Multicenter, Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Serelaxin in Japanese Patients With Acute Heart Failure.
BACKGROUND
Serelaxin, a recombinant form of human relaxin-2, is in development for treating acute heart failure (AHF) and a Phase II study in Japanese AHF patients was conducted.


RESULTS
A randomized, double-blind, placebo-controlled study of serelaxin at 10 and 30 µg·kg(-1)·day(-1)continuous intravenous infusion for up to 48 h, added to standard care for Japanese AHF patients. Primary endpoints were adverse events (AEs) through Day 5, serious AEs (SAEs) through Day 14, and serelaxin pharmacokinetics. Secondary endpoints included changes in systolic blood pressure (SBP) and cardiorenal biomarkers. A total of 46 patients received the study drug and were followed for 60 days. The observed AE profile was comparable between the groups, with no AEs of concern. Dose-dependent increase in the serum concentration of serelaxin was observed across the 2 dose rates of serelaxin. A greater reduction in SBP was observed with serelaxin 30 µg·kg(-1)·day(-1)vs. placebo (-7.7 [-16.4, 1.0] mmHg). A greater reduction in NT-proBNP was noted with serelaxin (-50.8% and -54.9% for 10 and 30 µg·kg(-1)·day(-1), respectively at Day 2).


CONCLUSIONS
Serelaxin was well tolerated in this study with Japanese AHF patients, with no AEs of concern and favorable beneficial trends on efficacy. These findings support further evaluation of serelaxin 30 µg·kg(-1)·day(-1)in this patient population.
Cardiology and Intensive Care Unit, Nippon Medical School Musashi-Kosugi Hospital.
Naoki
N
Sato
Wataru
W
Takahashi
Atsushi
A
Hirayama
Masayoshi
M
Ajioka
Naoto
N
Takahashi
Kaoru
K
Okishige
XingLi
X
Wang
Akio
A
Maki
Hideki
H
Maruyama
Ursula
U
Ebinger
Masayuki
M
Yamaguchi
Yinuo
Y
Pang
Hiroki
H
Matsumoto
Masatoshi
M
Kawana
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000627:therapeutic use; D015897:Comorbidity; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004417:Dyspnea / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D012065:Relaxin / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D015415:Biomarkers; D002317:Cardiovascular Agents; D010446:Peptide Fragments; D011994:Recombinant Proteins; C109794:pro-brain natriuretic peptide (1-76); C577649:serelaxin protein, human; D020097:Natriuretic Peptide, Brain; D012065:Relaxin