BACKGROUND: Cachexia, also known as muscle wasting, is a complex metabolic condition characterized by loss of skeletal muscle and a decline in physical function. Muscle wasting is associated with cancer, sarcopenia, chronic obstructive pulmonary disease, end-stage renal disease, and other chronic conditions and results in significant morbidity and mortality. GTx-024 (enobosarm) is a nonsteroidal selective androgen receptor modulator (SARM) that has tissue-selective anabolic effects in muscle and bone, while sparing other androgenic tissue related to hair growth in women and prostate effects in men. GTx-024 has demonstrated promising pharmacologic effects in preclinical studies and favorable safety and pharmacokinetic profiles in phase I investigation. METHODS: A 12-week double-blind, placebo-controlled phase II clinical trial was conducted to evaluate GTx-024 in 120 healthy elderly men (>60 years of age) and postmenopausal women. The primary endpoint was total lean body mass assessed by dual energy X-ray absorptiometry, and secondary endpoints included physical function, body weight, insulin resistance, and safety. RESULTS: GTx-024 treatment resulted in dose-dependent increases in total lean body mass that were statistically significant (P < 0.001, 3 mg vs. placebo) and clinically meaningful. There were also significant improvements in physical function (P = 0.013, 3 mg vs. placebo) and insulin resistance (P = 0.013, 3 mg vs. placebo). The incidence of adverse events was similar between treatment groups. CONCLUSION: GTx-024 showed a dose-dependent improvement in total lean body mass and physical function and was well tolerated. GTx-024 may be useful in the prevention and/or treatment of muscle wasting associated with cancer and other chronic diseases.
RCT Entities:
BACKGROUND:Cachexia, also known as muscle wasting, is a complex metabolic condition characterized by loss of skeletal muscle and a decline in physical function. Muscle wasting is associated with cancer, sarcopenia, chronic obstructive pulmonary disease, end-stage renal disease, and other chronic conditions and results in significant morbidity and mortality. GTx-024 (enobosarm) is a nonsteroidal selective androgen receptor modulator (SARM) that has tissue-selective anabolic effects in muscle and bone, while sparing other androgenic tissue related to hair growth in women and prostate effects in men. GTx-024 has demonstrated promising pharmacologic effects in preclinical studies and favorable safety and pharmacokinetic profiles in phase I investigation. METHODS: A 12-week double-blind, placebo-controlled phase II clinical trial was conducted to evaluate GTx-024 in 120 healthy elderly men (>60 years of age) and postmenopausal women. The primary endpoint was total lean body mass assessed by dual energy X-ray absorptiometry, and secondary endpoints included physical function, body weight, insulin resistance, and safety. RESULTS:GTx-024 treatment resulted in dose-dependent increases in total lean body mass that were statistically significant (P < 0.001, 3 mg vs. placebo) and clinically meaningful. There were also significant improvements in physical function (P = 0.013, 3 mg vs. placebo) and insulin resistance (P = 0.013, 3 mg vs. placebo). The incidence of adverse events was similar between treatment groups. CONCLUSION:GTx-024 showed a dose-dependent improvement in total lean body mass and physical function and was well tolerated. GTx-024 may be useful in the prevention and/or treatment of muscle wasting associated with cancer and other chronic diseases.
Authors: Shehzad Basaria; Andrea D Coviello; Thomas G Travison; Thomas W Storer; Wildon R Farwell; Alan M Jette; Richard Eder; Sharon Tennstedt; Jagadish Ulloor; Anqi Zhang; Karen Choong; Kishore M Lakshman; Norman A Mazer; Renee Miciek; Joanne Krasnoff; Ayan Elmi; Philip E Knapp; Brad Brooks; Erica Appleman; Sheetal Aggarwal; Geeta Bhasin; Leif Hede-Brierley; Ashmeet Bhatia; Lauren Collins; Nathan LeBrasseur; Louis D Fiore; Shalender Bhasin Journal: N Engl J Med Date: 2010-06-30 Impact factor: 91.245
Authors: Jiyun Chen; Dong Jin Hwang; Kiwon Chung; Casey E Bohl; Scott J Fisher; Duane D Miller; James T Dalton Journal: Endocrinology Date: 2005-09-15 Impact factor: 4.736
Authors: Virginia A Hughes; Walter R Frontera; Ronenn Roubenoff; William J Evans; Maria A Fiatarone Singh Journal: Am J Clin Nutr Date: 2002-08 Impact factor: 7.045
Authors: Stephan von Haehling; John E Morley; Andrew J S Coats; Stefan D Anker Journal: J Cachexia Sarcopenia Muscle Date: 2010-10-26 Impact factor: 12.910
Authors: Zachary J Solomon; Jorge Rivera Mirabal; Daniel J Mazur; Taylor P Kohn; Larry I Lipshultz; Alexander W Pastuszak Journal: Sex Med Rev Date: 2018-11-30
Authors: Kornelia J Skowron; Kenneth Booker; Changfeng Cheng; Simone Creed; Brian P David; Phillip R Lazzara; Amy Lian; Zamia Siddiqui; Thomas E Speltz; Terry W Moore Journal: Mol Cell Endocrinol Date: 2019-06-01 Impact factor: 4.102
Authors: Ann Zenobia Moore; Giorgio Caturegli; E Jeffrey Metter; Sokratis Makrogiannis; Susan M Resnick; Tamara B Harris; Luigi Ferrucci Journal: J Am Geriatr Soc Date: 2014-01-17 Impact factor: 5.562
Authors: Adrian S Dobs; Ralph V Boccia; Christopher C Croot; Nashat Y Gabrail; James T Dalton; Michael L Hancock; Mary A Johnston; Mitchell S Steiner Journal: Lancet Oncol Date: 2013-03-14 Impact factor: 41.316