COPD is a growing health issue. As life-long smokers age, they are more likely to develop COPD in the form of emphysema or chronic bronchitis, or even both. The US National Heart, Lung and Blood Institute estimates that more than 8% of the US population have some form of COPD, caused by long-term exposure to substances that irritate the lung, with cigarette smoke being the main culprit.
Successful treatment options remain limited, and the long-acting antimuscarinic agent umeclidinium is a new drug from GlaxoSmithKline that has just been approved to treat COPD, both as a single agent and in combination with the recently approved long-acting beta-2 agonist drug vilanterol.1 Both of these are administered via dry powder inhaler.
Numerous clinical trials have been carried out, both on umeclidinium as a single agent, and in the combination. In one randomised, double blind, placebo-controlled, parallel group study, 285 patients with COPD were given once-daily doses of 125, 250 or 500µg of umeclidinium for 28 days.2 All doses significantly increased trough forced expiratory volume (FEV), with reductions in salbutamol use. It was well tolerated.
In another three-way crossover trial, five different daily doses of umeclidinium ranging from 62.5 to 1000µg, three twice daily doses of 62.5–250µg, or placebo, and open label tiotropium, were given to 176 patients for 14 days.3 Once daily dosing was more successful with lower rescue salbutamol use, and improvements over placebo were seen across all doses.
A further randomised, placebo controlled trial in 246 patients with COPD involved once daily doses of 62.5 and 125µg for 12 weeks.4 At the end of the 12 week period, both doses significantly improved least squares mean change from baseline in trough FEV in one second (FEV1) compared with placebo. There were few adverse events, and these were similar across all patient groups.
Several trials were also carried out that dosed umeclidinium in combination with vilanterol. In one double blind, placebo-controlled, parallel group trial, 1532 patients with COPD were randomised to received 62.5µg umeclidinium, 25µg vilanterol, both these doses in combination, or placebo.5 All non-placebo groups had statistically significant improvements in FEV1 compared with placebo after 24 weeks. Significantly greater improvements were seen in those patients who received the combination than either of the monotherapies.
In a similar trial, only using 125µg doses of umeclidinium in place of 62.5µg doses,6 a total of 1493 patients were enrolled. Again all active treatments gave significant improvements in FEV1 over placebo, and results were better for the combination than either agent alone. No safety signals were seen.
References
1. M. Salmon et al. J. Pharmacol. Exp. Ther. 2013, 345, 260
2. M. Decramer et al. Respir. Physiol. Neurobiol. 2013, 185, 393
3. J.F. Donohue et al. Respir. Med. 2012, 106, 970
4. R. Trivedi et al. Eur. Respir. J. 2014, 43, 72
5. J.F. Donohue et al. Respir. Med. 2013, 107, 1538
6. B. Celli et al. Chest 2014, epub ahead of print
