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


CONCLUSIONS
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.
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.
Orit
O
Cohen-Barak
Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, Pennsylvania, USACardiac Safety Consultants LtdLondon, UK.
Anat
A
Sakov
Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, Pennsylvania, USACardiac Safety Consultants LtdLondon, UK.
Michele
M
Rasamoelisolo
Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, Pennsylvania, USACardiac Safety Consultants LtdLondon, UK.
Merav
M
Bassan
Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, Pennsylvania, USACardiac Safety Consultants LtdLondon, UK.
Kurt
K
Brown
Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, Pennsylvania, USACardiac Safety Consultants LtdLondon, UK.
Boaz
B
Mendzelevski
Teva Pharmaceuticals Inc.12 Hatrufa Street, Netanya 42504, IsraelTeva Biopharmaceuticals Inc.Rockville, Maryland, USATeva Pharmaceuticals Inc.Frazer, Pennsylvania, USACardiac Safety Consultants LtdLondon, UK.
Ofer
O
Spiegelstein
D000328:Adult; D064368:Healthy Volunteers; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000172:deficiency / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage; D012709:Serum Albumin / Q000008:administration & dosage; D055815:Young Adult
D011994:Recombinant Proteins; D012709:Serum Albumin; D019382:Human Growth Hormone