| Reference | 1. Arch Gerontol Geriatr. 2011 Sep-Oct;53(2):183-9. doi:
10.1016/j.archger.2010.10.004. Epub 2010 Nov 9.
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MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip
fracture: a multicenter, randomized, placebo-controlled phase IIb study.
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Adunsky A(1), Chandler J, Heyden N, Lutkiewicz J, Scott BB, Berd Y, Liu N,
Papanicolaou DA.
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Author information: <br>
(1)Department of Geriatric Medicine, Sheba Medical Center, Tel Hashomer,
Ramat-Gan 52627 Israel. [email protected]
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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.
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2. Clin Pharmacol Ther. 2001 Jul;70(1):91-8.
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Effects of oral administration of ibutamoren mesylate, a nonpeptide growth
hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in
growth hormone-deficient children.
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Codner E(1), Cassorla F, Tiulpakov AN, Mericq MV, Avila A, Pescovitz OH, Svensson
J, Cerchio K, Krupa D, Gertz BJ, Murphy G.
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Author information: <br>
(1)Institute of Maternal and Child Research, University of Chile, Santiago,
Chile. [email protected]
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Ibutamoren mesylate (MK-0677), an orally active nonpeptide growth hormone (GH)
secretagogue, stimulates GH release through a pituitary and hypothalamic receptor
that is different from the GH-releasing hormone receptor. We evaluated the safety
and tolerability and the GH-insulin-like growth factor (IGF) responses to two
dosages of oral ibutamoren mesylate given to children with GH deficiency for 7 to
8 days. The patients, 18 prepubertal children (15 male, 3 female) with idiopathic
GH deficiency, had a chronologic age of 10.6 +/- 0.8 years (mean +/- SD), bone
age of 7.4 +/- 0.7 years, growth velocity < 10th percentile for age, height <
10th percentile for age, and a maximum GH response of < or = 10 microg/L to two
different GH stimulation tests. The children were assigned as follows to one of
three treatment groups with ibutamoren mesylate: 0.2 mg/kg per day for 7 days
(days 1-7 or 8-14) and matching placebo for the alternate 7 days (groups I and
II, respectively) or 0.8 mg/kg per day for 7 days (days 8-14, group III). On day
15 all patients received an 0.8-mg/kg dose of ibutamoren mesylate. Patients in
groups I and II were studied first to assess safety at the low dose before
advancement to the high dose. Hormonal profiles were evaluated on day -1
(baseline) and day 15, and the results were expressed as the change from baseline
within each group. After administration of ibutamoren mesylate 0.8 mg/kg for 8
days (group III), the median increases (on day 15) from baseline were as follows:
3.8 microg/L (range, 0 to 34.3) for serum GH peak concentration (P = .001), 4.3
microg x h/L (range, 1.3 to 35.6) for the GH area under the concentration-time
curve from time zero to 8 hours (AUC(0-8)) (P < .001), 12 microg/L (range, -4 to
116) for serum IGF-I (P = .01), and 0.4 microg/L (range, -0.9 to 1.5) for serum
IGF-binding protein 3 (IGFBP-3) (P = .01). There was no change in serum
prolactin, glucose, triiodothyronine, thyroxine, thyrotropin, peak serum
cortisol, and insulin concentrations or 24-hour urinary free cortisol after
administration of 0.8 mg/kg per day of ibutamoren mesylate for 8 days. We
conclude that short-term administration of ibutamoren mesylate can increase GH,
IGF-I, and IGFBP-3 levels in some children with GH deficiency. Thus this compound
is applicable for testing its effect on growth velocity.
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