The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men

Shehzad Basaria, Lauren Collins, E. Lichar Dillon, Katie Orwoll, Thomas W. Storer, Renee Miciek, Jagadish Ulloor, Anqi Zhang, Richard Eder, Heather Zientek, Gilad Gordon, Syed Kazmi, Melinda Sheffield-Moore, Shalender Bhasin

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Background.Concerns about potential adverse effects of testosterone on prostate have motivated the development of selective androgen receptor modulators that display tissue-selective activation of androgenic signaling. LGD-4033, a novel nonsteroidal, oral selective androgen receptor modulator, binds androgen receptor with high affinity and selectivity.Objectives.To evaluate the safety, tolerability, pharmacokinetics, and effects of ascending doses of LGD-4033 administered daily for 21 days on lean body mass, muscle strength, stair-climbing power, and sex hormones.Methods.In this placebo-controlled study, 76 healthy men (21-50 years) were randomized to placebo or 0.1, 0.3, or 1.0 mg LGD-4033 daily for 21 days. Blood counts, chemistries, lipids, prostate-specific antigen, electrocardiogram, hormones, lean and fat mass, and muscle strength were measured during and for 5 weeks after intervention.Results.LGD-4033 was well tolerated. There were no drug-related serious adverse events. Frequency of adverse events was similar between active and placebo groups. Hemoglobin, prostate-specific antigen, aspartate aminotransferase, alanine aminotransferase, or QT intervals did not change significantly at any dose. LGD-4033 had a long elimination half-life and dose-proportional accumulation upon multiple dosing. LGD-4033 administration was associated with dose-dependent suppression of total testosterone, sex hormone-binding globulin, high density lipoprotein cholesterol, and triglyceride levels. follicle-stimulating hormone and free testosterone showed significant suppression at 1.0-mg dose only. Lean body mass increased dose dependently, but fat mass did not change significantly. Hormone levels and lipids returned to baseline after treatment discontinuation.Conclusions.LGD-4033 was safe, had favorable pharmacokinetic profile, and increased lean body mass even during this short period without change in prostate-specific antigen. Longer randomized trials should evaluate its efficacy in improving physical function and health outcomes in select populations.

Original languageEnglish (US)
Pages (from-to)87-95
Number of pages9
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume68
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • Cachexia
  • Function promoting anabolic therapies
  • SARMs
  • Sarcopenia
  • Selective androgen receptor modulators

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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    Basaria, S., Collins, L., Dillon, E. L., Orwoll, K., Storer, T. W., Miciek, R., Ulloor, J., Zhang, A., Eder, R., Zientek, H., Gordon, G., Kazmi, S., Sheffield-Moore, M., & Bhasin, S. (2013). The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 68(1), 87-95. https://doi.org/10.1093/gerona/gls078