Effect of background long-acting beta2-agonist therapy on the efficacy and safety of a novel, nebulized glycopyrrolate in subjects with moderate-to-very-severe COPD
Received 26 April 2018
Accepted for publication 30 July 2018
Published 19 September 2018 Volume 2018:13 Pages 2917—2929
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Dr Richard Russell
Edward M Kerwin,1 Robert Tosiello,2 Barry Price,2 Shahin Sanjar,2 Thomas Goodin2
1Clinical Research Institute of Southern Oregon, Inc., Medford, OR, USA; 2Sunovion Pharmaceuticals Inc., Marlborough, MA, USA
Background: Phase III studies demonstrated efficacy and safety of nebulized glycopyrrolate inhalation solution (GLY) in subjects with COPD. Secondary analyses were performed to examine the effect of background long-acting beta2-agonist (LABA) use on the efficacy and safety of nebulized GLY.
Methods: In two 12-week placebo-controlled studies (GOLDEN 3 and GOLDEN 4) and one 48-week, open-label active-controlled study (GOLDEN 5), a total of 2,379 subjects were stratified by background LABA use (LABA-yes: n=861; LABA-no: n=1,518) and randomized to placebo vs GLY 25 or 50 µg twice daily, or GLY 50 µg twice daily vs tiotropium (TIO) 18 µg once daily. Lung function, patient-reported outcomes, exacerbations, and safety were assessed.
Results: Compared with placebo, pooled data from the 12-week studies showed significant improvements from baseline with GLY 25 and 50 µg across LABA subgroups in trough FEV1 (LABA-yes: 0.101 and 0.110 L; LABA-no: 0.092 and 0.101 L, respectively; P<0.001) and St George’s Respiratory Questionnaire total score (SGRQ; LABA-yes: -2.957 and -3.888; LABA-no: -3.301 and -2.073, respectively; P<0.05). Incidence of treatment-emergent adverse events (TEAEs) was similar in LABA subgroups, and lower in GLY 25 µg vs placebo. In the 48-week active-controlled study, GLY and TIO both showed improvement from baseline across LABA subgroups in FEV1 (LABA-yes: 0.106 and 0.092 L; LABA-no: 0.096 and 0.096 L, respectively) and in SGRQ total score (LABA-yes: -5.190 and -3.094; LABA-no: -4.368 and -4.821, respectively). Incidence of TEAEs was similar between GLY and TIO, and across LABA subgroups. Exacerbation rates were similar across treatments and LABA subgroups, and cardiovascular events of special interest were more frequent in the LABA-no subgroup. Nebulized GLY, combined with LABA, did not generate any additional safety signals.
Conclusion: Nebulized GLY demonstrated efficacy and was well tolerated up to 48 weeks in subjects with COPD with/without background LABA.
Keywords: COPD, nebulized glycopyrrolate, eFlow® CS, LAMA, background LABA
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