The online version of this article (doi:10.1186/1465-9921-15-78) contains supplementary material, which is available to authorized users.
JFD is a consultant and advisor for Boehringer Ingelheim, Forest, GlaxoSmithKline, Mylan, Novartis, Sunovion, and is a consultant for PneumRx on the data safety monitoring board. DN has received fees from AstraZeneca, Boehringer Ingelheim, Forest Research, GlaxoSmithKline, Merck, and Novartis for serving on advisory boards or endpoint committees of clinical trials. JB, DO, and AC are employees of GlaxoSmithKline and hold stocks/shares in the company.
JFD and DN were involved in the conduct of the study, and the review and interpretation of the data, JB provided statistical input and analysis, and was involved in the review and interpretation of the data. DO and AC were involved in the planning and conduct of the study, and the review and interpretation of the data. All authors provided intellectual and critical input, contributed to the writing of the paper, and read and approved the final manuscript.
The long-acting muscarinic antagonist (LAMA) umeclidinium (UMEC) and the combination of UMEC with the long-acting β2-agonist (LABA) vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD) in the US and EU. They are not indicated for the treatment of asthma.
In this 52-week, double-blind, placebo-controlled, parallel-group safety study (GSK study DB2113359; NCT01316887), patients were randomized 2:2:1 to UMEC/VI 125/25 mcg, UMEC 125 mcg, or placebo. Study endpoints included adverse events (AEs), clinical chemistry and hematology parameters, vital signs, 12-lead, and 24-hour Holter electrocardiograms. COPD exacerbations and rescue medication use were assessed as safety parameters; lung function was also evaluated.
The incidence of on-treatment AEs, serious AEs (SAEs), and drug-related AEs was similar between treatment groups (AEs: 52–58%; SAEs: 6–7%; drug-related AEs: 12–13%). Headache was the most common AE in each treatment group (8–11%). AEs associated with the LAMA and LABA pharmacologic classes occurred at a low incidence across treatment groups. No clinically meaningful effects on vital signs or laboratory assessments were reported for active treatments versus placebo. The incidences of atrial arrhythmias with UMEC/VI 125/25 mcg were similar to placebo; for UMEC 125 mcg, the incidences of ectopic supraventricular beats, sustained supraventricular tachycardia, and ectopic supraventricular rhythm were ≥2% greater than placebo. With active treatments, COPD exacerbations were fewer (13–15% of patients reporting ≥1 exacerbation) and on average less rescue medication was required (1.6–2.2 puffs/day) versus placebo (24% reporting ≥1 exacerbation, 2.6 puffs/day). Both active treatments improved lung function versus placebo.
UMEC/VI 125/25 mcg and UMEC 125 mcg were well tolerated over 12 months in patients with COPD.
Additional file 1: Table S1: Prohibited medications prior to Visit 1, by time interval. Table S2. Summary of ECG abnormalities meeting the withdrawal criteria. Table S3. Summary of Holter abnormalities meeting the withdrawal criteria. (DOC 87 KB)
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- Safety and tolerability of once-daily umeclidinium/vilanterol 125/25 mcg and umeclidinium 125 mcg in patients with chronic obstructive pulmonary disease: results from a 52-week, randomized, double-blind, placebo-controlled study
James F Donohue
- BioMed Central
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