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Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in Japanese Patients with
Masaomi Nangaku1, Kazuoki Kondo2, Yoshimasa Kokado2
1Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Insights
Vadadustat, an oral treatment for anemia in nondialysis-dependent chronic kidney disease (NDD-CKD), proved noninferior to darbepoetin alfa. This hypoxia-inducible factor prolyl hydroxylase inhibitor was well-tolerated in Japanese patients.
Area of Science:
- Nephrology
- Pharmacology
- Clinical Trials
Background:
- Anemia in chronic kidney disease (CKD) is often treated with erythropoiesis-stimulating agents, which carry risks of cardiovascular morbidity and mortality.
- Oral vadadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, showed promise in elevating hemoglobin levels in previous studies.
Purpose of the Study:
- To evaluate the noninferiority of oral vadadustat compared to subcutaneous darbepoetin alfa in Japanese adults with anemia and nondialysis-dependent CKD (NDD-CKD).
- To assess the efficacy and safety of vadadustat over 52 weeks.
Main Methods:
- A phase 3, open-label, active-controlled noninferiority trial randomized 304 Japanese adults with anemia in NDD-CKD.
- Participants received either oral vadadustat or subcutaneous darbepoetin alfa for 52 weeks.
- Primary efficacy endpoint was average hemoglobin at weeks 20 and 24; safety data included adverse events.
Main Results:
- Vadadustat demonstrated noninferiority to darbepoetin alfa, with average hemoglobin levels within the target range (11.0-13.0 g/dl) for both groups.
- The lower 95% confidence limit for the difference between groups was above the predefined noninferiority margin, confirming noninferiority.
- Similar proportions of patients experienced adverse events (AEs) and serious AEs; common AEs with vadadustat included nasopharyngitis, diarrhea, and constipation.
Conclusions:
- Vadadustat is noninferior to darbepoetin alfa for treating anemia in Japanese patients with NDD-CKD.
- Vadadustat demonstrated sustained efficacy in maintaining hemoglobin levels up to 52 weeks.
- Vadadustat was generally well tolerated, suggesting its potential as an alternative treatment option.
Background:
Standard care for treating anemia in patients with CKD includes use of erythropoiesis-stimulating agents, which sometimes involves increased risks of cardiovascular morbidity and mortality. Previous studies in patients with anemia and nondialysis-dependent CKD (NDD-CKD) found significantly elevated hemoglobin levels with use of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, compared with placebo.
Methods:
In this phase 3, open-label, active-controlled noninferiority trial, we randomized 304 Japanese adults with anemia in NDD-CKD (including erythropoiesis-stimulating agent users and nonusers) to oral vadadustat or subcutaneous darbepoetin alfa for 52 weeks. The primary efficacy end point was average hemoglobin at weeks 20 and 24. Safety data included adverse events (AEs) and serious AEs.
Results:
A total of 151 participants received vadadustat and 153 received darbepoetin alfa. Least squares mean of the average hemoglobin at weeks 20 and 24 was 11.66 (95% confidence interval [95% CI], 11.49 to 11.84) g/dl for vadadustat and 11.93 (95% CI, 11.76 to 12.10) g/dl for darbepoetin alfa. The 95% CIs for both treatments were within the target hemoglobin range (11.0-13.0 g/dl), and the lower 95% confidence limit for the difference between groups (-0.50 g/dl) was above the predefined noninferiority margin (-0.75 g/dl), demonstrating noninferiority of vadadustat to darbepoetin alfa. Similar proportions of patients in each group reported AEs and serious AEs. The most frequent AEs with vadadustat were nasopharyngitis, diarrhea, and constipation.
Conclusions:
In Japanese patients with NDD-CKD, vadadustat was noninferior to darbepoetin alfa, was effective up to week 52 in terms of average hemoglobin, and was generally well tolerated. These results suggest that vadadustat may be a potential treatment for anemia in this patient population.
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