The pharmacokinetics, pharmacodynamics, safety and tolerability following 7 days daily oral treatment with NN703 in healthy male subjects

The aim of the present study was to assess the safety, pharmacokinetics and pharmacodynamics (including specificity) of NN703 (tabimorelin), a growth hormone (GH) secretagogue, in healthy male subjects following treatment for 7 days once-daily. This was a randomized, double-blind and placebo-control led study with four active dose levels: 1.71, 3.0, 4.5 and 6.86 mg/kg body weight. There was a dose-related increase for GH area under the curve (AUC) (0-12 h) and GH C-max (0-12 h); these were significantly higher on both da ys 1 and 7 as compared with placebo treatment (P= 0.04 to P < 0.0001); howe ver, an overall significant decrease in GH release was found from day 1 to day 7 (P < 0.001). Insulin-like growth factor-I (IGF-I) and IGF binding pro tein 3 (IGFBP-3) increased at all dose levels (including placebo); however, a significantly higher increase as compared with placebo treatment was obs erved at the three highest dose levels for IGF-I (P = 0.04-0.0006) and at t he highest dose level for IGFBP-3 (P = 0.03). There was no statistically si gnificant increase in AUC (0-5 h) for follicle-stimulating hormone, luteini zing hormone and cortisol between active and placebo treatment for day 1 or 7. On day 1 only, a statistically significant increase in AUC (0-5 h) was found for prolactin at 1.71 and 6.86 mg/kg (P < 0.05), for thyroid-stimulat ing hormone (TSH) at 3.0 mg/kg (P < 0.01) and for adrenocorticotrophic horm one (ACTH) at 4.5 mg/kg (P < 0.05); however, no dose-response relationship was observed for TSH or ACTH. In addition, a statistically significant decr ease in AUC (0-5 h) for ACTH (3.0 and 6.86 mg/kg) and cortisol (1.71 mg/kg) was observed on day 7 (P < 0.05). Thus, NN703 is a promising candidate for treatment of absolute or relative GH deficiency. (C) 2001 Harcourt Publish ers Ltd.