Abstract: SA-PO229
Randomized, Open-Label, Active-Controlled (Darbepoetin Alfa), Phase 3 Study of Vadadustat for Treating Anemia in Non-Dialysis-Dependent CKD Patients in Japan
Session Information
- Anemia and Iron Metabolism: Clinical
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 202 Anemia and Iron Metabolism: Clinical
Authors
- Nangaku, Masaomi, the University of Tokyo School of Medicine, Tokyo, Japan
- Kondo, Kazuoki, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
- Kokado, Yoshimasa, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
- Ueta, Kiichiro, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
- Kaneko, Genki, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
- Shiosaka, Masashi, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
- Kawaguchi, Yutaka, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan
- Komatsu, Yasuhiro, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan
Background
This open-label, active-controlled Phase 3 study (NCT03329196) evaluates the efficacy and safety of vadadustat (VDT), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, in 304 nondialysis dependent (NDD) chronic kidney disease (CKD) subjects with anemia in Japan for 52 weeks. Prespecified primary analysis results at 24 weeks are presented here.
Methods
NDD-CKD subjects with anemia receiving (conversion) or not receiving erythropoiesis stimulating agents (correction) were randomized to VDT (n=151) or darbepoetin alfa (DA) group (n=153). After initial VDT dose of 300 mg daily, doses were adjusted within 150–600 mg to achieve and maintain target hemoglobin (Hb) of 11–13 g/dL. Primary endpoint was average Hb at weeks 20 and 24. Noninferiority of VDT to DA was tested using mixed model for repeated measures. Iron parameters were measured. Safety was assessed up to 24 weeks.
Results
LSMean of the average Hb at weeks 20 and 24 was 11.66 (VDT: 95% CI, 11.49 to 11.84) and 11.93 (DA: 11.76 to 12.10) g/dL; 95% CI of both groups were within the target Hb of 11–13 g/dL. Difference in LSMean between the groups was −0.26 g/dL (−0.50 to −0.02); the 95% CI lower limit was above the predefined noninferiority margin of −0.75 g/dL, demonstrating the noninferiority of VDT to DA. VDT improved mean Hb from baseline of 10.68 to 11.27 g/dL at week 24 (conversion, n = 80) and 10.17 to 11.85 g/dL (correction, n = 71). VDT regimen was associated with significant increases in total iron-binding capacity and decreases in hepcidin from baseline to week 24, not found in the DA group. At least one adverse event (AE) was seen in 72.2% (VDT) and 73.2% (DA) subjects. The most common AEs in the VDT group were nasopharyngitis (VDT: 14.6%, DA: 12.4%), diarrhea (VDT: 10.6%, DA: 3.3%), and constipation (VDT: 5.3%, DA: 3.9%). The incidence rates of serious AEs were 13.9% (VDT) and 14.4% (DA). No serious AE was considered related to the study drug.
Conclusion
VDT was effective as DA in controlling Hb within the target range in both conversion and correction without new safety concerns, indicating the usefulness of VDT for treating anemia in Japanese NDD-CKD patients.
Funding
- Commercial Support – Mitsubishi Tanabe Pharma Corporation