This is a Phase 2, randomized, double-blind, placebo-controlled, dose-finding study to assess the efficacy, safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) of orally administered vadadustat in Japanese participants with anemia secondary to Dialysis-dependent Chronic Kidney Disease (DD-CKD).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
60
Daily oral dose
Daily oral dose
Unnamed facility
Aichi, Japan
Unnamed facility
Ehime, Japan
Unnamed facility
Fukui, Japan
Unnamed facility
Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period
The pre-treatment average value for Hb was defined as the average of 3 values obtained prior to treatment, i.e., the qualifying screening value and the Baseline value. Change from Pre-treatment was calculated as the Week 6 value minus the Pre-treatment value.
Time frame: Pre-treatment; Week 6
Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16
Time for this analysis was measured from Day 1 (Baseline) through the point in time during either the Primary Efficacy Period or the Dose Adjustment and Maintenance Period when a participant's Hb level achieved the target range of 10.0 to 12.0 g/dL.
Time frame: from Baseline up to Week 16
Mean Hb Levels at the End of the Primary Efficacy Period
Data are reported as mean of the actual Week 6 values.
Time frame: up to Week 6
Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period
Data are reported as mean of the actual Week 16 values.
Time frame: up to Week 16
Number of Participants Who Achieved the Target Hb Level of 10.0 to 12.0 g/dL at the End of the Dose Adjustment and Maintenance Period
Time frame: up to Week 16
Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period
A pre-treatment average value for Hb was defined as the average of 3 values obtained prior to dosing, i.e., the 2 qualifying screening values and the Baseline value. Change from Pre-treatment was calculated as the Week 16 value minus the Pre-treatment value.
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Hiroshima, Japan
Unnamed facility
Hokkaido, Japan
Unnamed facility
Hyōgo, Japan
Unnamed facility
Ibaraki, Japan
Unnamed facility
Kagoshima, Japan
Unnamed facility
Kochi, Japan
Unnamed facility
Miyagi, Japan
...and 8 more locations
Time frame: Pre-treatment; Week 16
Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 6
Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 16
Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 6
Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 16
Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 6
Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 16
Mean Change in Transferrin Saturation (TSAT) From Baseline to the End of the Primary Efficacy Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 6
Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 16
Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 6
Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 16
Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Primary Efficacy Period
Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.
Time frame: Baseline; Week 6
Number of Participants Who Required Rescue With RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period
Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study.
Time frame: Baseline; Week 16
Number of Participants Who Required Rescue With Erythropoiesis-Stimulating Agents (ESAs) From Baseline to the End of the Primary Efficacy Period
ESA rescue is defined as participants with ESA administration and 1) the participant experienced a clinically significant worsening of their anemia or symptoms of anemia, 2) the participant's Hb level is \<9.0 g/dL, and 3) reason for early study withdrawal of worsening of anemia requiring ESA rescue or blood transfusion. Participants who initiated rescue therapy (including ESAs) were required to stop study drug treatment and were discontinued from the study.
Time frame: Baseline; Week 6
Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period
ESA rescue is defined as participants with ESA administration and 1) the participant experienced a clinically significant worsening of their anemia or symptoms of anemia, 2) the participant's Hb level is \<9.0 g/dL, and 3) reason for early study withdrawal of worsening of anemia requiring ESA rescue or blood transfusion. Participants who initiated rescue therapy (including ESAs) were required to stop study drug treatment and were discontinued from the study.
Time frame: Baseline; Week 16
Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period
Increases in dose were not allowed during the 6-week Primary Efficacy Period.
Time frame: up to Week 16
Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4
Blood samples were collected for analysis.
Time frame: Week 4, pre-dose
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period
An adverse event (AE) was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. An AE included medical conditions, signs, and symptoms not previously observed in the participant that emerged during the protocol-specified AE reporting period, including signs or symptoms associated with pre-existing underlying conditions that were not present prior to the AE reporting period. An AE that met one or more of the following criteria or outcomes was classified as serious: death; life-threatening; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; was considered a medically important event not meeting the above criteria, but which could jeopardize a participant, or could require medical or surgical intervention to prevent one of the criteria listed in this definition.
Time frame: up to Week 6
Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period
An AE was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. An AE included medical conditions, signs, and symptoms not previously observed in the participant that emerged during the protocol-specified AE reporting period, including signs or symptoms associated with pre-existing underlying conditions that were not present prior to the AE reporting period. An AE that met one or more of the following criteria or outcomes was classified as serious: death; life-threatening; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; was considered a medically important event not meeting the above criteria, but which could jeopardize a participant, or could require medical or surgical intervention to prevent one of the criteria listed in this definition.
Time frame: up to Week 16