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Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents

BACKGROUND: Vadadustat, an inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain dioxygenases, is an oral investigational agent in development for the treatment of anemia secondary to chronic kidney disease. METHODS: In this open-label Phase 2 trial, vadadustat was evaluated in 94 subjec...

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Autores principales: Haase, Volker H, Chertow, Glenn M, Block, Geoffrey A, Pergola, Pablo E, deGoma, Emil M, Khawaja, Zeeshan, Sharma, Amit, Maroni, Bradley J, McCullough, Peter A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322440/
https://www.ncbi.nlm.nih.gov/pubmed/29672740
http://dx.doi.org/10.1093/ndt/gfy055
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author Haase, Volker H
Chertow, Glenn M
Block, Geoffrey A
Pergola, Pablo E
deGoma, Emil M
Khawaja, Zeeshan
Sharma, Amit
Maroni, Bradley J
McCullough, Peter A
author_facet Haase, Volker H
Chertow, Glenn M
Block, Geoffrey A
Pergola, Pablo E
deGoma, Emil M
Khawaja, Zeeshan
Sharma, Amit
Maroni, Bradley J
McCullough, Peter A
author_sort Haase, Volker H
collection PubMed
description BACKGROUND: Vadadustat, an inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain dioxygenases, is an oral investigational agent in development for the treatment of anemia secondary to chronic kidney disease. METHODS: In this open-label Phase 2 trial, vadadustat was evaluated in 94 subjects receiving hemodialysis, previously maintained on epoetin alfa. Subjects were sequentially assigned to one of three vadadustat dose cohorts by starting dose: 300 mg once daily (QD), 450 mg QD or 450 mg thrice weekly (TIW). The primary endpoint was mean hemoglobin (Hb) change from pre-baseline average to midtrial (Weeks 7–8) and end-of-trial (Weeks 15–16) and was analyzed using available data (no imputation). RESULTS: Overall, 80, 73 and 68% of subjects in the 300 mg QD, 450 mg QD, and 450 mg TIW dose cohorts respectively, completed the study. For all dose cohorts no statistically significant mean change in Hb from pre-baseline average was observed, and mean Hb concentrations—analyzed using available data—remained stable at mid- and end-of-trial. There was one subject with an Hb excursion >13 g/dL. Overall, 83% of subjects experienced an adverse event (AE); the proportion of subjects who experienced at least one AE was similar among the three dose cohorts. The most frequently reported AEs were nausea (11.7%), diarrhea (10.6%) and vomiting (9.6%). No deaths occurred during the study. No serious AEs were attributed to vadadustat. CONCLUSIONS: Vadadustat maintained mean Hb concentrations in subjects on hemodialysis previously receiving epoetin. These data support further investigation of vadadustat to assess its long-term safety and efficacy in subjects on hemodialysis.
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spelling pubmed-63224402019-01-10 Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents Haase, Volker H Chertow, Glenn M Block, Geoffrey A Pergola, Pablo E deGoma, Emil M Khawaja, Zeeshan Sharma, Amit Maroni, Bradley J McCullough, Peter A Nephrol Dial Transplant ORIGINAL ARTICLES BACKGROUND: Vadadustat, an inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain dioxygenases, is an oral investigational agent in development for the treatment of anemia secondary to chronic kidney disease. METHODS: In this open-label Phase 2 trial, vadadustat was evaluated in 94 subjects receiving hemodialysis, previously maintained on epoetin alfa. Subjects were sequentially assigned to one of three vadadustat dose cohorts by starting dose: 300 mg once daily (QD), 450 mg QD or 450 mg thrice weekly (TIW). The primary endpoint was mean hemoglobin (Hb) change from pre-baseline average to midtrial (Weeks 7–8) and end-of-trial (Weeks 15–16) and was analyzed using available data (no imputation). RESULTS: Overall, 80, 73 and 68% of subjects in the 300 mg QD, 450 mg QD, and 450 mg TIW dose cohorts respectively, completed the study. For all dose cohorts no statistically significant mean change in Hb from pre-baseline average was observed, and mean Hb concentrations—analyzed using available data—remained stable at mid- and end-of-trial. There was one subject with an Hb excursion >13 g/dL. Overall, 83% of subjects experienced an adverse event (AE); the proportion of subjects who experienced at least one AE was similar among the three dose cohorts. The most frequently reported AEs were nausea (11.7%), diarrhea (10.6%) and vomiting (9.6%). No deaths occurred during the study. No serious AEs were attributed to vadadustat. CONCLUSIONS: Vadadustat maintained mean Hb concentrations in subjects on hemodialysis previously receiving epoetin. These data support further investigation of vadadustat to assess its long-term safety and efficacy in subjects on hemodialysis. Oxford University Press 2019-01 2018-04-16 /pmc/articles/PMC6322440/ /pubmed/29672740 http://dx.doi.org/10.1093/ndt/gfy055 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle ORIGINAL ARTICLES
Haase, Volker H
Chertow, Glenn M
Block, Geoffrey A
Pergola, Pablo E
deGoma, Emil M
Khawaja, Zeeshan
Sharma, Amit
Maroni, Bradley J
McCullough, Peter A
Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents
title Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents
title_full Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents
title_fullStr Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents
title_full_unstemmed Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents
title_short Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents
title_sort effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents
topic ORIGINAL ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322440/
https://www.ncbi.nlm.nih.gov/pubmed/29672740
http://dx.doi.org/10.1093/ndt/gfy055
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