Back to Journals » International Journal of Chronic Obstructive Pulmonary Disease » Volume 7

Safety and efficacy of dual therapy with GSK233705 and salmeterol versus monotherapy with salmeterol, tiotropium, or placebo in a crossover pilot study in partially reversible COPD patients

Authors Beier J, van Noord J, Deans, Brooks, Maden, Baggen S, Mehta R, Cahn A

Received 12 September 2011

Accepted for publication 19 November 2011

Published 5 March 2012 Volume 2012:7 Pages 153—164

DOI https://doi.org/10.2147/COPD.S26100

Review by Single-blind

Peer reviewer comments 3

Jutta Beier1, Jan van Noord2, Amanda Deans3, Jean Brooks3, Claire Maden3, Suus Baggen4, Rashmi Mehta5, Anthony Cahn3

1INSAF Respiratory Research Institute, Germany; 2Atrium Medisch Centrum, The Netherlands; 3GlaxoSmithKline, Stockley Park, UK; 4GlaxoSmithKline, Zeist, The Netherlands; 5GlaxoSmithKline, RTP, NC, USA

Background: GSK233705 is an inhaled, long-acting muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). This study was performed to see if the addition of GSK233705 to salmeterol would provide greater bronchodilation than salmeterol or tiotropium alone in COPD.
Methods: In an incomplete-block, three-period, crossover design, dually responsive patients received three of the following five treatments: GSK233705 20 µg plus salmeterol 50 µg twice-daily; GSK233705 50 µg plus salmeterol 50 µg twice-daily; salmeterol 50 µg or placebo, each twice-daily; and tiotropium 18 µg or placebo once-daily for 7 days. Each treatment period was separated by a 14-day washout. The primary efficacy endpoint was morning (trough) forced expiratory volume in 1 second (FEV1) on Day 8, following 7 days of treatment. Secondary endpoints included pulmonary function, plethysmography, pharmacokinetics of GSK233705 and salmeterol, adverse events (AEs), electrocardiograms (ECGs), vital signs, and laboratory parameters.
Results: A total of 47 patients were randomized. The mean % predicted normal postbronchodilator FEV1 was 55% at screening. Compared with placebo (n = 24), the adjusted mean change from baseline in trough FEV1 on Day 8 was 215 mL higher with GSK233705 20 µg + salmeterol (n = 23) and 203 mL higher with GSK233705 50 µg + salmeterol (n = 27), whereas with salmeterol (n = 27) and tiotropium (n = 28) the changes were 101 mL and 118 mL higher, respectively. The primary efficacy results were supported by the results from the other secondary lung function assessments. AEs were reported by similar proportions of patients across the treatment groups, with headache the most frequently reported treatment-related AE reported by one subject receiving each of GSK233705 20 µg + salmeterol, tiotropium, and placebo. No significant differences were seen in vital signs, ECGs, or laboratory parameters between the groups.
Conclusion: The addition of GSK233705 to salmeterol in partially reversible COPD patients resulted in greater bronchodilation than salmeterol or tiotropium alone and was well tolerated.

Keywords: COPD, bronchodilation, dual therapy, LAMA, LABA

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Fibrinogen, chronic obstructive pulmonary disease (COPD) and outcomes in two United States cohorts

Valvi D, Mannino DM, Müellerova H, Tal-Singer R

International Journal of Chronic Obstructive Pulmonary Disease 2012, 7:173-182

Published Date: 7 March 2012

Relationships between respiratory and airway resistances and activity-related dyspnea in patients with chronic obstructive pulmonary disease

Mahut B, Caumont-Prim A, Plantier L, Gillet-Juvin K, Callens E, Sanchez O, Chevalier-Bidaud B, Bokov P, Delclaux C

International Journal of Chronic Obstructive Pulmonary Disease 2012, 7:165-171

Published Date: 6 March 2012

Topiramate and the vision: a systematic review

Abtahi MA, Abtahi SH, Fazel F, Roomizadeh P, Etemadifar M, Jenab K, Akbari M

Clinical Ophthalmology 2012, 6:117-131

Published Date: 12 January 2012

Pain relief in labor: a survey of awareness, attitude, and practice of health care providers in Zaria, Nigeria

Ogboli-Nwasor E, Adaji SE, Bature SB, Shittu OS

Journal of Pain Research 2011, 4:227-232

Published Date: 17 August 2011

Multidisciplinary management of type 2 diabetes in children and adolescents

Michael E Bowen, Russell L Rothman

Journal of Multidisciplinary Healthcare 2010, 3:113-124

Published Date: 28 July 2010

Correlation between the matrix metalloproteinase-9 activity and chondroitin sulfate concentrations in tear fluid after laser in situ keratomileusis

Tetsuya Mutoh, Masaya Nishio, Yukihiro Matsumoto, et al

Clinical Ophthalmology 2010, 4:823-828

Published Date: 20 July 2010

Personality of mothers of substance-dependent patients

David Baron, Samir AbolMagd, Salwa Erfan, et al

Journal of Multidisciplinary Healthcare 2010, 3:29-32

Published Date: 28 April 2010

Advances in the treatment of Raynaud’s phenomenon

Terri L Levien

Vascular Health and Risk Management 2010, 6:167-177

Published Date: 11 March 2010