Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents
| Autor: | Amit Sharma, Emil M. deGoma, Pablo E. Pergola, Geoffrey A. Block, Volker H. Haase, Glenn M. Chertow, Peter A. McCullough, Bradley J. Maroni, Zeeshan Khawaja |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Nausea Anemia medicine.medical_treatment hypoxia-inducible factor prolyl-4-hydroxylase inhibitor Glycine 030232 urology & nephrology 030204 cardiovascular system & hematology Gastroenterology Hemoglobins Young Adult 03 medical and health sciences 0302 clinical medicine Renal Dialysis Clinical Research Internal medicine vadadustat medicine Humans Erythropoiesis Renal Insufficiency Chronic Picolinic Acids Adverse effect Aged Transplantation hemodialysis business.industry Epoetin alfa Middle Aged Prognosis medicine.disease Nephrology Erythropoietin Hematinics Vomiting Female Hemodialysis ORIGINAL ARTICLES medicine.symptom business medicine.drug Kidney disease |
| Zdroj: | Nephrology Dialysis Transplantation |
| ISSN: | 1460-2385 0931-0509 |
| DOI: | 10.1093/ndt/gfy055 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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