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, pharmacokinetics, 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 the subjects. The GH area under the curve (AUC) (0-24 h) was significantly higher 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 maximal 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 = 0.0143, 6.0 mg/kg: P = 0.0053, 12 mg/kg: P = 0.0007). Furthermore, there was a significant increase in IGF-1 levels when compared to placebo for the 6.0 and 12.0 mg/kg BW dose levels (P< 0. 0001). Statistical analysis comparing the 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, TSH, prolactin, and cortisol, however, subtle individual changes were noted in ACTH, cortisol and prolactin at doses above 3.0 mg/kg. In conclusion, NN703 is a promising potential candidate for treatment of GH deficiency/insufficiency.
Zdravkovic
M
M
Department of Clinical Pharmacology, Novo Nordisk A/S, 2800 Bagsvaerd, Denmark. mzd@novo.dk
Søgaard
B
B
Ynddal
L
L
Christiansen
T
T
Agersø
H
H
Thomsen
M S
MS
Falch
J E
JE
Ilondo
M M
MM
D000284:Administration, Oral; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D004151:Dipeptides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D011388:Prolactin / Q000097:blood; D012449:Safety
D004151:Dipeptides; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; C120631:tabimorelin; D006854:Hydrocortisone