MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study

Arch Gerontol Geriatr. Sep-Oct 2011;53(2):183-9. doi: 10.1016/j.archger.2010.10.004. Epub 2010 Nov 9.

Abstract

Most elderly patients admitted for hip fracture suffer functional decline. Previous studies with MK-0677 in hip fracture patients suggested possible benefits to functional recovery. This is a randomized, double-blind study of 123 elderly hip fracture patients assigned to receive 25mg/day of MK-0677 (n = 62) or placebo (n = 61). Primary outcomes were a rank analysis of change during the study in objective functional performance measurements and insulin-like growth factor-1 (IGF-1) levels in blood. At 24-weeks, the mean stair climbing power increased by 12.5 W in the MK-0677 group (95% confidence interval (CI) = -10.95-35.88; p = 0.292) compared with placebo. Gait speed increased by a 0.7-score difference in the means (95% CI = 0.17-1.28; p = 0.011). There was no improvement in MK-0677 treated patients in several other functional performance measures. The MK-0677 group experienced fewer falls during the study compared to placebo and smaller number of patients who had any falls (p = 0.096). Levels of IGF-1 in treated patients increased by 51.4 ng/ml (95% CI = 34.42-68.44; p < 0.001) compared to placebo. Trial was terminated early due to a safety signal of congestive heart failure in a limited number of patients. In hip fracture patients treated with 25mg/day MK-0677, the increase in plasma IGF-1 levels was not paralleled by improvement in most functional performance measures. MK-0677 has an unfavorable safety profile in this patient population.

Trial registration: ClinicalTrials.gov NCT00128115.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Fracture Healing / physiology*
  • Hip Fractures / drug therapy*
  • Hip Fractures / physiopathology
  • Hip Fractures / rehabilitation
  • Humans
  • Indoles / administration & dosage
  • Indoles / therapeutic use*
  • Lower Extremity / physiology*
  • Male
  • Middle Aged
  • Muscle Strength / physiology*
  • Physical Therapy Modalities
  • Prospective Studies
  • Range of Motion, Articular / physiology*
  • Recovery of Function*
  • Spiro Compounds / administration & dosage
  • Spiro Compounds / therapeutic use*
  • Treatment Outcome

Substances

  • Indoles
  • Spiro Compounds
  • ibutamoren mesylate

Associated data

  • ClinicalTrials.gov/NCT00128115