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

Br J Clin Pharmacol. 2017 Oct;83(10):2179-2194. doi: 10.1111/bcp.13316. Epub 2017 Jun 10.


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 One woman developed a drug rash and was withdrawn.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.

Keywords: biomarkers; drug development; pharmacodynamics; pharmacokinetics.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Anabolic Agents / adverse effects
  • Anabolic Agents / pharmacokinetics
  • Anabolic Agents / pharmacology*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Electrocardiography
  • Female
  • Half-Life
  • Healthy Volunteers
  • Heart / drug effects
  • Humans
  • Indoles / adverse effects
  • Indoles / pharmacokinetics
  • Indoles / pharmacology*
  • Lipoproteins, HDL / blood
  • Male
  • Middle Aged
  • Muscle Strength / drug effects*
  • Placebos
  • Postmenopause
  • Receptors, Androgen / metabolism*
  • Sex Factors
  • Sex Hormone-Binding Globulin / analysis
  • Young Adult


  • AR protein, human
  • Anabolic Agents
  • Indoles
  • Lipoproteins, HDL
  • Placebos
  • Receptors, Androgen
  • Sex Hormone-Binding Globulin
  • GSK2881078