Once daily glycopyrronium for the treatment of COPD: pooled analysis of the GLOW1 and GLOW2 studies

Abstract

Background:

Glycopyrronium is a once daily (o.d.) long-acting muscarinic antagonist that is approved for maintenance treatment of COPD. This post-hoc pooled analysis of two phase III studies, GLycopyrronium bromide in COPD airWays 1 and 2 (GLOW1 and GLOW2), evaluated the effects of glycopyrronium compared with placebo and tiotropium over 26–52 weeks in patients with moderate-to-severe COPD.

Methods:

Patients aged ≥40 years were randomised to 26 weeks’ treatment with glycopyrronium 50 μg o.d. or placebo (GLOW1) or 52 weeks’ treatment with glycopyrronium 50 μg o.d., placebo, or open-label tiotropium 18 μg o.d. (GLOW2). The primary efficacy endpoint in both studies was trough forced expiratory volume in one second (FEV₁) at Week 12. Other outcomes included additional spirometry endpoints, moderate or severe exacerbations, dyspnoea, health status, rescue medication use and safety. Serial spirometry over 24 hours was conducted in a subset of patients.

Results:

Of 1888 subjects randomised, 98.2% were analysed (glycopyrronium 1059, tiotropium 267, placebo 528). Least squares mean (LSM) trough FEV₁ was significantly higher with glycopyrronium versus placebo at Week 12 (treatment difference ± standard error [SE]: 103 ± 11.2 mL; p < 0.001), as well as at Day 1 and Weeks 26 and 52. More patients achieved ≥100 mL increase in trough FEV₁ from baseline with glycopyrronium versus placebo at all assessments (p < 0.001). Glycopyrronium significantly improved FEV₁ immediately after the first dose on Day 1 versus placebo (90 mL at 5 minutes, 144 mL at 15 minutes; both p < 0.001) and versus tiotropium (43 mL at 5 minutes, 65 mL at 15 minutes; both p < 0.001). Glycopyrronium significantly improved other spirometry endpoints and provided clinically meaningful 24 hour bronchodilation versus placebo at most timepoints from Day 1 onwards (p < 0.05). Time to first moderate or severe exacerbation was significantly prolonged with glycopyrronium versus placebo over 26 and 52 weeks (36% and 33%, respectively; both p < 0.001). Glycopyrronium provided significantly greater relief of dyspnoea, improved health status and reduced rescue medication use versus placebo. Glycopyrronium was safe and well tolerated.

Conclusions:

Glycopyrronium 50 μg o.d. provided early bronchodilation after the first dose that was sustained for 24 hours, and reduced the risk of exacerbations compared with placebo, with efficacy at least equivalent to tiotropium.

Trial Registrations:

NCT01005901 and NCT00929110.

Keywords::

• Bronchodilation
• Exacerbations
• Glycopyrronium
• LAMA
• Once daily

Transparency

Declaration of funding

This article was sponsored by Novartis.

Author contributions: A.D. was involved in acquisition of data, analysis and interpretation of data for the GLOW1 study. E.K. was involved in acquisition of data, analysis and interpretation of data for the GLOW2 study. T.O. participated in the development of the design and concept of the studies and in the interpretation of the data. All authors had full access to the data and read and approved the final manuscript.

Declaration of financial/other relationships

A.D. has received research, consulting and lecturing fees from GlaxoSmithKline, Sepracor, Schering Plough, Altana, Methapharma, AstraZeneca, ONO pharma, Merck Canada, Forest Laboratories, Novartis Canada/USA, Boehringer Ingelheim (Canada) Ltd, Pfizer Canada, SkyePharma, and KOS Pharmaceuticals. E.K. has served on speaker panels or advisory boards for AstraZeneca (MAP Pharma), Dey Laboratories, GlaxoSmithKline, Ironwood Pharmaceuticals, Merck (Schering Plough), Pfizer, Sanofi Aventis, Sunovion, Targacept, Teva Labs and UCB Pharma. He has conducted clinical research trials for fifty pharmaceutical companies, including Novartis and Boehringer Ingelheim. T.O., P.D., H.C. and P.G. are employees of Novartis.

CMRO peer reviewers on this manuscript have received honoraria for their review work, but have no other relevant financial relationships to disclose.

Acknowledgements

The authors were assisted in the preparation of the manuscript by Shelley Davis and Tamsin Williamson, medical writers contracted to CircleScience (Macclesfield, UK), and Mark J Fedele (Novartis). Writing support was funded by Novartis.