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

• Published in: Growth hormone & IGF research Vol. 11; no. 1; pp. 41 - 48
• Main Authors: Zdravkovic, M., Christiansen, T., Eliot, L., Agersoe, H., Thomsen, M.S., Falch, J.F., Søgaard, B., Ynddal, L., Ilondo, M.M.
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.02.2001
• Subjects: Administration, Oral; Adrenocorticotropic Hormone - metabolism; Adult; Area Under Curve; Body Weight; Dipeptides - administration & dosage; Dipeptides - pharmacokinetics; Dipeptides - toxicity; Dose-Response Relationship, Drug; Double-Blind Method; Follicle Stimulating Hormone - metabolism; Humans; Hydrocortisone - metabolism; Luteinizing Hormone - metabolism; Male; NN703, growth hormone secretagogue, clinical study, tabimorelin; Placebos; Thyrotropin - metabolism; Time Factors; NN703, growth hormone secretagogue, clinical study, tabimorelin
• ISSN: 1096-6374; 1532-2238
• DOI: 10.1054/ghir.2000.0188

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-controlled 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 GHCmax (0–12 h); these were significantly higher on both days 1 and 7 as compared with placebo treatment (P = 0.04 to P< 0.0001); however, 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 protein 3 (IGFBP-3) increased at all dose levels (including placebo); however, a significantly higher increase as compared with placebo treatment was observed at the three highest dose levels for IGF-I (P = 0.04–0.0006) and at the highest dose level for IGFBP-3 (P = 0.03). There was no statistically significant increase in AUC (0–5 h) for follicle-stimulating hormone, luteinizing 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-stimulating hormone (TSH) at 3.0 mg/kg (P< 0.01) and for adrenocorticotrophic hormone (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 decrease 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.