PMID- 26286586
OWN - NLM
STAT- MEDLINE
DCOM- 20160112
LR  - 20190126
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Print)
IS  - 0804-4643 (Linking)
VI  - 173
IP  - 5
DP  - 2015 Nov
TI  - Safety, pharmacokinetic and pharmacodynamic properties of TV-1106, a long-acting 
      GH treatment for GH deficiency.
PG  - 541-51
LID - 10.1530/EJE-15-0554 [doi]
AB  - BACKGROUND: TV-1106 (Teva Pharmaceuticals) is a genetically fused recombinant 
      protein of human GH (hGH) and human serum albumin, in development for treatment 
      of GH deficiency (GHD). TV-1106 is expected to have an extended duration of 
      action compared to daily GH treatment and may enable a reduction in the frequency 
      of injections and improve compliance and quality of life for adults and children 
      requiring GHD therapy. OBJECTIVE: To assess the safety, local tolerability, 
      pharmacokinetics and pharmacodynamics of TV-1106 following single s.c. injections 
      in healthy male volunteers. METHODS: Subjects (n=56) were assigned to one of 
      seven ascending dose groups (3-100 mg) and received either a single dose of 
      TV-1106 (n=6) or placebo (n=2) by s.c. injection. RESULTS: Eighteen subjects 
      reported 43 adverse effects (AEs), which were mild to moderate; no serious AEs 
      (SAEs) occurred. In 50, 70 and 100 mg groups there were mild to moderate 
      increases in heart rate and systolic blood pressure that significantly correlated 
      with higher levels of IGF1. TV-1106 showed pharmacokinetic characteristics of a 
      long-acting hGH as demonstrated by a terminal elimination half-life of 23-35 h, 
      delayed time of peak concentration, and systemic levels seen up to 7 days after 
      dosing. IGF1 levels increased in a dose-dependent manner, before reaching a 
      plateau, with levels above baseline extending beyond 7 days post dose. 
      CONCLUSION: Single administration of TV-1106 up to 100 mg was safe in healthy 
      volunteers. Pharmacokinetics and pharmacodynamics support once-weekly 
      administration in patients with GHD.
CI  - (c) 2015 The authors.
FAU - Cohen-Barak, Orit
AU  - Cohen-Barak O
AD  - Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva 
      Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, 
      Pennsylvania, USACardiac Safety Consultants LtdLondon, UK 
      orit.cohen-barak@teva.co.il.
FAU - Sakov, Anat
AU  - Sakov A
AD  - Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva 
      Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, 
      Pennsylvania, USACardiac Safety Consultants LtdLondon, UK.
FAU - Rasamoelisolo, Michele
AU  - Rasamoelisolo M
AD  - Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva 
      Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, 
      Pennsylvania, USACardiac Safety Consultants LtdLondon, UK.
FAU - Bassan, Merav
AU  - Bassan M
AD  - Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva 
      Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, 
      Pennsylvania, USACardiac Safety Consultants LtdLondon, UK.
FAU - Brown, Kurt
AU  - Brown K
AD  - Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva 
      Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, 
      Pennsylvania, USACardiac Safety Consultants LtdLondon, UK.
FAU - Mendzelevski, Boaz
AU  - Mendzelevski B
AD  - Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva 
      Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, 
      Pennsylvania, USACardiac Safety Consultants LtdLondon, UK.
FAU - Spiegelstein, Ofer
AU  - Spiegelstein O
AD  - Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva 
      Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, 
      Pennsylvania, USACardiac Safety Consultants LtdLondon, UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150818
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (Recombinant Proteins)
RN  - 0 (Serum Albumin)
RN  - 12629-01-5 (Human Growth Hormone)
SB  - IM
MH  - Adult
MH  - Healthy Volunteers
MH  - *Human Growth Hormone/administration & dosage/adverse 
      effects/deficiency/pharmacokinetics
MH  - Humans
MH  - Male
MH  - Recombinant Proteins/administration & dosage
MH  - Serum Albumin/administration & dosage
MH  - Young Adult
PMC - PMC4584421
EDAT- 2015/08/20 06:00
MHDA- 2016/01/13 06:00
PMCR- 2015/11/01
CRDT- 2015/08/20 06:00
PHST- 2015/06/04 00:00 [received]
PHST- 2015/08/18 00:00 [accepted]
PHST- 2015/08/20 06:00 [entrez]
PHST- 2015/08/20 06:00 [pubmed]
PHST- 2016/01/13 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - EJE-15-0554 [pii]
AID - EJE150554 [pii]
AID - 10.1530/EJE-15-0554 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2015 Nov;173(5):541-51. doi: 10.1530/EJE-15-0554. Epub 2015 Aug 
      18.