title: Assessment of the Pharmacokinetics, Pharmacodynamics, and Safety of Single Doses of TV-1106, a Long-Acting Growth Hormone, in Healthy Japanese and Caucasian Subjects.
abstract: 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 tmax, 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.
authors.affiliation: Teva Pharmaceuticals, Inc., Netanya, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Cohen-Barak
authors.affiliation: Teva Pharmaceuticals, Inc., Netanya, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Barkay
authors.affiliation: Teva Pharmaceuticals, Inc., West Chester, PA, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Rasamoelisolo
authors.affiliation: Teva Pharmaceuticals Inc., Frazer, PA, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Butler
authors.affiliation: Teva Pharmaceutical K.K., Tokyo, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Teva Pharmaceuticals, Inc., Netanya, Israel.
authors.forename: Merav
authors.initials: M
authors.lastname: Bassan
authors.affiliation: Parexel Early Phase Clinical Unit, Los Angeles, CA, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Yoon
authors.affiliation: Teva Pharmaceuticals, Inc., Netanya, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Spiegelstein
mesh_terms: D000328:Adult; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D005260:Female; D064368:Healthy Volunteers; D019382:Human Growth Hormone / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007279:Injections, Subcutaneous; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000075462:Serum Albumin, Human / Q000235:genetics* / Q000378:metabolism; D044465:White People; D055815:Young Adult
chemical_list: C583557:IGF1 protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D011993:Recombinant Fusion Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D000075462:Serum Albumin, Human
keywords: Japanese; TV-1106; growth hormone deficiency (GHD); insulin-like growth factor (IGF-1); weekly hGH