <1/10)
- Relvar 92/22 mcg has a safety and tolerability profile in asthma similar to that for Seretide 11314
- In common with other ICS-containing medicines, Relvar Ellipta has the potential to cause systemic side effects, including adrenal suppression, cataracts, glaucoma and growth retardation in children (aged 12 years and older), particularly at high doses prescribed for long periods 1
- In common with other ICS-containing medicines, there is an increased risk of pneumonia in COPD patients treated with Relvar1 (note: Relvar 184/22 mcg is not licensed for COPD)
- Relvar Ellipta SmPC.
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- Slack RJ et al. J Pharmacol Exp Ther 2013; 344:218–230.
- Rossios C et al. Eur J Pharmacol 2011; 670:244–251.
- Boscia JA et al. Clin Ther 2012; 34:1655–1666.
- Agustí A et al. Eur Respir J. 2014;43:763–772.
- Dransfield MT et al. Lancet Respir Med. 2013;1:210–223.
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- Prime D et al. Am J Respir Crit Care Med 2012; 185:A2941.
- Hamilton M et al. Am J Respir Crit Care Med 2012; 185:A2940.
- Riley JH et al. Eur Respir J 2013; 42:P4145.
- Svedsater H et al. BMC Pulm Med 2013; 13:72.
- Seretide Accuhaler SmPC, 2015.
- Woodcock A et al. Chest 2013; 144:1222–1229.
- Kew KM et al. Cochrane Data Syst Rev 2014; 3:CD010115. doi: 10.1002/14651858.CD010115.pub2.