Dahlke, Marion, Ng, Dik, Yamaguchi, Masayuki, Machineni, Surendra Kumar, Berger, Sergio, Canadi Semadeni, Jasna, Rajman, Iris, Lloyd, Pete and Pang, Yinuo (2015) Ethnic sensitivity study with serelaxin. 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 populat, 55 (4). pp. 415-422. ISSN 00912700

Abstract

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 AUCinf over the entire dose range. A significant increase in estimated glomerular filtration rate from baseline to Day 2 (30 μg/kg/day and 100 μg/kg/day) and to Day 3 (10 μg/kg/day 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.

Item Type:	Article
Keywords:	Serelaxin, PK, PD, safety, ethnic sensitivity
Date Deposited:	28 Apr 2016 23:45
Last Modified:	28 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/23456