title: Safety and PK/PD correlation of TV-1106, a recombinant fused human albumin-growth hormone, following repeat dose administration to monkeys.
abstract: TV-1106 is a recombinant human albumin genetically fused to growth hormone which is intended to reduce the frequency of injections for GH therapy users. We report the safety, tolerability, pharmacokinetics and pharmacodynamics of repeated subcutaneous injections of TV-1106 in Cynomolgus monkeys.
  
  
  
  Cynomolgus monkeys received four weekly subcutaneous injections of 0, 5, 10 or 20mg/kg TV-1106 and were monitored for safety signals throughout the study. Serum levels of TV-1106 and insulin-like growth factor 1 (IGF-1) were assayed.
  
  
  
  Treated animals showed no adverse effects or histopathological changes. TV-1106 serum concentrations showed sustained exposure to the drug. Exposure increased in a dose-dependent manner with peak concentrations at approximately 24h post-dosing and elimination half-lives in the range of 12 to 24h. IGF-1 serum concentrations were elevated throughout the entire study duration, indicative of the pharmacological response. There was a clear correlation between change in IGF-1 levels and dose or exposure to TV-1106.
  
  
  
  The safety, pharmacokinetic and pharmacodynamic findings support the further development of TV-1106 as a once-weekly administered treatment for patients with GHD.
authors.affiliation: Department of Non Clinical Safety, Teva Pharmaceutical Ltd, Netanya, Israel. Electronic address: Nurit.Ashkenazi01@teva.co.il.
authors.forename: Nurit
authors.initials: N
authors.lastname: Ashkenazi
authors.affiliation: Department of Non Clinical Safety, Teva Pharmaceutical Ltd, Netanya, Israel.
authors.forename: Moti
authors.initials: M
authors.lastname: Rosenstock
authors.affiliation: Department of Non Clinical Safety, Teva Pharmaceutical Ltd, Netanya, Israel.
authors.forename: Hussein
authors.initials: H
authors.lastname: Hallak
authors.affiliation: Department of Non Clinical Safety, Teva Pharmaceutical Ltd, Netanya, Israel.
authors.forename: Merav
authors.initials: M
authors.lastname: Bassan
authors.affiliation: Global Bioassays and Technology, Teva Biopharmaceuticals Rockville, United States.
authors.forename: Michele
authors.initials: M
authors.lastname: Rasamoelisolo
authors.affiliation: LPT Laboratory of Pharmacology and Toxicology GmbH & Co. KG, Germany.
authors.forename: Jost
authors.initials: J
authors.lastname: Leuschner
authors.affiliation: Department of Non Clinical Safety, Teva Pharmaceutical Ltd, Netanya, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Shinar
mesh_terms: D000818:Animals; D005260:Female; D019382:Human Growth Hormone / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000187:drug effects* / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D011994:Recombinant Proteins / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D000075462:Serum Albumin, Human / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D000075462:Serum Albumin, Human
keywords: GH; IGF-1; Long-acting; Monkey; Pharmacokinetics; Safety