دورية أكاديمية
Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.
| العنوان: | Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study. |
|---|---|
| المؤلفون: | Provenzano R; St. John Hospital & Medical Center, Detroit, MI., Besarab A; FibroGen, Inc, San Francisco, CA., Wright S; US Renal Care, Pine Bluff, AR., Dua S; Valley Renal Medical Group, Northridge, CA., Zeig S; Pines Clinical Research, Pembroke Pines, FL., Nguyen P; US Renal Care, Ft Worth, TX., Poole L; FibroGen, Inc, San Francisco, CA., Saikali KG; FibroGen, Inc, San Francisco, CA., Saha G; FibroGen, Inc, San Francisco, CA., Hemmerich S; FibroGen, Inc, San Francisco, CA., Szczech L; FibroGen, Inc, San Francisco, CA., Yu KH; FibroGen, Inc, San Francisco, CA. Electronic address: pyu@fibrogen.com., Neff TB; FibroGen, Inc, San Francisco, CA. |
| المصدر: | American journal of kidney diseases : the official journal of the National Kidney Foundation [Am J Kidney Dis] 2016 Jun; Vol. 67 (6), pp. 912-24. Date of Electronic Publication: 2016 Feb 02. |
| نوع المنشور: | Clinical Trial, Phase II; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial |
| اللغة: | English |
| بيانات الدورية: | Publisher: W.B. Saunders Country of Publication: United States NLM ID: 8110075 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-6838 (Electronic) Linking ISSN: 02726386 NLM ISO Abbreviation: Am J Kidney Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Philadelphia Pa : W.B. Saunders Original Publication: New York, N.Y. : Grune & Stratton, c1981- |
| مواضيع طبية MeSH: | Renal Dialysis*, Anemia/*drug therapy , Epoetin Alfa/*therapeutic use , Glycine/*analogs & derivatives , Hematinics/*therapeutic use , Isoquinolines/*therapeutic use , Kidney Failure, Chronic/*complications , Kidney Failure, Chronic/*therapy, Adult ; Aged ; Aged, 80 and over ; Epoetin Alfa/administration & dosage ; Female ; Glycine/administration & dosage ; Glycine/therapeutic use ; Hematinics/administration & dosage ; Humans ; Isoquinolines/administration & dosage ; Male ; Middle Aged ; Time Factors ; Treatment Outcome ; Young Adult |
| مستخلص: | Background: Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. Study Design: Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. Setting & Participants: Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa. Intervention: Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. Outcomes: Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). Measurements: Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). Results: Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised. Limitations: Short treatment duration and small sample size. Conclusions: In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels. (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Hb correction; Hb maintenance; Hb response; Hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI); anemia; chronic kidney disease (CKD); dialysis; end-stage renal disease (ESRD); erythropoiesis; erythropoietin; hemoglobin (Hb); hepcidin; iron transport; randomized trial; roxadustat |
| المشرفين على المادة: | 0 (Hematinics) 0 (Isoquinolines) 64FS3BFH5W (Epoetin Alfa) TE7660XO1C (Glycine) X3O30D9YMX (roxadustat) |
| تواريخ الأحداث: | Date Created: 20160206 Date Completed: 20170531 Latest Revision: 20220331 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1053/j.ajkd.2015.12.020 |
| PMID: | 26846333 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1523-6838 |
|---|---|
| DOI: | 10.1053/j.ajkd.2015.12.020 |