PMID- 28449232
OWN - NLM
STAT- MEDLINE
DCOM- 20180604
LR  - 20240326
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 83
IP  - 10
DP  - 2017 Oct
TI  - Safety, pharmacokinetics and pharmacological effects of the selective androgen 
      receptor modulator, GSK2881078, in healthy men and postmenopausal women.
PG  - 2179-2194
LID - 10.1111/bcp.13316 [doi]
AB  - 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 One woman developed a drug rash and was withdrawn.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.
CI  - (c) 2017 The British Pharmacological Society.
FAU - Clark, Richard V
AU  - Clark RV
AD  - Muscle Metabolism Discovery Performance Unit, GlaxoSmithKline, Research Triangle 
      Park, NC, USA.
FAU - Walker, Ann C
AU  - Walker AC
AD  - Muscle Metabolism Discovery Performance Unit, GlaxoSmithKline, Research Triangle 
      Park, NC, USA.
FAU - Andrews, Susan
AU  - Andrews S
AD  - Muscle Metabolism Discovery Performance Unit, GlaxoSmithKline, Research Triangle 
      Park, NC, USA.
FAU - Turnbull, Philip
AU  - Turnbull P
AD  - Receptos, a wholly owned Subsidiary of Celgene, San Diego, CA, USA.
FAU - Wald, Jeffrey A
AU  - Wald JA
AD  - qPharmetra, LLC, Cary, NC, USA.
FAU - Magee, Mindy H
AU  - Magee MH
AD  - Clinical Pharmacology Modeling and Simulation, GlaxoSmithKline, King of Prussia, 
      PA, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170610
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (AR protein, human)
RN  - 0 (Anabolic Agents)
RN  - 0 (Indoles)
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Placebos)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Sex Hormone-Binding Globulin)
RN  - 47M5ZXU844 (GSK2881078)
SB  - IM
CIN - Br J Clin Pharmacol. 2017 Oct;83(10):2131-2133. PMID: 28621446
CIN - Br J Clin Pharmacol. 2017 Dec;83(12 ):2599-2601. PMID: 28755533
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Anabolic Agents/adverse effects/pharmacokinetics/*pharmacology
MH  - Cross-Over Studies
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Electrocardiography
MH  - Female
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Heart/drug effects
MH  - Humans
MH  - Indoles/adverse effects/pharmacokinetics/*pharmacology
MH  - Lipoproteins, HDL/blood
MH  - Male
MH  - Middle Aged
MH  - Muscle Strength/*drug effects
MH  - Placebos
MH  - Postmenopause
MH  - Receptors, Androgen/*metabolism
MH  - Sex Factors
MH  - Sex Hormone-Binding Globulin/analysis
MH  - Young Adult
PMC - PMC5595940
OTO - NOTNLM
OT  - biomarkers
OT  - drug development
OT  - pharmacodynamics
OT  - pharmacokinetics
EDAT- 2017/04/28 06:00
MHDA- 2018/06/05 06:00
PMCR- 2018/10/01
CRDT- 2017/04/28 06:00
PHST- 2016/09/22 00:00 [received]
PHST- 2017/03/10 00:00 [revised]
PHST- 2017/04/04 00:00 [accepted]
PHST- 2017/04/28 06:00 [pubmed]
PHST- 2018/06/05 06:00 [medline]
PHST- 2017/04/28 06:00 [entrez]
PHST- 2018/10/01 00:00 [pmc-release]
AID - BCP13316 [pii]
AID - 10.1111/bcp.13316 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2017 Oct;83(10):2179-2194. doi: 10.1111/bcp.13316. Epub 2017 
      Jun 10.