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

Respir Res. 2014 Jul 11;15(1):78. doi: 10.1186/1465-9921-15-78.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: UMEC/VI 125/25 mcg and UMEC 125 mcg were well tolerated over 12 months in patients with COPD.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Benzyl Alcohols / administration & dosage*
  • Benzyl Alcohols / adverse effects*
  • Chlorobenzenes / administration & dosage*
  • Chlorobenzenes / adverse effects*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Quinuclidines / administration & dosage*
  • Quinuclidines / adverse effects*

Substances

  • Benzyl Alcohols
  • Chlorobenzenes
  • Drug Combinations
  • GSK573719
  • Quinuclidines
  • vilanterol