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Pharmacokinetics, Pharmacodynamics, and Safety of a Long‐Acting Human Growth Hormone (MOD‐4023) in Healthy Japanese and Caucasian Adults
Author(s) -
Kramer William G.,
JaronMendelson Michal,
Koren Ronit,
Hershkovitz Oren,
Hart Gili
Publication year - 2017
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.414
Subject(s) - medicine , pharmacodynamics , pharmacokinetics , pharmacology , mod , growth hormone , hormone , artificial intelligence , computer science
Daily injections of growth hormone (GH) as replacement therapy in GH‐deficient (GHD) patients may cause poor compliance and inconvenience. C‐terminal peptide–modified human GH (MOD4023) has been developed for onceweekly administration in GHD adults and children. In the present study, the pharmacokinetics (PK) and pharmacodynamics (PD) of a single subcutaneous dose of MOD4023 were evaluated in healthy Caucasian and Japanese adults, using a phase 1 double‐blind, vehicle‐controlled, randomized study design. The study was conducted in 42 healthy Japanese (n = 21) and Caucasian (n = 21) men receiving either MOD‐4023 at a dose of 2.5, 7.5, or 15 mg or vehicle. In the 2.5‐ and 7.5‐mg cohorts, no differences in mean MOD‐4023 serum concentration were found between Japanese and Caucasian subjects. A comparison of PK parameters in the 15‐mg group suggests a slower absorption rate of MOD‐4023 in Japanese subjects. PD analysis showed no apparent differences in IGF‐1 and IGFBP‐3 plasma concentrations between the Japanese and Caucasian subjects and indicated that a dose of 15 mg achieved the maximal effect in both ethnic groups. MOD‐4023 demonstrated a favorable safety profile and local tolerance following single‐dose subcutaneous administration. This study provides additional support for the development of MOD‐4023 as a long‐acting human growth hormone formulation for once‐weekly administration.