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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.

Abstract

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 (FEV(1)) 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 FEV(1) was 55% at screening. Compared with placebo (n = 24), the adjusted mean change from baseline in trough FEV(1) 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.

Authors+Show Affiliations

INSAF Respiratory Research Institute, Germany. j.beier@insaf-wi.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22419863

Citation

Beier, Jutta, et al. "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." International Journal of Chronic Obstructive Pulmonary Disease, vol. 7, 2012, pp. 153-64.
Beier J, van Noord J, Deans A, et al. 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. Int J Chron Obstruct Pulmon Dis. 2012;7:153-64.
Beier, J., van Noord, J., Deans, A., Brooks, J., Maden, C., Baggen, S., Mehta, R., & Cahn, A. (2012). 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. International Journal of Chronic Obstructive Pulmonary Disease, 7, 153-64. https://doi.org/10.2147/COPD.S26100
Beier J, et al. 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. Int J Chron Obstruct Pulmon Dis. 2012;7:153-64. PubMed PMID: 22419863.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Beier,Jutta, AU - van Noord,Jan, AU - Deans,Amanda, AU - Brooks,Jean, AU - Maden,Claire, AU - Baggen,Suus, AU - Mehta,Rashmi, AU - Cahn,Anthony, Y1 - 2012/03/05/ PY - 2012/3/16/entrez PY - 2012/3/16/pubmed PY - 2012/6/26/medline KW - COPD KW - LABA KW - LAMA KW - bronchodilation KW - dual therapy SP - 153 EP - 64 JF - International journal of chronic obstructive pulmonary disease JO - Int J Chron Obstruct Pulmon Dis VL - 7 N2 - 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 (FEV(1)) 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 FEV(1) was 55% at screening. Compared with placebo (n = 24), the adjusted mean change from baseline in trough FEV(1) 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. SN - 1178-2005 UR - https://www.unboundmedicine.com/medline/citation/22419863/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_ L2 - https://dx.doi.org/10.2147/COPD.S26100 DB - PRIME DP - Unbound Medicine ER -