PMID- 32719868
OWN - NLM
STAT- Publisher
LR  - 20240227
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Linking)
DP  - 2020 Jul 28
TI  - Vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, for 
      treatment of anemia of chronic kidney disease: two randomized Phase 2 trials in 
      Japanese patients.
LID - gfaa060 [pii]
LID - 10.1093/ndt/gfaa060 [doi]
AB  - BACKGROUND: Vadadustat is an investigational, oral hypoxia-inducible factor 
      prolyl hydroxylase inhibitor in development in Japan for the treatment of chronic 
      kidney disease (CKD)-induced anemia. METHODS: Two Phase 2, multicenter, 
      double-blind, placebo-controlled studies randomized Japanese patients with 
      nondialysis-dependent (NDD, n = 51) or dialysis-dependent (DD, n = 60) 
      CKD-induced anemia to once-daily vadadustat (150, 300 or 600 mg) or placebo. A 
      6-week, fixed-dose primary efficacy period was followed by a 10-week vadadustat 
      dose adjustment/maintenance period. The primary endpoint was the mean change in 
      hemoglobin (Hb) level from pretreatment to Week 6. RESULTS: Statistically 
      significant (P < 0.01) dose-dependent increases in mean Hb values were observed 
      at Week 6 in all vadadustat groups versus placebo [placebo and vadadustat 150, 
      300 and 600 mg: -0.47, 0.43, 1.13 and 1.62 (NDD-CKD) and -1.48, -0.28, 0.08 and 
      0.41 (DD-CKD), respectively]. By Week 16, 91% (NDD-CKD) and 71% (DD-CKD) of 
      vadadustat-treated participants achieved target Hb levels (10.0-12.0 g/dL) and 
      significant dose-dependent changes in iron utilization and mobilization 
      biomarkers were observed with vadadustat. During the primary efficacy period, the 
      incidence of treatment-emergent adverse events (AEs) with placebo and vadadustat 
      150, 300 and 600 mg was 36, 33, 58 and 54% (NDD-CKD) and 40, 53, 73 and 40% 
      (DD-CKD), respectively. The most common AEs during the primary efficacy period 
      were nausea and hypertension (NDD-CKD) and diarrhea, nasopharyngitis and shunt 
      stenosis (DD-CKD). Of 23 serious AEs in 18 patients, 1 was deemed related 
      (hepatic function abnormal); no deaths were reported. CONCLUSIONS: The efficacy 
      and safety results from these studies support the development of vadadustat for 
      the treatment of anemia in patients with CKD.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. 
      All rights reserved.
FAU - Nangaku, Masaomi
AU  - Nangaku M
AD  - Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
FAU - Farag, Youssef M K
AU  - Farag YMK
AD  - Clinical Development, Akebia Therapeutics Inc., Cambridge, MA, USA.
FAU - deGoma, Emil
AU  - deGoma E
AD  - Akebia Therapeutics Inc., Cambridge, MA, USA.
FAU - Luo, Wenli
AU  - Luo W
AD  - Biostatistics, Akebia Therapeutics Inc., Cambridge, MA, USA.
FAU - Vargo, Dennis
AU  - Vargo D
AD  - Clinical Development, Akebia Therapeutics Inc., Cambridge, MA, USA.
FAU - Khawaja, Zeeshan
AU  - Khawaja Z
AD  - Drug Safety and Pharmacovigilance, Akebia Therapeutics Inc., Cambridge, MA, USA.
LA  - eng
PT  - Journal Article
DEP - 20200728
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
SB  - IM
OTO - NOTNLM
OT  - anemia
OT  - chronic kidney disease
OT  - erythropoietin
OT  - hypoxia-inducible factor
OT  - prolyl-4-hydroxylase inhibitor
EDAT- 2020/07/29 06:00
MHDA- 2020/07/29 06:00
CRDT- 2020/07/29 06:00
PHST- 2019/09/25 00:00 [received]
PHST- 2020/07/29 06:00 [entrez]
PHST- 2020/07/29 06:00 [pubmed]
PHST- 2020/07/29 06:00 [medline]
AID - 5877009 [pii]
AID - 10.1093/ndt/gfaa060 [doi]
PST - aheadofprint
SO  - Nephrol Dial Transplant. 2020 Jul 28:gfaa060. doi: 10.1093/ndt/gfaa060.