دورية أكاديمية
Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD.
| العنوان: | Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD. |
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| المؤلفون: | Provenzano R; St. John Hospital and Medical Center, Detroit, Michigan., Besarab A; FibroGen, Inc., San Francisco, California., Sun CH; Apex Research of Riverside, Riverside, California., Diamond SA; San Antonio Kidney Disease Center, San Antonio, Texas., Durham JH; Palmetto Nephrology, Professional Association, Orangeburg, South Carolina., Cangiano JL; Nephrology Private Practice, San Juan, Puerto Rico., Aiello JR; Mountain Kidney and Hypertension Associates, Professional Association, Asheville, North Carolina; and., Novak JE; Division of Nephrology, Henry Ford Hospital, Detroit, Michigan., Lee T; FibroGen, Inc., San Francisco, California., Leong R; FibroGen, Inc., San Francisco, California., Roberts BK; FibroGen, Inc., San Francisco, California., Saikali KG; FibroGen, Inc., San Francisco, California., Hemmerich S; FibroGen, Inc., San Francisco, California., Szczech LA; FibroGen, Inc., San Francisco, California., Yu KP; FibroGen, Inc., San Francisco, California., Neff TB; FibroGen, Inc., San Francisco, California. |
| المصدر: | Clinical journal of the American Society of Nephrology : CJASN [Clin J Am Soc Nephrol] 2016 Jun 06; Vol. 11 (6), pp. 982-991. Date of Electronic Publication: 2016 Apr 19. |
| نوع المنشور: | Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wolters Kluwer Health Country of Publication: United States NLM ID: 101271570 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1555-905X (Electronic) Linking ISSN: 15559041 NLM ISO Abbreviation: Clin J Am Soc Nephrol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : Hagerstown, MD : Wolters Kluwer Health Original Publication: Washington, D.C. : American Society of Nephrology, c2005- |
| مواضيع طبية MeSH: | Anemia/*drug therapy , Enzyme Inhibitors/*therapeutic use , Glycine/*analogs & derivatives , Isoquinolines/*therapeutic use , Renal Insufficiency, Chronic/*complications, Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Anemia/blood ; Anemia/etiology ; C-Reactive Protein/metabolism ; Cholesterol/blood ; Enzyme Inhibitors/administration & dosage ; Enzyme Inhibitors/adverse effects ; Female ; Glycine/administration & dosage ; Glycine/adverse effects ; Glycine/therapeutic use ; Hemoglobins/metabolism ; Hepcidins/blood ; Humans ; Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors ; Isoquinolines/administration & dosage ; Isoquinolines/adverse effects ; Male ; Middle Aged |
| مستخلص: | Background and Objectives: Roxadustat (FG-4592), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, regulates iron metabolism, and reduces hepcidin, was evaluated in this phase 2b study for safety, efficacy, optimal dose, and dose frequency in patients with nondialysis CKD. Design, Setting, Participants, & Measurements: The 145 patients with nondialysis CKD and hemoglobin ≤10.5 g/dl were randomized into one of six cohorts of approximately 24 patients each with varying roxadustat starting doses (tiered weight and fixed amounts) and frequencies (two and three times weekly) followed by hemoglobin maintenance with roxadustat one to three times weekly. Treatment duration was 16 or 24 weeks. Intravenous iron was prohibited. The primary end point was the proportion of patients achieving hemoglobin increase of ≥1.0 g/dl from baseline and hemoglobin of ≥11.0 g/dl by week 17 (16 weeks of treatment). Secondary analyses included mean hemoglobin change from baseline, iron utilization, and serum lipids. Safety was evaluated by frequency/severity of adverse events. Results: Of the 145 patients enrolled, 143 were evaluable for efficacy. Overall, 92% of patients achieved hemoglobin response. Higher compared with lower starting doses led to earlier achievement of hemoglobin response. Roxadustat-induced hemoglobin increases were independent of baseline C-reactive protein levels and iron repletion status. Overall, over the first 16 treatment weeks, hepcidin levels decreased by 16.9% (P=0.004), reticulocyte hemoglobin content was maintained, and hemoglobin increased by a mean (±SD) of 1.83 (±0.09) g/dl (P<0.001). Overall mean total cholesterol level was reduced by a mean (±SD) of 26 (±30) mg/dl (P<0.001) after 8 weeks of therapy, independent of the use of statins or other lipid-lowering agents. No drug-related serious adverse events were reported. Conclusions: In patients with nondialysis CKD who were anemic, various starting dose regimens of roxadustat were well tolerated and achieved anemia correction with reduced serum hepcidin levels. After anemia correction, hemoglobin was maintained by roxadustat at various dose frequencies without intravenous iron supplementation. (Copyright © 2016 by the American Society of Nephrology.) |
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| فهرسة مساهمة: | Keywords: C-Reactive Protein; Erythropoiesis; Hemoglobins; Hepcidins; Humans; Iron; Renal Insufficiency, Chronic; anemia; chronic kidney disease; clinical trial |
| المشرفين على المادة: | 0 (Enzyme Inhibitors) 0 (Hemoglobins) 0 (Hepcidins) 0 (Isoquinolines) 9007-41-4 (C-Reactive Protein) 97C5T2UQ7J (Cholesterol) EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases) TE7660XO1C (Glycine) X3O30D9YMX (roxadustat) |
| تواريخ الأحداث: | Date Created: 20160421 Date Completed: 20171211 Latest Revision: 20230813 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC4891748 |
| DOI: | 10.2215/CJN.06890615 |
| PMID: | 27094610 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1555-905X |
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| DOI: | 10.2215/CJN.06890615 |