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

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.

Figure 1

Study design. ^aOne patient was randomized in error but did not receive study drug. UMEC, umeclidinium; VI, vilanterol.

Figure 2

AEs in the ITT population. *Includes on-treatment and post-treatment AEs. AE, adverse event; ITT, intent-to-treat; SAE, serious AE; UMEC, umeclidinium; VI, vilanterol. Patient numbers are indicated above bars.

Figure 3

On-treatment AEs and SAEs. On-treatment AEs reported by ≥4% of patients in any treatment group and SAEs reported by ≥1% of patients in any treatment group in the ITT population. AE, adverse event; COPD, chronic obstructive pulmonary disease; ITT, intent-to-treat; SAE, serious AE; UMEC, umeclidinium; VI, vilanterol. Patient numbers are indicated above bars.

Figure 4

LS mean change from baseline in trough FEV₁ (A) and FVC (B). CI, confidence interval; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; LS, least squares; UMEC, umeclidinium; VI, vilanterol.

Figure 5

Time to first COPD exacerbation. COPD, chronic obstructive pulmonary disease; UMEC, umeclidinium; VI, vilanterol.