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.

Assessment of In Vitro Bioaccessibility and In Vivo Oral Bioavailability as Complementary Tools to Better Understand the Effect of Cooking on Methylmercury, Arsenic, and Selenium in Tuna

“…In the case of negative Crbc, where Cserum > Cwb, Crbc was set to zero. Kinetic assessment was done using the serum concentration-time profile and exploiting the following pharmacokinetic parameters: peak concentration (C max ) and time to peak concentration (T max ) were used as indirect metrics to characterize the rate of absorption, whereas the systemic exposure was assessed through dose-normalized area-under-thecurve from 0 to 540 min post-meal (AUC 0-540 ), from the linear trapezoidal method [54][55][56].…”

Adult growth hormone deficiency: clinical advances and approaches to improve adherence

“…Following the publication of the study by Lippe et al [176] in 1979 using a depot GH preparation in gelatin solution, the next LAGH preparation that was developed was somatropin (rDNA origin), which was micronized zinc-stabilized GH encapsulated in microspheres (Nutropin Depot). Since then, other LAGH preparations have been developed and evaluated, namely LB03002 [177][178][179][180][181][182][183][184], Jintrolong [185,186], Somapacitan (NNC0195-0092) [187,188], ARX201, NNC126-0083 [189][190][191][192], PHA-794428 [193,194], Somavaratan (VRS-317) [195,196], TV-1106 [197,198], ALTU-238, TransCon GH (ACP-001) [199][200][201][202], GX-H9 [203], LAPSrhGH/HM10560A, MOD-4023 [204][205][206][207][208], CP016, BBT-031, ProFuse GH, and AG-B1512, with phase 2 and 3 studies that primarily assessed longitudinal growth in children and changes in body composition in adults as main primary endpoints [178,179,182,186,195,209,210].…”