Assessment of the Pharmacokinetics, Pharmacodynamics, and Safety of Single Doses of TV-1106, a Long-Acting Growth Hormone, in Healthy Japanese and Caucasian Subjects.

Clin Pharmacol Drug Dev 2017 Jul 21;6(4):331-342. Epub 2016 Sep 21.

Teva Pharmaceuticals, Inc., Netanya, Israel.

TV-1106 is a human serum albumin genetically fused to recombinant human growth hormone, designed to provide a long-acting alternative to daily growth hormone (GH) injections in patients with GH deficiency. This study investigated the pharmacokinetics, pharmacodynamics, and safety of single subcutaneous doses of TV-1106 (7.5, 15, 50, and 100 mg) in Japanese (n = 44) and caucasian (n = 44) healthy subjects. TV-1106 pharmacokinetics and pharmacodynamics were comparable in Japanese and caucasian populations. TV-1106 demonstrated relatively slow absorption (median t , 10-30 hours) and a mean elimination half-life of 26-36 hours. Apparent clearance and volume of distribution decreased with increasing TV-1106 doses in both populations and appeared to increase more than dose proportionality across the tested doses. Insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) increased in a dose-related manner, with maximum responses observed at 33-96 and 42-109 hours, respectively. IGF-1 and IGFBP-3 returned to baseline values at 168 hours following 7.5 and 15 mg of TV-1106, and 336 hours following 50 and 100 mg of TV-1106. TV-1106 appeared safe in both populations. There was no evidence of differences in pharmacokinetics, pharmacodynamics, or safety of TV-1106 between Japanese and caucasian populations. The data also demonstrate long-acting growth hormone properties of TV-1106 and support its potential for once-weekly dosing.

Download full-text PDF

Source
http://dx.doi.org/10.1002/cpdd.294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516185PMC
July 2017
12 Reads

Publication Analysis

Top Keywords

pharmacokinetics pharmacodynamics
16
growth hormone
16
japanese caucasian
16
pharmacodynamics safety
12
tv-1106
11
caucasian populations
8
long-acting growth
8
doses tv-1106
8
safety single
8
subjects tv-1106
8
hours
5
growth
5
tv-1106 appeared
4
hours apparent
4
26-36 hours
4
appeared safe
4
clearance volume
4
apparent clearance
4
volume distribution
4
decreased increasing
4

References

(Supplied by CrossRef)
Adherence to medication
Osterberg et al.
N Engl J Med 2005
Status of long-acting-growth hormone preparations - 2015
Høybye et al.
Growth Horm IGF Res 2015

Similar Publications