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Safety and tolerability of serelaxin, a recombinant human relaxin‐2 in development for the treatment of acute heart failure, in healthy Japanese volunteers and a comparison of pharmacokinetics and pharmacodynamics in healthy Japanese and Caucasian populations
Author(s) -
Dahlke Marion,
Ng Dik,
Yamaguchi Masayuki,
Machineni Surendra,
Berger Sergej,
Canadi Jasna,
Rajman Iris,
Lloyd Peter,
Pang Yinuo
Publication year - 2015
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.433
Subject(s) - medicine , tolerability , pharmacokinetics , placebo , pharmacodynamics , dosing , adverse effect , anesthesia , alternative medicine , pathology
Serelaxin, a recombinant form of the human relaxin‐2 hormone, is currently under clinical investigation for treatment of acute heart failure. This double‐blind, placebo‐controlled, dose‐ranging study investigated the effect of Japanese ethnicity on the pharmacokinetics (PK), pharmacodynamics (PD), and safety and tolerability of serelaxin. Japanese healthy subjects (n = 32) received 10, 30, or 100 µg/kg/day of serelaxin, or placebo, administered as a 48‐hour intravenous infusion. A Caucasian cohort (n = 8) receiving 30 µg/kg/day open‐label serelaxin was included for comparison. In all subjects, serum serelaxin concentrations increased rapidly after the start of infusion, approached steady state as early as 4 hours, and declined rapidly upon treatment cessation. Serum exposure to serelaxin increased with increasing doses. Statistical dose proportionality was shown for AUC inf over the entire dose range. A significant increase in estimated glomerular filtration rate from baseline to Day 2 (30 and 100 µg/kg/day) and to Day 3 (10 and 100 µg/kg/day) was observed compared with placebo. Serelaxin was well tolerated by all subjects. In conclusion, PK, PD, and safety profiles of serelaxin were generally comparable between Japanese and Caucasian subjects, suggesting that no dose adjustment will be required in Japanese subjects during routine clinical use of this agent.