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

• Published in: The European respiratory journal Vol. 42; no. 4; pp. 972 - 981
• Main Authors: WIELDERS, Pascal L. M. L, LUDWIG-SENGPIEL, Andrea, LOCANTORE, Nicholas, BAGGEN, Suus, CHAN, Robert, RILEY, John H
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.10.2013; European Respiratory Society
• Subjects: Aged; Albuterol - administration & dosage; Albuterol - analogs & derivatives; Albuterol - therapeutic use; Biological and medical sciences; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - therapeutic use; Carbamates - administration & dosage; Carbamates - therapeutic use; Chronic obstructive pulmonary disease, asthma; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Male; Medical sciences; Middle Aged; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - therapeutic use; Original; Patient Safety; Pneumology; Pulmonary Disease, Chronic Obstructive - drug therapy; Quinolones - administration & dosage; Quinolones - therapeutic use; Salmeterol Xinafoate; Smoking - adverse effects; Spirometry - methods; Treatment Outcome; Lung disease; Improvement; Chronic; Lung function; Respiratory disease; Bronchodilator; Bronchus disease; Clinical trial; Chronic obstructive pulmonary disease; Obstructive pulmonary disease
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.00165712

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.