PMID- 30852574
OWN - NLM
STAT- MEDLINE
DCOM- 20200527
LR  - 20200527
IS  - 1421-9670 (Electronic)
IS  - 0250-8095 (Print)
IS  - 0250-8095 (Linking)
VI  - 49
IP  - 4
DP  - 2019
TI  - Long-Term Efficacy and Safety of Molidustat for Anemia in Chronic Kidney Disease: 
      DIALOGUE Extension Studies.
PG  - 271-280
LID - 10.1159/000499111 [doi]
AB  - BACKGROUND: Molidustat, a novel hypoxia-inducible factor-prolyl hydroxylase 
      inhibitor, is being investigated for the treatment of anemia associated with 
      chronic kidney disease (CKD). The efficacy and safety of molidustat were recently 
      evaluated in three 16-week phase 2b studies. Here, we report the results of two 
      long-term extension studies of molidustat. METHODS: Both studies were 
      parallel-group, open-label, multicenter studies of </=36 months' duration, in 
      patients with anemia due to CKD, and included an erythropoiesis-stimulating agent 
      as active control. One study enrolled patients not receiving dialysis (n = 164), 
      and the other enrolled patients receiving hemodialysis (n = 88). The primary 
      efficacy variable for both studies was change in blood hemoglobin (Hb) level from 
      baseline to each post-baseline visit, and safety outcomes included adverse events 
      (AEs). RESULTS: In patients not on dialysis, the mean +/- SD Hb concentrations at 
      baseline were 11.28 +/- 0.55 g/dL for molidustat and 11.08 +/- 0.51 g/dL for 
      darbepoetin. The mean +/- SD blood Hb concentrations throughout the study (defined 
      as mean of each patient's overall study Hb levels) were 11.10 +/- 0.508 and 10.98 +/- 
      0.571 g/dL in patients treated with molidustat and darbepoetin, respectively. 
      Similar proportions of patients reported at least one AE in the molidustat 
      (85.6%) and darbepoetin (85.7%) groups. In patients on dialysis, mean +/- SD Hb 
      levels at baseline were 10.40 +/- 0.70 and 10.52 +/- 0.53 g/dL in the molidustat and 
      epoetin groups, respectively. The mean +/- SD blood Hb concentrations during the 
      study were 10.37 +/- 0.56 g/dL in the molidustat group and 10.52 +/- 0.47 g/dL in the 
      epoetin group. Proportions of patients who reported at least one AE were 91.2% in 
      the molidustat group and 93.3% in the epoetin group. CONCLUSIONS: Molidustat was 
      well tolerated for up to 36 months and appears to be an effective alternative to 
      darbepoetin and epoetin in the long-term management of anemia associated with 
      CKD.
CI  - (c) 2019 The Author(s) Published by S. Karger AG, Basel.
FAU - Akizawa, Tadao
AU  - Akizawa T
AD  - Division of Nephrology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan, akizawa@med.showa-u.ac.jp.
FAU - Macdougall, Iain C
AU  - Macdougall IC
AD  - Department of Renal Medicine, King's College Hospital, London, United Kingdom.
FAU - Berns, Jeffrey S
AU  - Berns JS
AD  - Perelman School of Medicine at the University of Pennsylvania, Hospital of the 
      University of Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Bernhardt, Thomas
AU  - Bernhardt T
AD  - Research & Development, Pharmaceuticals, Bayer AG, Berlin, Germany.
FAU - Staedtler, Gerald
AU  - Staedtler G
AD  - Research & Development, Pharmaceuticals, Bayer AG, Berlin, Germany.
FAU - Taguchi, Megumi
AU  - Taguchi M
AD  - Medical Affairs, Pulmonology & Cardiology, Bayer Yakuhin Ltd., Osaka, Japan.
FAU - Iekushi, Kazuma
AU  - Iekushi K
AD  - Medical Affairs, Pulmonology & Cardiology, Bayer Yakuhin Ltd., Osaka, Japan.
FAU - Krueger, Thilo
AU  - Krueger T
AD  - Research & Development, Pharmaceuticals, Bayer AG, Wuppertal, Germany.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20190308
PL  - Switzerland
TA  - Am J Nephrol
JT  - American journal of nephrology
JID - 8109361
RN  - 0 (Hematinics)
RN  - 0 (Hemoglobins)
RN  - 0 (Pyrazoles)
RN  - 0 (Triazoles)
RN  - 15UQ94PT4P (Darbepoetin alfa)
RN  - 64FS3BFH5W (Epoetin Alfa)
RN  - 9JH486CZ13 (molidustat)
SB  - IM
EIN - Am J Nephrol. 2019;50(2):160. PMID: 31295742
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anemia/blood/*drug therapy/etiology
MH  - Darbepoetin alfa/administration & dosage/adverse effects
MH  - Drug Administration Schedule
MH  - Epoetin Alfa/administration & dosage/adverse effects
MH  - Female
MH  - Hematinics/*administration & dosage/adverse effects
MH  - Hemoglobins/analysis
MH  - Humans
MH  - Long-Term Care/methods
MH  - Male
MH  - Middle Aged
MH  - Pyrazoles/*administration & dosage/adverse effects
MH  - Renal Dialysis
MH  - Renal Insufficiency, Chronic/blood/*complications/therapy
MH  - Time Factors
MH  - Treatment Outcome
MH  - Triazoles/*administration & dosage/adverse effects
PMC - PMC6518868
OTO - NOTNLM
OT  - Anemia
OT  - Chronic kidney disease
OT  - Efficacy
OT  - Molidustat
OT  - Safety
EDAT- 2019/03/11 06:00
MHDA- 2020/05/28 06:00
PMCR- 2019/03/08
CRDT- 2019/03/11 06:00
PHST- 2018/12/04 00:00 [received]
PHST- 2019/02/06 00:00 [accepted]
PHST- 2019/03/11 06:00 [pubmed]
PHST- 2020/05/28 06:00 [medline]
PHST- 2019/03/11 06:00 [entrez]
PHST- 2019/03/08 00:00 [pmc-release]
AID - 000499111 [pii]
AID - ajn-0049-0271 [pii]
AID - 10.1159/000499111 [doi]
PST - ppublish
SO  - Am J Nephrol. 2019;49(4):271-280. doi: 10.1159/000499111. Epub 2019 Mar 8.