Efficacy and safety of the long-acting muscarinic antagonist, GSK233705, delivered once-daily in patients with COPD

Authors


  • Authorship
    E Bateman participated in the running of the study and assisted with the preparation of the manuscript. G Feldman participated in the running of the study and commented on the manuscript. S Kilbride and J Brooks participated in the design of the study, were responsible for all statistical analyses and commented on the manuscript. S Harris participated in the running of the study, collected data, discussed findings and analyses, and commented on the manuscript. C Maden and G Crater participated in the design and running of the study, discussed findings and analyses, and commented on the manuscript. R Mehta was responsible for the pharmacokinetics for the study and commented on the manuscript.

  • Conflict of interest
    This study was funded by GSK, Stockley Park, UK. Sally Kilbride, Jean Brooks, Rashmi Mehta, Stephanie Harris, Claire Maden and Glenn Crater are employees of GSK. Eric Bateman has received lecture fees from AstraZeneca, Alk Abello, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Nycomed, Pfizer and TEVA, is a member of consultancy or advisory boards for Almirall, AlkAbello, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Forest, GlaxoSmithKline, Hoffmann la Roche, Napp, Novartis, Merck, Morria, Nycomed, Pfizer and has received industry-sponsored grants from Aeras, Almirall, Altana, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Hoffmann la Roche, Novartis, Merck, Morria, Nycomed, Pfizer.

  • There are no potential conflicts of interest for Gregory Feldman.

  • GSK study number AC2110664; clinical trials.gov NCT00676052.

  • This study has been reviewed by the appropriate ethics committee and been performed in accordance with the ethical standards laid down in the Declaration of Helsinki. All patients gave informed consent prior to any study related procedures taking place.

  • This is an Accepted Article that has been peer-reviewed and approved for publication in the The Clinical Respiratory Journal, but has yet to undergo copy-editing and proof correction. Please cite this article as an “Accepted Article”; doi: 10.1111/j.1752-699X.2012.00278.x

Professor E.D Bateman
Division of Pulmonology, Department of Medicine, University of Cape Town, George Street, Mowbray 7700, Cape Town, South Africa
Eric.bateman@uct.ac.za
Facsimile: +27 21 4066902
Telephone +27 21 4066901

Abstract

Introduction:  GSK233705 is a recently developed inhaled anticholinergic being investigated for the potential treatment of chronic obstructive pulmonary disease (COPD).

Objectives:  This dose-ranging, parallel-group, double-blind study compared the bronchodilator efficacy, safety and pharmacokinetics of GSK233705 with placebo in patients with moderate to severe COPD.

Methods:  Patients were randomised to receive 12.5µg, 25µg, 50µg, 100µg or 200µg of GSK233705 or placebo once-daily for 28 days. The primary endpoint was change from baseline in trough forced expiratory volume in one second (FEV1) on Day 29.

Results:  The Intent-to-treat population consisted of 576 patients (mean predicted FEV1 51%; mean age 62 years). Treatment with GSK233705 produced statistically significant improvements in pulmonary function compared with placebo. Only the 200µg dose exceeded the pre-defined target threshold of 130 mL difference compared with placebo for the primary endpoint of change from baseline in trough FEV1 on Day 29. No clear pattern of dose response was observed for the other doses. Serial FEV1 (0-24 hours) showed a peak effect around 2 hours post-dose and tended to decline to clinically insignificant levels compared with placebo at 23 and 24 hours.

Each dose of GSK233705 was well tolerated. The incidence of adverse events was low and similar across all treatment groups. There were no clinically significant effects on laboratory parameters, vital signs, or ECGs.

Conclusion:  All doses of GSK233705 demonstrated bronchodilatory activity and were well tolerated. Although the onset of bronchodilation was rapid, it was not sustained over 24 hours making it unsuitable for once-daily dosing.

Ancillary