Safety, pharmacokinetic and pharmacodynamic properties of TV-1106, a long-acting GH treatment for GH deficiency

Eur J Endocrinol. 2015 Nov;173(5):541-51. doi: 10.1530/EJE-15-0554. Epub 2015 Aug 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Healthy Volunteers
  • Human Growth Hormone* / administration & dosage
  • Human Growth Hormone* / adverse effects
  • Human Growth Hormone* / deficiency
  • Human Growth Hormone* / pharmacokinetics
  • Humans
  • Male
  • Recombinant Proteins / administration & dosage
  • Serum Albumin / administration & dosage
  • Young Adult

Substances

  • Recombinant Proteins
  • Serum Albumin
  • Human Growth Hormone