A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia

J Nutr Health Aging. 2013;17(6):533-43. doi: 10.1007/s12603-013-0335-x.

Abstract

Background: Sarcopenia, the age-related loss of muscle mass [defined as appendicular LBM/Height2 (aLBM/ht2) below peak value by>1SD], strength and function, is a major contributing factor to frailty in the elderly. MK-0773 is a selective androgen receptor modulator designed to improve muscle function while minimizing effects on other tissues.

Objectives: The primary objective of this study was to demonstrate an improvement in muscle strength and lean body mass (LBM) in sarcopenic frail elderly women treated with MK-0773 relative to placebo.

Design: This was a randomized, double-blind, parallel-arm, placebo-controlled, multicenter, 6-month study. Participants were randomized in a 1:1 ratio to receive either MK-0773 50mg b.i.d. or placebo; all participants received Vitamin D and protein supplementation.

Setting: General community.

Participants: 170 Women aged ≥65 with sarcopenia and moderate physical dysfunction.

Measurements: Dual energy X-ray absorptiometry, muscle strength and power, physical performance measures.

Results: Participants receiving MK-0773 showed a statistically significant increase in LBM from baseline at Month 6 vs. placebo (p<0.001). Participants receiving both MK-0773 and placebo showed a statistically significant increase in strength from baseline to Month 6, but the mean difference between the two groups was not significant (p=0.269). Both groups showed significant improvement from baseline at Month 6 in physical performance measures, but there were no statistically significant differences between participants receiving MK-0773 and placebo. A greater number of participants experienced elevated transaminases in the MK-0773 group vs. placebo, which resolved after discontinuation of study therapy. MK-0773 was generally well-tolerated with no evidence of androgenization.

Conclusions: The MK-0773-induced increase in LBM did not translate to improvement in strength or function vs. placebo. The improvement of strength and physical function in the placebo group could be at least partly attributed to protein and vitamin D supplementation.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Aged
  • Aged, 80 and over
  • Azasteroids / administration & dosage*
  • Body Composition / drug effects
  • Dietary Proteins / administration & dosage
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Frail Elderly
  • Humans
  • Muscle Strength / drug effects
  • Muscle, Skeletal / drug effects*
  • Musculoskeletal Physiological Phenomena / drug effects
  • Receptors, Androgen / drug effects
  • Sarcopenia / drug therapy*
  • Sarcopenia / physiopathology
  • Vitamin D / administration & dosage

Substances

  • 3-fluoro-N-(3H-imidazo(4,5-b)pyridin-2-ylmethyl)-1,4a,6a-trimethyl-2-oxo-2,4a,4b,5,6,6a,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-indeno(5,4-f)quinoline-7-carboxamide
  • AR protein, human
  • Azasteroids
  • Dietary Proteins
  • Receptors, Androgen
  • Vitamin D