PMID- 11437473
OWN - NLM
STAT- MEDLINE
DCOM- 20010816
LR  - 20131121
IS  - 1096-6374 (Print)
IS  - 1096-6374 (Linking)
VI  - 11
IP  - 1
DP  - 2001 Feb
TI  - The pharmacokinetics, pharmacodynamics, safety and tolerability following 7 days 
      daily oral treatment with NN703 in healthy male subjects.
PG  - 41-8
AB  - 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 GH 
      C(max)(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.
CI  - Copyright 2001 Harcourt Publishers Ltd.
FAU - Zdravkovic, M
AU  - Zdravkovic M
AD  - Department of Clinical Pharmacology, Novo Nordisk A/S, 2880 Bagsvaerd, Denmark. 
      mzd@novonordisk.com
FAU - Christiansen, T
AU  - Christiansen T
FAU - Eliot, L
AU  - Eliot L
FAU - Agersoe, H
AU  - Agersoe H
FAU - Thomsen, M S
AU  - Thomsen MS
FAU - Falch, J F
AU  - Falch JF
FAU - Sogaard, B
AU  - Sogaard B
FAU - Ynddal, L
AU  - Ynddal L
FAU - Ilondo, M M
AU  - Ilondo MM
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - Scotland
TA  - Growth Horm IGF Res
JT  - Growth hormone & IGF research : official journal of the Growth Hormone Research 
      Society and the International IGF Research Society
JID - 9814320
RN  - 0 (Dipeptides)
RN  - 0 (Placebos)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - 9002-71-5 (Thyrotropin)
RN  - L51CBE03KF (tabimorelin)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Administration, Oral
MH  - Adrenocorticotropic Hormone/metabolism
MH  - Adult
MH  - Area Under Curve
MH  - Body Weight
MH  - Dipeptides/administration & dosage/*pharmacokinetics/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Follicle Stimulating Hormone/metabolism
MH  - Humans
MH  - Hydrocortisone/metabolism
MH  - Luteinizing Hormone/metabolism
MH  - Male
MH  - Placebos
MH  - Thyrotropin/metabolism
MH  - Time Factors
EDAT- 2001/07/05 10:00
MHDA- 2001/08/17 10:01
CRDT- 2001/07/05 10:00
PHST- 2001/07/05 10:00 [pubmed]
PHST- 2001/08/17 10:01 [medline]
PHST- 2001/07/05 10:00 [entrez]
AID - S1096-6374(00)90188-6 [pii]
AID - 10.1054/ghir.2000.0188 [doi]
PST - ppublish
SO  - Growth Horm IGF Res. 2001 Feb;11(1):41-8. doi: 10.1054/ghir.2000.0188.