Pharmacodynamics of GSK961081, a bi-functional molecule, in patients with COPD

Eric D Bateman; Oliver Kornmann; Claire Ambery; Virginia Norris

doi:10.1016/j.pupt.2013.03.015

Pharmacodynamics of GSK961081, a bi-functional molecule, in patients with COPD

Pulm Pharmacol Ther. 2013 Oct;26(5):581-7. doi: 10.1016/j.pupt.2013.03.015. Epub 2013 Mar 26.

Authors

Eric D Bateman¹, Oliver Kornmann, Claire Ambery, Virginia Norris

Affiliation

¹ University of Cape Town Lung Institute, George Street, Mowbray 7700, Cape Town, South Africa. Eric.Bateman@uct.ac.za

PMID: 23538170
DOI: 10.1016/j.pupt.2013.03.015

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.

Publication types

Comparative Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adrenergic beta-2 Receptor Agonists / administration & dosage
Adrenergic beta-2 Receptor Agonists / adverse effects
Adrenergic beta-2 Receptor Agonists / therapeutic use
Adult
Aged
Albuterol / administration & dosage
Albuterol / adverse effects
Albuterol / analogs & derivatives*
Albuterol / therapeutic use
Bronchodilator Agents / administration & dosage
Bronchodilator Agents / adverse effects
Bronchodilator Agents / therapeutic use*
Carbamates / administration & dosage
Carbamates / adverse effects
Carbamates / therapeutic use*
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Drug Therapy, Combination
Female
Forced Expiratory Volume
Humans
Male
Middle Aged
Muscarinic Antagonists / administration & dosage
Muscarinic Antagonists / adverse effects
Muscarinic Antagonists / therapeutic use
Pulmonary Disease, Chronic Obstructive / drug therapy*
Pulmonary Disease, Chronic Obstructive / physiopathology
Quinolones / administration & dosage
Quinolones / adverse effects
Quinolones / therapeutic use*
Salmeterol Xinafoate
Scopolamine Derivatives / administration & dosage
Scopolamine Derivatives / adverse effects
Scopolamine Derivatives / therapeutic use*
Time Factors
Tiotropium Bromide
Treatment Outcome

Substances

Adrenergic beta-2 Receptor Agonists
Bronchodilator Agents
Carbamates
Muscarinic Antagonists
Quinolones
Scopolamine Derivatives
batefenterol
Salmeterol Xinafoate
Albuterol
Tiotropium Bromide