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Clinical Trial
. 2016 Aug 17:11:1921-8.
doi: 10.2147/COPD.S109661. eCollection 2016.

Effects of roflumilast in COPD patients receiving inhaled corticosteroid/long-acting β2-agonist fixed-dose combination: RE(2)SPOND rationale and study design

Stephen I Rennard  1 , Fernando J Martinez  2 , Klaus F Rabe  3 , Sanjay Sethi  4 , Emilio Pizzichini  5 , Andrew McIvor  6 , Shahid Siddiqui  7 , Antonio Anzueto  8 , Haiyuan Zhu  9
Affiliations
Clinical Trial

Effects of roflumilast in COPD patients receiving inhaled corticosteroid/long-acting β2-agonist fixed-dose combination: RE(2)SPOND rationale and study design

Stephen I Rennard et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

Background: Roflumilast, a once-daily, selective phosphodiesterase-4 inhibitor, reduces the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. The RE(2)SPOND study is examining whether roflumilast, when added to an inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fixed-dose combination (FDC), further reduces exacerbations. The methodology is described herein.

Methods: In this Phase IV, multicenter, double-blind, placebo-controlled, parallel-group trial, participants were randomized 1:1 (stratified by long-acting muscarinic antagonist use) to receive roflumilast or placebo, plus ICS/LABA FDC, for 52 weeks. Eligible participants had severe COPD associated with chronic bronchitis, had two or more moderate-severe exacerbations within 12 months, and were receiving ICS/LABA FDC for ≥3 months. The primary efficacy measure is the rate of moderate or severe COPD exacerbations per participant per year. The secondary efficacy outcomes include mean change in prebronchodilator forced expiratory volume in 1 second (FEV1) over 52 weeks, rate of severe exacerbations, and rate of moderate, severe, or antibiotic-treated exacerbations. Additional assessments include spirometry, rescue medication use, the COPD assessment test, daily symptoms using the EXACT-Respiratory symptoms (E-RS) questionnaire, all-cause and COPD-related hospitalizations, and safety and pharmacokinetic measures.

Results: Across 17 countries, 2,354 participants were randomized from September 2011 to October 2014. Enrollment goal was met in October 2014, and study completion occurred in June 2016.

Conclusion: This study will further characterize the effects of roflumilast added to ICS/LABA on exacerbation rates, lung function, and health of severe-very severe COPD participants at risk of further exacerbations. The results will determine the clinical benefits of roflumilast combined with standard-of-care inhaled COPD treatment.

Keywords: ICS/LABA; RE2SPOND; exacerbation; methodology; phosphodiesterase-4; study design.

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Figures

Figure 1
Figure 1
RE2SPOND trial design. Note: aFollow-up was conducted 4 weeks after Visit 8 (last visit) or after early termination visit, as applicable. Abbreviations: ET/LV, early termination or last visit; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; qd, once daily; R, randomization; S, screening; TC, telephone contact.
Figure 2
Figure 2
Timeline of participant enrollments and discontinuations.
See this image and copyright information in PMC

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