A new class of bronchodilator improves lung function in COPD: a trial with GSK961081

Pascal L M L Wielders, Andrea Ludwig-Sengpiel, Nicholas Locantore, Suus Baggen, Robert Chan, John H Riley, Pascal L M L Wielders, Andrea Ludwig-Sengpiel, Nicholas Locantore, Suus Baggen, Robert Chan, John H Riley

Abstract

GSK961081 is a bifunctional molecule demonstrating both muscarinic antagonist and β-agonist activities. This was a 4-week, multicentre, randomised, double-blind, double-dummy, placebo and salmeterol controlled parallel group study. Doses ranging across three twice-daily doses and three once-daily doses were assessed in moderate and severe chronic obstructive pulmonary disease (COPD) patients. Trough forced expiratory volume in 1 s (FEV1) at day 29 was the primary end-point. At days 1 and 28, 12-h FEV1 spirometry was performed in all patients. A subset of patients underwent complete 24-h spirometry at day 28. The study recruited 436 patients. GSK961081 showed statistically and clinically significant differences from placebo in all doses and regimens for trough FEV1 on day 29 (155-277 mL). The optimal total daily dose was 400 μg, either as 400 μg once daily or as 200 μg twice daily, with an improvement in day 29 trough FEV1 of 215 mL and 249 mL, respectively. Other efficacy end-points also showed improvement. No effects were observed on glucose, potassium, heart rate, blood pressure and no dose-response effect was seen on corrected QT elongation. This study showed that GSK961081 is an effective bronchodilator in COPD and appeared to be safe and well tolerated.

Trial registration: ClinicalTrials.gov NCT01319019.

Conflict of interest statement

Conflict of interest: Disclosures can be found alongside the online version of this manuscript at www.erj.ersjournals.com

Figures

Figure 1–
Figure 1–
Subject disposition consort diagram. ITT: intent-to-treat; BD: twice daily; OD: once daily; DCC: did not meet continuation criteria; AE: adverse event; PSC: protocol-defined stopping criteria; PD: protocol deviation; WC: withdrew consent; LoE: lack of efficacy; ID: investigator discretion; LTFU: lost to follow-up. #: 437 subjects were randomised, but one subject did not receive any randomised medication, leaving 436 for the ITT population.
Figure 2–
Figure 2–
Serial forced expiratory volume in 1 s (FEV1) profile over 0–24 h on day 28 in the subset of overnight subjects. a) Once daily dosage regimen; b) twice daily dosage regimen.
Figure 3–
Figure 3–
Serial forced expiratory volume in 1 s (FEV1) profile over 0–12 h on a) day 1 and b) day 28, in all subjects.

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Source: PubMed

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