Daprodustat for anemia: a 24-week, open-label, randomized controlled trial in participants with chronic kidney disease.

ABSTRACT: Background:This study assessed the short-term safety and efficacy of daprodustat (an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor) to achieve a target hemoglobin in patients with anemia of chronic kidney disease (CKD). Methods:Patients (n?=?252) with Stages 3-5 CKD not receiving dialysis were enrolled in this 24-week, multicenter trial [hemoglobin entry criteria: 8-10?g/dL (Cohort 1) or 8-11?g/dL (Cohort 2) for recombinant human erythropoietin (rhEPO)-naïve participants; 9-10.5?g/dL (Cohort 1) or 9-11.5?g/dL (Cohort 2) for rhEPO users]. rhEPO-naïve participants were randomized 3:1 to daprodustat (1, 2 or 4?mg) or control (rhEPO per standard of care). rhEPO users were randomized 1:1 to daprodustat 2?mg or control. Study medication was titrated to maintain hemoglobin 9-10.5?g/dL (Cohort 1) or 10-11.5?g/dL (Cohort 2). Hemoglobin, iron metabolism markers and safety parameters were measured every 4 weeks. Results:Mean hemoglobin levels at Week 24 were 10.2?g/dL (Cohort 1) and 10.9?g/dL (Cohort 2) in the daprodustat group and 10.7?g/dL (Cohort 1) and 11.0?g/dL (Cohort 2) in the control group. Participants had hemoglobin levels within the target range a median of 82% and 66% of the time between Weeks 12 and 24 in the daprodustat and control groups, respectively. The adverse event profile was consistent with clinical events in the CKD population. Conclusions:Daprodustat effectively maintained target hemoglobin over 24 weeks in CKD patients with anemia who were rhEPO naïve or had switched from existing rhEPO therapy.

SUBMITTER: Holdstock L 

PROVIDER: S-EPMC6366145 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature