Selective androgen receptor modulation for muscle weakness in chronic obstructive pulmonary disease: a randomised control trial.

Selective androgen receptor modulators (SARMs) increase muscle mass via the androgen receptor. This phase 2A trial investigated the effects of a SARM, GSK2881078, in conjunction with exercise, on leg strength in patients with chronic obstructive pulmonary disease (COPD) and impaired physical function. 47 postmenopausal women and 50 men with COPD (forced expiratory volume in 1 s 30%–65% predicted; short physical performance battery score: 3–11) were enrolled into a randomised double-blind, placebo control trial. Patients were randomised 1:1 to once daily placebo or oral GSK2881078 (females: 1.0 mg; males: 2.0 mg) for 13 weeks with a concurrent home-exercise programme, involving strength training and physical activity. Primary endpoints were change from baseline in leg strength at 90 days (one-repetition maximum; absolute (kg) and relative (% change)) and multiple safety outcomes. Secondary endpoints included lean body mass, physical function and patient-reported outcomes. GSK2881078 increased leg strength in men. The difference in adjusted mean change from baseline and adjusted mean percentage change from baseline between treatment and placebo were: for women, 8.0 kg (90% CI −2.5 to 18.4) and 5.2% (90% CI −4.7 to 15.0), respectively; for men, 11.8 kg (90% CI −0.5 to 24.0) and 7.0% (90% CI 0.5 to 13.6), respectively. Lean body mass increased, but no changes in patient-reported outcomes were observed. Reversible reductions in high-density lipoprotein-cholesterol and transient elevations in hepatic transaminases were the main treatment-related safety findings. GSK2881078 was well tolerated and short-term treatment increased leg strength, when expressed as per cent predicted, in men with COPD more than physical training alone. NCT03359473.

选择性雄激素受体调节剂（SARMs）通过雄激素受体增加肌肉量。这项2A期试验研究了一种选择性雄激素受体调节剂GSK2881078联合运动对慢性阻塞性肺疾病（COPD）且身体功能受损患者腿部力量的影响。 47名绝经后女性和50名男性COPD患者（第1秒用力呼气量预计值为30% - 65%；简短体能测试评分：3 - 11）被纳入一项随机双盲、安慰剂对照试验。患者按1:1随机分组，分别接受每日一次的安慰剂或口服GSK2881078（女性：1.0毫克；男性：2.0毫克），持续13周，同时进行家庭锻炼计划，包括力量训练和体力活动。主要终点是90天时腿部力量较基线的变化（一次最大重复量；绝对值（千克）和相对值（变化百分比））以及多项安全性结果。次要终点包括瘦体重、身体功能和患者报告的结果。 GSK2881078增加了男性的腿部力量。治疗组与安慰剂组之间从基线调整后的平均变化差异以及从基线调整后的平均百分比变化差异分别为：女性，8.0千克（90%置信区间 -2.5至18.4）和5.2%（90%置信区间 -4.7至15.0）；男性，11.8千克（90%置信区间 -0.5至24.0）和7.0%（90%置信区间0.5至13.6）。瘦体重增加，但未观察到患者报告结果有变化。高密度脂蛋白胆固醇可逆性降低和肝转氨酶短暂升高是主要的与治疗相关的安全性发现。 GSK2881078耐受性良好，短期治疗在以预计值百分比表示时，对COPD男性腿部力量的增加比单独体育锻炼更显著。 NCT03359473。