title: The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men.
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.
authors.affiliation: Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Shehzad
authors.initials: S
authors.lastname: Basaria
authors.forename: Lauren
authors.initials: L
authors.lastname: Collins
authors.forename: E Lichar
authors.initials: EL
authors.lastname: Dillon
authors.forename: Katie
authors.initials: K
authors.lastname: Orwoll
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Storer
authors.forename: Renee
authors.initials: R
authors.lastname: Miciek
authors.forename: Jagadish
authors.initials: J
authors.lastname: Ulloor
authors.forename: Anqi
authors.initials: A
authors.lastname: Zhang
authors.forename: Richard
authors.initials: R
authors.lastname: Eder
authors.forename: Heather
authors.initials: H
authors.lastname: Zientek
authors.forename: Gilad
authors.initials: G
authors.lastname: Gordon
authors.forename: Syed
authors.initials: S
authors.lastname: Kazmi
authors.forename: Melinda
authors.initials: M
authors.lastname: Sheffield-Moore
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000728:Androgens / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004311:Double-Blind Method; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis; D053580:Muscle Strength / Q000187:drug effects; D009928:Organ Specificity; D011467:Prostate / Q000187:drug effects; D011944:Receptors, Androgen / Q000187:drug effects*; D013739:Testosterone / Q000097:blood; D055815:Young Adult
chemical_list: C410798:AR protein, human; D000728:Androgens; D012739:Gonadal Steroid Hormones; D008055:Lipids; D009124:Muscle Proteins; D011944:Receptors, Androgen; D013739:Testosterone