Abstract
GSK961081 is an inhaled bi-functional molecule with both muscarinic antagonism and β2-agonism (MABA) properties. This randomised, double-blind, double-dummy, crossover study evaluated 14 days treatment with the MABA GSK961081 400 μg and 1200 μg once daily and tiotropium 18 μg once daily plus salmeterol 50 μg twice daily (TIO + SAL), versus placebo in 50 patients with moderate COPD. The primary endpoint was forced expiratory volume in 1 s (FEV1) at 24 h on Days 1 and 14. MABA 400 (n = 29), MABA 1200 (n = 32) and TIO + SAL (n = 41) resulted in significant increases in FEV1 over 24 h. Mean (95% CI) 24 h trough FEV1 (L) values relative to placebo (n = 43) were, for Day 1, MABA 400: 0.141 (0.060, 0.222); MABA 1200: 0.184 (0.105, 0.263); TIO + SAL: 0.162 (0.092, 0.231); for Day 14, MABA 400: 0.115 (0.024, 0.205); MABA 1200: 0.168 (0.080, 0.255); TIO + SAL: 0.103 (0.026, 0.180). Onset of bronchodilation was faster for both MABA doses versus TIO + SAL. No clinically relevant systemic pharmacodynamic effects were observed. Adverse events were similar across groups; however tremor (n = 2, MABA 1200), dysgeusia (n = 2, MABA 1200; n = 2, MABA 400) and dry mouth (n = 1, MABA 1200) were reported after GSK961081 only. GSK961081 demonstrated sustained bronchodilation similar to TIO + SAL, but with a more rapid onset, and was well tolerated at the tested doses.
Keywords:
Bi-functional molecule; COPD; MABA.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Comparative Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic beta-2 Receptor Agonists / administration & dosage
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Adrenergic beta-2 Receptor Agonists / adverse effects
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Adrenergic beta-2 Receptor Agonists / therapeutic use
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Adult
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Aged
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Albuterol / administration & dosage
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Albuterol / adverse effects
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Albuterol / analogs & derivatives*
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Albuterol / therapeutic use
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Bronchodilator Agents / administration & dosage
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Bronchodilator Agents / adverse effects
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Bronchodilator Agents / therapeutic use*
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Carbamates / administration & dosage
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Carbamates / adverse effects
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Carbamates / therapeutic use*
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Cross-Over Studies
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Dose-Response Relationship, Drug
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Double-Blind Method
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Drug Therapy, Combination
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Female
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Forced Expiratory Volume
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Humans
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Male
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Middle Aged
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Muscarinic Antagonists / administration & dosage
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Muscarinic Antagonists / adverse effects
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Muscarinic Antagonists / therapeutic use
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Pulmonary Disease, Chronic Obstructive / drug therapy*
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Pulmonary Disease, Chronic Obstructive / physiopathology
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Quinolones / administration & dosage
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Quinolones / adverse effects
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Quinolones / therapeutic use*
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Salmeterol Xinafoate
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Scopolamine Derivatives / administration & dosage
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Scopolamine Derivatives / adverse effects
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Scopolamine Derivatives / therapeutic use*
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Time Factors
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Tiotropium Bromide
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Treatment Outcome
Substances
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Adrenergic beta-2 Receptor Agonists
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Bronchodilator Agents
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Carbamates
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Muscarinic Antagonists
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Quinolones
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Scopolamine Derivatives
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batefenterol
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Salmeterol Xinafoate
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Albuterol
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Tiotropium Bromide