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

J Gerontol A Biol Sci Med Sci. 2013 Jan;68(1):87-95. doi: 10.1093/gerona/gls078. Epub 2012 Mar 28.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Androgens / administration & dosage
  • Androgens / adverse effects
  • Androgens / pharmacokinetics*
  • Androgens / pharmacology*
  • Body Composition / drug effects
  • Body Weight / drug effects
  • Double-Blind Method
  • Gonadal Steroid Hormones / blood
  • Humans
  • Lipids / blood
  • Male
  • Middle Aged
  • Muscle Proteins / biosynthesis
  • Muscle Strength / drug effects
  • Organ Specificity
  • Prostate / drug effects
  • Receptors, Androgen / drug effects*
  • Testosterone / blood
  • Young Adult

Substances

  • AR protein, human
  • Androgens
  • Gonadal Steroid Hormones
  • Lipids
  • Muscle Proteins
  • Receptors, Androgen
  • Testosterone