The pharmacokinetics, pharmacodynamics, safety and tolerability of a single dose of NN703, a novel orally active growth hormone secretagogue in healthy male volunteers

The aim of the present study was to investigate the pharmacodynamics, pharm acokinetics, safety and tolerability of a single dose of NN703 (tabimorelin ), a growth hormone secretagogue in healthy male subjects. The study design was double blind, randomized and placebo-controlled, with eight escalating dose levels (0.05-12 mg/kg bodyweight (BW)). NN703 was well tolerated by t he subjects. The GH area under the curve (AUC) (0-24 h) was significantly h igher when compared to placebo for the three highest dose levels (3.0 mg/kg : P = 0.027, 6.0 mg/kg: P = 0.0023, 12 mg/kg: P < 0.0001), and for GH maxim al concentration C-max the four highest dose levels were also significantly higher when compared to placebo (1.5 mg/kg: P = 0.04, 3.0 mg/kg: P = 0.014 3, 6.0 mg/kg: P = 0.0053, 12 mg/kg: P = 0.0007). Furthermore, there was a s ignificant increase in IGF-1 levels when compared to placebo for the 6.0 an d 12.0 mg/kg BW dose levels (P < 0.0001). Statistical analysis comparing th e AUC (0-24 h) of the NN703 (four highest dose levels) and placebo-treated groups showed no significant increases following NN703 for ACTH, LH, FSH, T SH, prolactin, and cortisol, however, subtle individual changes were noted in ACTH, cortisol and prolactin at doses above 3.0 mg/kg. In conclusion, NN 703 is a promising potential candidate for treatment of GH deficiency/insuf ficiency. (C) 2000 Harcourt Publishers Ltd.