Tadao Akizawa1, Masaomi Nangaku2, Takuhiro Yamaguchi3, Masanobu Arai4, Ryosuke Koretomo4, Kazuo Maeda4, Yuya Miyazawa4, Hideki Hirakata5. 1. Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan, akizawa@med.showa-u.ac.jp. 2. Division of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan. 3. Division of Biostatistics, Tohoku University Graduate School of Medicine, Miyagi, Japan. 4. Pharmaceutical Division, Japan Tobacco Inc., Tokyo, Japan. 5. Fukuoka Renal Clinic, Fukuoka, Japan.
Abstract
BACKGROUND:Enarodustat (JTZ-951) is an orally available hypoxia-inducible factor prolyl hydroxylase inhibitor that increases endogenous erythropoietin levels in the treatment of anemia associated with chronic kidney disease (CKD). OBJECTIVE: A phase 2b study of enarodustat to assess the hemoglobin (Hb) response, safety, and maintenance dosage was conducted in Japanese anemic patients with hemodialysis-dependent CKD. METHODS:Subjects receiving a stable dose of an erythropoiesis-stimulating agent were randomized to receive once-daily enarodustat at a dose of 2, 4, or 6 mg or placebo in a double-blind manner for 6 weeks (Period 1) followed by 24-week open treatment with enarodustat, adjusted in the range of 2-8 mg to maintain Hb within a target range (10.0-12.0 g/dL; Period 2). RESULTS: Change in Hb from baseline increased with enarodustat dose in Period 1. In Period 2, the proportion of subjects who maintained their Hb level within the target range at the end of treatment was 65.1%. To maintain Hb levels within the target range over the course of Period 2, approximately 80% of subjects required 2 dose adjustments or fewer. Enarodustat decreased hepcidin and ferritin levels, increased total iron-binding capacity, and was generally well tolerated. CONCLUSIONS: Enarodustat corrected and maintained Hb levels in anemic patients with hemodialysis-dependent CKD. Phase 3 studies of enarodustat are currently ongoing.
RCT Entities:
BACKGROUND:Enarodustat (JTZ-951) is an orally available hypoxia-inducible factor prolyl hydroxylase inhibitor that increases endogenous erythropoietin levels in the treatment of anemia associated with chronic kidney disease (CKD). OBJECTIVE: A phase 2b study of enarodustat to assess the hemoglobin (Hb) response, safety, and maintenance dosage was conducted in Japanese anemicpatients with hemodialysis-dependent CKD. METHODS: Subjects receiving a stable dose of an erythropoiesis-stimulating agent were randomized to receive once-daily enarodustat at a dose of 2, 4, or 6 mg or placebo in a double-blind manner for 6 weeks (Period 1) followed by 24-week open treatment with enarodustat, adjusted in the range of 2-8 mg to maintain Hb within a target range (10.0-12.0 g/dL; Period 2). RESULTS: Change in Hb from baseline increased with enarodustat dose in Period 1. In Period 2, the proportion of subjects who maintained their Hb level within the target range at the end of treatment was 65.1%. To maintain Hb levels within the target range over the course of Period 2, approximately 80% of subjects required 2 dose adjustments or fewer. Enarodustat decreased hepcidin and ferritin levels, increased total iron-binding capacity, and was generally well tolerated. CONCLUSIONS:Enarodustat corrected and maintained Hb levels in anemicpatients with hemodialysis-dependent CKD. Phase 3 studies of enarodustat are currently ongoing.
Authors: Deborah L Regidor; Joel D Kopple; Csaba P Kovesdy; Ryan D Kilpatrick; Charles J McAllister; Jason Aronovitz; Sander Greenland; Kamyar Kalantar-Zadeh Journal: J Am Soc Nephrol Date: 2006-04 Impact factor: 10.121
Authors: Peter A McCullough; Huiman X Barnhart; Jula K Inrig; Donal Reddan; Shelly Sapp; Uptal D Patel; Ajay K Singh; Lynda A Szczech; Robert M Califf Journal: Am J Nephrol Date: 2013-05-25 Impact factor: 3.754
Authors: Patrizia Natale; Suetonia C Palmer; Allison Jaure; Elisabeth M Hodson; Marinella Ruospo; Tess E Cooper; Deirdre Hahn; Valeria M Saglimbene; Jonathan C Craig; Giovanni Fm Strippoli Journal: Cochrane Database Syst Rev Date: 2022-08-25