Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD

Respir Med. 2013 Oct;107(10):1538-46. doi: 10.1016/j.rmed.2013.06.001. Epub 2013 Jul 2.

Abstract

Study objective: To examine the efficacy and safety of the once-daily, inhaled, long-acting muscarinic antagonist/β2-agonist combination umeclidinium/vilanterol (UMEC/VI) compared with UMEC and VI monotherapies in patients with chronic obstructive pulmonary disease (COPD).

Methods: In this 24-week, double-blind, placebo-controlled, parallel-group study (ClinicalTrials.gov: NCT01313650) eligible patients were randomised 3:3:3:2 to treatment with UMEC/VI 62.5/25 mcg, UMEC 62.5 mcg, VI 25 mcg or placebo administered once daily via dry powder inhaler (N = 1532; intent-to-treat population). Primary endpoint was trough forced expiratory volume in one second (FEV1) on Day 169 (23-24 h post-dose). Additional lung-function, symptomatic, and health-related quality-of-life endpoints were assessed, including 0-6 h weighted-mean FEV1, rescue salbutamol use, Transition Dyspnoea Index (TDI), Shortness Of Breath With Daily Activity (SOBDA) and St. George's Respiratory Questionnaire (SGRQ) scores. Safety evaluations included adverse events (AEs), vital signs, 12-lead/24-h Holter electrocardiography parameters and clinical laboratory/haematology measurements.

Results: All active treatments produced statistically significant improvements in trough FEV1 compared with placebo on Day 169 (0.072-0.167 L, all p < 0.001); increases with UMEC/VI 62.5/25 mcg were significantly greater than monotherapies (0.052-0.095 L, p ≤ 0.004). Improvements were observed for UMEC/VI 62.5/25 mcg vs placebo for weighted-mean FEV1 on Day 168 (0.242 L, p < 0.001), rescue salbutamol use during Weeks 1-24 (-0.8 puffs/day, p = 0.001), TDI (1.2 units, p < 0.001), SOBDA (-0.17 units, p < 0.001) and SGRQ (-5.51 units, p < 0.001) scores. No clinically-significant changes in vital signs, electrocardiography, or laboratory parameters were observed.

Conclusion: Once-daily UMEC/VI 62.5/25 mcg was well tolerated and provided clinically-significant improvements in lung function and symptoms in patients with COPD.

Keywords: COPD; Fixed-dose combination; Long-acting bronchodilator; Muscarinic antagonist; Randomised; β-agonist.

Publication types

  • 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 Administration Schedule
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Quality of Life
  • Quinuclidines / administration & dosage
  • Quinuclidines / adverse effects
  • Quinuclidines / therapeutic use*
  • Severity of Illness Index
  • Treatment Outcome
  • Vital Capacity / drug effects

Substances

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

Associated data

  • ClinicalTrials.gov/NCT01313650