Efficacy and Safety of umeclidinium/vilanterol 62.5/25 MCG and Tiotropium 18 MCG in Chronic Obstructive Pulmonary Disease: Results of a 24-week, Randomized, Controlled Trial

Respir Med. 2014 Dec;108(12):1752-60. doi: 10.1016/j.rmed.2014.10.002.

Abstract

Background: Combinations of inhaled long-acting bronchodilator therapies such as muscarinic antagonists and β2-agonists may be more effective than monotherapy in the treatment of chronic obstructive pulmonary disease (COPD).

Methods: This study was a 24-week, Phase III, multicenter, randomized, blinded, double-dummy, parallel-group study of the once-daily, inhaled, fixed-dose combination of the long-acting muscarinic antagonist umeclidinium bromide and the long-acting β2-agonist vilanterol (UMEC/VI 62.5/25 mcg) versus tiotropium (TIO, 18 mcg). The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at Day 169. The secondary endpoint was weighted mean FEV1 over 0–6 h post-dose at Day 168. For key endpoints, a step-down closed testing hierarchy was applied to account for multiplicity. Other efficacy and safety endpoints were assessed.

Results: Statistically significant improvements in trough FEV1 at Day 169 (0.112 L, 95% confidence interval [CI]: 0.081, 0.144; p < 0.001) and weighted mean FEV1 over 0–6 h post-dose at Day 168 (0.105 L, 95% CI: 0.071, 0.140; p < 0.001) were observed for UMEC/VI versus TIO. In addition UMEC/VI improved health-related quality of life, and reduced requirement for the use of rescue medication compared with TIO. The incidence of adverse events was similar between treatment groups.

Conclusions: UMEC/VI was associated with statistically significant and clinically meaningful improvements in lung function versus TIO. UMEC/VI was well tolerated. UMEC/VI 62.5/25 mcg could provide an effective new treatment option for patients with moderate-to-very severe 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
  • Benzyl Alcohols / therapeutic use*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / therapeutic use*
  • Chlorobenzenes / administration & dosage
  • Chlorobenzenes / adverse effects
  • Chlorobenzenes / therapeutic use*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Disease, Chronic Obstructive / rehabilitation
  • Quality of Life
  • Quinuclidines / administration & dosage
  • Quinuclidines / adverse effects
  • Quinuclidines / therapeutic use*
  • Scopolamine Derivatives / administration & dosage
  • Scopolamine Derivatives / adverse effects
  • Scopolamine Derivatives / therapeutic use*
  • Tiotropium Bromide
  • Treatment Outcome

Substances

  • Benzyl Alcohols
  • Bronchodilator Agents
  • Chlorobenzenes
  • Drug Combinations
  • GSK573719
  • Quinuclidines
  • Scopolamine Derivatives
  • vilanterol
  • Tiotropium Bromide