Dataset from A Randomised, Double Blind, Placebo Controlled Study to Examine the Safety, Tolerability, Pharmacodynamics and Pharmacokinetic Profile of Single Inhaled Dry Powder Doses of GSK159802 in Healthy Male Subjects

GSK159802 is a potent, inhaled, long acting selective beta-2-receptor agonist (LABA), which is being developed for once daily treatment of asthma and COPD as part of a combination product with a once daily inhaled corticosteroid and also as a standalone product for the treatment of COPD. Stimulation of the beta-2-agonist in the lung mainly relaxes bronchial smooth muscle cells which results in bronchodilation. Unwanted systemic side effects related with beta-2-agonist treatment such as tachycardia, tremor, hyperglycemia and hypokalemia are limited by local administration and also tend to show tachyphylaxis. The LABAs that are currently available (e.g., salmeterol, formoterol) require twice-daily administration, given their duration of action. Therefore, there is significant opportunity for a once-daily inhaled medication to improve patient compliance and overall disease management by providing sustained, 24-hour bronchodilation.

GSK159802是一种强效、吸入用长效选择性β2受体激动剂（long acting selective beta-2-receptor agonist, LABA），目前正被开发为与每日一次吸入型糖皮质激素联用的复方制剂，用于哮喘与慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）的每日一次治疗；同时也可作为单药制剂用于COPD的治疗。肺部β2受体激动剂的刺激作用主要可松弛支气管平滑肌细胞，进而引发支气管舒张。与β2受体激动剂治疗相关的全身性不良反应（如心动过速、震颤、高血糖与低钾血症），可通过局部给药方式得到缓解，且此类不良反应易产生快速耐受性（tachyphylaxis）。目前已上市的LABA类药物（如沙美特罗、福莫特罗）由于作用持续时间的限制，需要每日两次给药。因此，开发可每日一次吸入给药的药物，通过提供持续24小时的支气管舒张效果，可显著提升患者用药依从性并优化整体疾病管理。