Safety, pharmacokinetics and pharmacological effects of the selective androgen receptor modulator, GSK2881078, in healthy men and postmenopausal women

Aim Selective androgen receptor modulators (SARMs) induce anabolic effects on muscle without the adverse effects of androgenic steroids. In this first‐in‐human study, we report the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of the SARM GSK2881078. Methods In Part A, healthy young men (n = 10) received a single dose of study drug (0 mg, 0.05 mg, 0.1 mg, 0.2 mg GSK2881078 or matching‐placebo). In Part B, repeat‐dose cohorts in men (n = 65) were 0.05 mg, 0.2 mg then 0.08 mg, 0.24 mg, 0.48 mg, 0.75 mg, or placebo; in women (n = 24) they were 0.24 mg, 0.35 mg, or placebo (7 days for 0.5 mg, 14 days for other doses). Results PK analysis showed dose‐proportional increases in exposure and a long >100‐h half‐life. No significant effects on vital signs, electrocardiograms, cardiac telemetry or standard clinical laboratory studies were observed. A dose–response effect was observed on lowering both high‐density lipoprotein and sex hormone‐binding globulin. In females at 0.35 mg, differences from placebo were −0.518 (95% confidence interval: –0.703, −0.334) mmol l–1 and −39.1 (−48.5, −29.7) nmol l–1, respectively. Women showed greater sensitivity to these parameters at lower doses than men. Drug‐related adverse events (AEs) were mild. One woman developed a drug rash and was withdrawn. Two men had elevated creatine phosphokinase after physical exertion during follow‐up. A serious AE occurred in a subject on placebo. Conclusions These data demonstrate pharmacodynamic effects with acceptable tolerability and support further clinical evaluation of this SARM.