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
| Autor: | Claire Maden, Jean Brooks, Jan van Noord, Jutta Beier, Suus Baggen, Anthony Cahn, Amanda Deans, Rashmi Mehta |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Time Factors bronchodilation Pilot Projects Placebos Electrocardiography Pulmonary Disease Chronic Obstructive Forced Expiratory Volume Bronchodilation Lung Salmeterol Xinafoate Original Research COPD Cross-Over Studies medicine.diagnostic_test LAMA General Medicine Tiotropium bromide respiratory system Middle Aged Bronchodilator Agents Europe Plethysmography Treatment Outcome Anesthesia Drug Therapy Combination Female Salmeterol hormones hormone substitutes and hormone antagonists medicine.drug circulatory and respiratory physiology Spirometry Scopolamine Derivatives LABA Muscarinic Antagonists International Journal of Chronic Obstructive Pulmonary Disease Placebo Drug Administration Schedule Administration Inhalation medicine Humans Albuterol Tiotropium Bromide Adrenergic beta-2 Receptor Agonists Aged business.industry Vital Signs Muscarinic antagonist dual therapy medicine.disease Crossover study respiratory tract diseases business |
| Zdroj: | International Journal of Chronic Obstructive Pulmonary Disease |
| ISSN: | 1178-2005 1176-9106 |
| Popis: | Jutta Beier1, Jan van Noord2, Amanda Deans3, Jean Brooks3, Claire Maden3, Suus Baggen4, Rashmi Mehta5, Anthony Cahn31INSAF Respiratory Research Institute, Germany; 2Atrium Medisch Centrum, The Netherlands; 3GlaxoSmithKline, Stockley Park, UK; 4GlaxoSmithKline, Zeist, The Netherlands; 5GlaxoSmithKline, RTP, NC, USABackground: 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 |
| Databáze: | OpenAIRE |
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