Enarodustat, Conversion and Maintenance Therapy for Anemia in Hemodialysis Patients: A Randomized, Placebo-Controlled Phase 2b Trial Followed by Long-Term Trial
| Autor: | Takuhiro Yamaguchi, Ryosuke Koretomo, Hideki Hirakata, Yuya Miyazawa, Kazuo Maeda, Masaomi Nangaku, Tadao Akizawa, Masanobu Arai |
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| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Pyridines Anemia medicine.medical_treatment 030232 urology & nephrology 030204 cardiovascular system & hematology Placebo Gastroenterology Hypoxia-Inducible Factor-Proline Dioxygenases law.invention Hemoglobins 03 medical and health sciences 0302 clinical medicine Double-Blind Method Hepcidins Randomized controlled trial Maintenance therapy Renal Dialysis law Hepcidin Internal medicine Humans Medicine Enzyme Inhibitors Renal Insufficiency Chronic Aged Dose-Response Relationship Drug biology business.industry Middle Aged Triazoles Clinical Practice: Original Paper medicine.disease N-substituted Glycines Ferritins biology.protein Female Hemodialysis Hemoglobin business Kidney disease |
| Zdroj: | Nephron. 143:77-85 |
| ISSN: | 2235-3186 1660-8151 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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