Anemia, Non-dialysis Dependent Chronic Kidney Disease
Conditions
Keywords
Anemia, kidney, non-dialysis dependent chronic kidney disease, CKD, NDD-CKD, renal, vadadustat, AKB-6548, hypoxia-inducible factor, hypoxia-inducible factor (HIF), HIF, prolyl-hydroxylase inhibitor (PHI), PHI, Japan, Japanese, Akebia (AKB)
Brief summary
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 Non-dialysis Dependent Chronic Kidney Disease (NDD-CKD).
Interventions
DRUGVadadustat
DRUGPlacebo
Sponsors
Akebia Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female Japanese participants ≥20 years of age * Diagnosis of chronic kidney disease (CKD) based on an estimated glomerular filtration rate ≤60 milliliters per minute per 1.73 meters squared (mL/min/1.73 m\^2) * Hemoglobin (Hb) ≤10.5 grams per deciliter (g/dL) * Not currently being treated with dialysis and not expected to start dialysis within 3 months of screening
Exclusion criteria
* Anemia due to a cause other than CKD or presence of active bleeding or recent blood loss * Sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia * Red blood cell transfusion within 4 weeks prior to or during screening * Intravenous iron within 4 weeks prior to or during screening * Any use of erythropoiesis-stimulating agents within 6 weeks prior to or during screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period | Pre-treatment; Week 6 | The pre-treatment value for Hb was defined as the average of 2 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Hb Levels at the End of the Primary Efficacy Period | up to Week 6 | Data are reported as mean of the actual Week 6 values. |
| Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period | up to Week 16 | Data are reported as mean of the actual Week 16 values. |
| 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 | up to Week 16 | — |
| Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period | Pre-treatment; Week 16 | The pre-treatment value for Hb was defined as the average of 2 values obtained prior to treatment, i.e., the qualifying screening value and the Baseline value. Change from Pre-treatment was calculated as the Week 16 value minus the Pre-treatment value. |
| Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period | Baseline; Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | Baseline; Week 16 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period | Baseline; Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Baseline; Week 16 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period | Baseline; Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | Baseline; Week 16 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Mean Change in Transferrin Saturation (TSAT) From Baseline to the End of the Primary Efficacy Period | Baseline; Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period | Baseline; Week 16 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16 | 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. |
| Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Baseline; Week 16 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Number of Participants Who Required Rescue With Erythropoiesis-stimulating Agents (ESAs) From Baseline to the End of the Primary Efficacy Period | Baseline; Week 6 | 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. |
| Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period | Baseline; Week 16 | 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. |
| Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Primary Efficacy Period | Baseline; Week 6 | Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study. |
| Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period | Baseline; Week 16 | Participants who initiated rescue therapy (including RBC transfusion) were required to stop study drug treatment and were discontinued from the study. |
| Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | Baseline to Week 16 | Increases in dose were not allowed during the 6-week Primary Efficacy Period. |
| Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6 | Baseline to Week 6 | Iron sufficiency was defined as ferritin ≥50 ng/mL and TSAT ≥20%. |
| Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Baseline to Week 16 | Iron sufficiency was defined as ferritin ≥50 ng/mL and TSAT ≥20%. |
| Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4 | Week 4, pre-dose | Blood samples were collected for analysis. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period | up to Week 6 | 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. |
| Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | up to Week 16 | 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. |
| Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period | Baseline; Week 6 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vadadustat 150 mg Participants were randomized to receive vadadustat 150 milligrams (mg), administered as 1 tablet once daily (QD), for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target hemoglobin (Hb) of 10.0 to 12.0 grams/deciliter (g/dL) based on dose adjustment guidelines. | 12 |
| Vadadustat 300 mg Participants were randomized to receive vadadustat 300 mg, administered as 2 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines. | 12 |
| Vadadustat 600 mg Participants were randomized to receive vadadustat 600 mg, administered as 4 tablets QD, for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines. | 13 |
| Placebo to Vadadustat 150 mg Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 150 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines. | 5 |
| Placebo to Vadadustat 300 mg Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 300 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines. | 4 |
| Placebo to Vadadustat 600 mg Participants were randomized to receive matching placebo for 6 weeks during the Primary Efficacy Period. During the 10-week Dose Adjustment and Maintenance Period, participants randomized to receive placebo in the 6-week Efficacy Period were switched to vadadustat 600 mg, and the dose was adjusted to achieve a target Hb of 10.0 to 12.0 g/dL based on dose adjustment guidelines. | 5 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Dose Adjustment and Maintenance Period | Investigator discretion | 1 | 2 | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Vadadustat 150 mg | Vadadustat 300 mg | Vadadustat 600 mg | Placebo to Vadadustat 150 mg | Placebo to Vadadustat 300 mg | Placebo to Vadadustat 600 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 71.9 years STANDARD_DEVIATION 10.33 | 65.8 years STANDARD_DEVIATION 11.53 | 71.5 years STANDARD_DEVIATION 12.84 | 73.4 years STANDARD_DEVIATION 3.05 | 68.0 years STANDARD_DEVIATION 21.21 | 72.2 years STANDARD_DEVIATION 8.64 | 70.2 years STANDARD_DEVIATION 11.55 |
| Hemoglobin Levels | 9.958 grams per deciliter (g/dL) STANDARD_DEVIATION 0.8051 | 9.492 grams per deciliter (g/dL) STANDARD_DEVIATION 0.8867 | 9.500 grams per deciliter (g/dL) STANDARD_DEVIATION 0.8446 | 10.280 grams per deciliter (g/dL) STANDARD_DEVIATION 0.9365 | 9.625 grams per deciliter (g/dL) STANDARD_DEVIATION 0.6551 | 9.680 grams per deciliter (g/dL) STANDARD_DEVIATION 0.8198 | 9.710 grams per deciliter (g/dL) STANDARD_DEVIATION 0.841 |
| Race and Ethnicity Not Collected | — | — | — | — | — | — | 0 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 8 Participants | 1 Participants | 1 Participants | 2 Participants | 22 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 5 Participants | 4 Participants | 3 Participants | 3 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 5 | 0 / 4 | 0 / 5 |
| other Total, other adverse events | 4 / 12 | 7 / 12 | 7 / 13 | 0 / 5 | 2 / 4 | 3 / 5 | 9 / 12 | 10 / 12 | 6 / 13 | 2 / 5 | 2 / 4 | 2 / 5 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 12 | 5 / 12 | 2 / 13 | 1 / 5 | 1 / 4 | 2 / 5 |
Outcome results
Primary
Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period
The pre-treatment value for Hb was defined as the average of 2 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
Population: Modified Intent-to-Treat Population (mITT): all randomized participants who received at least 1 dose of study medication, had a pre-treatment Hb average, and at least one post-Baseline Hb measurement. The mITT Population was based on the treatment to which participants were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vadadustat 150 | Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period | 0.43 grams per deciliter (g/dL) | Standard Error 0.224 |
| Vadadustat 300 mg | Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period | 1.13 grams per deciliter (g/dL) | Standard Error 0.223 |
| Vadadustat 600 mg | Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period | 1.62 grams per deciliter (g/dL) | Standard Error 0.215 |
| Placebo | Mean Change in Hemoglobin (Hb) Levels From Pre-treatment to the End of the Primary Efficacy Period | -0.47 grams per deciliter (g/dL) | Standard Error 0.206 |
p-value: 0.004595% CI: [0.29, 1.51]ANCOVA
p-value: <0.000195% CI: [0.98, 2.21]ANCOVA
p-value: <0.000195% CI: [1.49, 2.7]ANCOVA
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 150 | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Ferritin | -79.45 ng/mL | Standard Deviation 39.655 |
| Vadadustat 150 | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Hepcidin | -29.522 ng/mL | Standard Deviation 22.7101 |
| Vadadustat 300 mg | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Ferritin | -62.35 ng/mL | Standard Deviation 36.808 |
| Vadadustat 300 mg | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Hepcidin | -23.061 ng/mL | Standard Deviation 53.0161 |
| Vadadustat 600 mg | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Ferritin | -59.68 ng/mL | Standard Deviation 59.843 |
| Vadadustat 600 mg | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Hepcidin | -2.502 ng/mL | Standard Deviation 21.266 |
| Placebo | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Hepcidin | -9.464 ng/mL | Standard Deviation 19.1361 |
| Placebo | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Ferritin | -69.26 ng/mL | Standard Deviation 46.519 |
| Placebo to Vadadustat 300 mg | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Ferritin | -146.63 ng/mL | Standard Deviation 34.261 |
| Placebo to Vadadustat 300 mg | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Hepcidin | -38.920 ng/mL | Standard Deviation 23.4788 |
| Placebo to Vadadustat 600 mg | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Hepcidin | -9.745 ng/mL | Standard Deviation 9.21 |
| Placebo to Vadadustat 600 mg | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Dose Adjustment and Maintenance Period | Ferritin | -59.43 ng/mL | Standard Deviation 13.618 |
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 150 | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period | Ferritin | -38.48 nanograms per milliliter (ng/mL) | Standard Deviation 34.227 |
| Vadadustat 150 | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period | Hepcidin | -24.622 nanograms per milliliter (ng/mL) | Standard Deviation 20.0165 |
| Vadadustat 300 mg | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period | Hepcidin | -40.819 nanograms per milliliter (ng/mL) | Standard Deviation 27.2486 |
| Vadadustat 300 mg | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period | Ferritin | -69.36 nanograms per milliliter (ng/mL) | Standard Deviation 49.965 |
| Vadadustat 600 mg | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period | Ferritin | -101.54 nanograms per milliliter (ng/mL) | Standard Deviation 57.697 |
| Vadadustat 600 mg | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period | Hepcidin | -37.964 nanograms per milliliter (ng/mL) | Standard Deviation 21.0819 |
| Placebo | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period | Ferritin | -11.44 nanograms per milliliter (ng/mL) | Standard Deviation 31.408 |
| Placebo | Mean Change in Ferritin and Hepcidin From Baseline to the End of the Primary Efficacy Period | Hepcidin | -3.824 nanograms per milliliter (ng/mL) | Standard Deviation 18.4986 |
Comparison: Ferritinp-value: 0.108ANCOVA
Comparison: Ferritinp-value: 0.0002ANCOVA
Comparison: Ferritinp-value: <0.0001ANCOVA
Comparison: Hepcidinp-value: 0.0672ANCOVA
Comparison: Hepcidinp-value: 0.0004ANCOVA
Comparison: Hepcidinp-value: <0.0001ANCOVA
Secondary
Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period
The pre-treatment value for Hb was defined as the average of 2 values obtained prior to treatment, i.e., the qualifying screening value and the Baseline value. Change from Pre-treatment was calculated as the Week 16 value minus the Pre-treatment value.
Time frame: Pre-treatment; Week 16
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vadadustat 150 | Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period | 0.982 g/dL | Standard Deviation 0.3676 |
| Vadadustat 300 mg | Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period | 1.610 g/dL | Standard Deviation 1.1692 |
| Vadadustat 600 mg | Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period | 1.779 g/dL | Standard Deviation 0.8117 |
| Placebo | Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period | 0.790 g/dL | Standard Deviation 0.307 |
| Placebo to Vadadustat 300 mg | Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period | 1.538 g/dL | Standard Deviation 0.525 |
| Placebo to Vadadustat 600 mg | Mean Change in Hb Between Pre-treatment and the End of the Dose Adjustment and Maintenance Period | 2.075 g/dL | Standard Deviation 0.2784 |
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 150 | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Hematocrit | 3.28 percentage | Standard Deviation 1.947 |
| Vadadustat 150 | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Reticulocytes | -0.02 percentage | Standard Deviation 0.232 |
| Vadadustat 300 mg | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Hematocrit | 5.17 percentage | Standard Deviation 4.991 |
| Vadadustat 300 mg | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Reticulocytes | 0.07 percentage | Standard Deviation 0.442 |
| Vadadustat 600 mg | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Hematocrit | 5.39 percentage | Standard Deviation 2.844 |
| Vadadustat 600 mg | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Reticulocytes | -0.18 percentage | Standard Deviation 0.279 |
| Placebo | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Hematocrit | 2.32 percentage | Standard Deviation 1.827 |
| Placebo | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Reticulocytes | 0.28 percentage | Standard Deviation 0.893 |
| Placebo to Vadadustat 300 mg | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Hematocrit | 5.80 percentage | Standard Deviation 1.566 |
| Placebo to Vadadustat 300 mg | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Reticulocytes | 0.15 percentage | Standard Deviation 0.238 |
| Placebo to Vadadustat 600 mg | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Hematocrit | 6.05 percentage | Standard Deviation 1.997 |
| Placebo to Vadadustat 600 mg | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Dose Adjustment and Maintenance Period | Reticulocytes | -0.18 percentage | Standard Deviation 0.377 |
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 150 | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period | Hematocrit | 2.13 percentage | Standard Error 0.696 |
| Vadadustat 150 | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period | Reticulocytes | 0.16 percentage | Standard Error 0.111 |
| Vadadustat 300 mg | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period | Reticulocytes | 0.28 percentage | Standard Error 0.111 |
| Vadadustat 300 mg | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period | Hematocrit | 4.13 percentage | Standard Error 0.696 |
| Vadadustat 600 mg | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period | Hematocrit | 6.07 percentage | Standard Error 0.667 |
| Vadadustat 600 mg | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period | Reticulocytes | 0.19 percentage | Standard Error 0.107 |
| Placebo | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period | Hematocrit | -1.17 percentage | Standard Error 0.643 |
| Placebo | Mean Change in Hematocrit and Reticulocytes From Baseline to the End of the Primary Efficacy Period | Reticulocytes | 0.25 percentage | Standard Error 0.103 |
Comparison: Hematocritp-value: 0.00195% CI: [1.4, 5.2]ANCOVA
Comparison: Hematocritp-value: <0.000195% CI: [3.38, 7.22]ANCOVA
Comparison: Hematocritp-value: <0.000195% CI: [5.37, 9.11]ANCOVA
Comparison: Reticulocytesp-value: 0.588995% CI: [-0.39, 0.22]ANCOVA
Comparison: Reticulocytesp-value: 0.807495% CI: [-0.27, 0.34]ANCOVA
Comparison: Reticulocytesp-value: 0.695295% CI: [-0.36, 0.24]ANCOVA
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 150 | Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | Iron | 11.7 μg/dL | Standard Deviation 38.25 |
| Vadadustat 150 | Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | TIBC | 51.8 μg/dL | Standard Deviation 48.41 |
| Vadadustat 300 mg | Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | Iron | 3.5 μg/dL | Standard Deviation 31.17 |
| Vadadustat 300 mg | Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | TIBC | 43.4 μg/dL | Standard Deviation 42.77 |
| Vadadustat 600 mg | Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | Iron | 11.5 μg/dL | Standard Deviation 28.56 |
| Vadadustat 600 mg | Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | TIBC | 42.8 μg/dL | Standard Deviation 28.28 |
| Placebo | Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | Iron | -1.4 μg/dL | Standard Deviation 21.82 |
| Placebo | Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | TIBC | 47.6 μg/dL | Standard Deviation 21.71 |
| Placebo to Vadadustat 300 mg | Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | Iron | 5.5 μg/dL | Standard Deviation 24.66 |
| Placebo to Vadadustat 300 mg | Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | TIBC | 73.5 μg/dL | Standard Deviation 39.95 |
| Placebo to Vadadustat 600 mg | Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | Iron | 5.8 μg/dL | Standard Deviation 25.59 |
| Placebo to Vadadustat 600 mg | Mean Change in Iron and TIBC From Baseline to the End of the Dose Adjustment and Maintenance Period | TIBC | 44.5 μg/dL | Standard Deviation 43.19 |
Secondary
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
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 150 | Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period | Iron | -1.8 micrograms per deciliter (μg/dL) | Standard Deviation 19.58 |
| Vadadustat 150 | Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period | TIBC | 44.9 micrograms per deciliter (μg/dL) | Standard Deviation 32.9 |
| Vadadustat 300 mg | Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period | TIBC | 75.2 micrograms per deciliter (μg/dL) | Standard Deviation 35.6 |
| Vadadustat 300 mg | Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period | Iron | -2.4 micrograms per deciliter (μg/dL) | Standard Deviation 20.75 |
| Vadadustat 600 mg | Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period | Iron | 4.4 micrograms per deciliter (μg/dL) | Standard Deviation 30.82 |
| Vadadustat 600 mg | Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period | TIBC | 93.8 micrograms per deciliter (μg/dL) | Standard Deviation 44.74 |
| Placebo | Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period | Iron | -7.4 micrograms per deciliter (μg/dL) | Standard Deviation 19.92 |
| Placebo | Mean Change in Iron and Total Iron Binding Capacity (TIBC) From Baseline to the End of the Primary Efficacy Period | TIBC | 7.6 micrograms per deciliter (μg/dL) | Standard Deviation 23.55 |
Comparison: Ironp-value: 0.3702ANCOVA
Comparison: Ironp-value: 0.5524ANCOVA
Comparison: Ironp-value: 0.1589ANCOVA
Comparison: TIBCp-value: 0.0092ANCOVA
Comparison: TIBCp-value: <0.0001ANCOVA
Comparison: TIBCp-value: <0.0001ANCOVA
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 150 | Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | RBC Count | 0.305 10^6 cells/μL | Standard Deviation 0.187 |
| Vadadustat 150 | Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | Absolute Reticulocyte Count | 0.003078 10^6 cells/μL | Standard Deviation 0.0094008 |
| Vadadustat 300 mg | Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | RBC Count | 0.476 10^6 cells/μL | Standard Deviation 0.4406 |
| Vadadustat 300 mg | Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | Absolute Reticulocyte Count | 0.008001 10^6 cells/μL | Standard Deviation 0.0156884 |
| Vadadustat 600 mg | Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | RBC Count | 0.593 10^6 cells/μL | Standard Deviation 0.3186 |
| Vadadustat 600 mg | Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | Absolute Reticulocyte Count | 0.000196 10^6 cells/μL | Standard Deviation 0.0085029 |
| Placebo | Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | RBC Count | 0.186 10^6 cells/μL | Standard Deviation 0.2165 |
| Placebo | Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | Absolute Reticulocyte Count | 0.010716 10^6 cells/μL | Standard Deviation 0.0279909 |
| Placebo to Vadadustat 300 mg | Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | RBC Count | 0.438 10^6 cells/μL | Standard Deviation 0.2175 |
| Placebo to Vadadustat 300 mg | Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | Absolute Reticulocyte Count | 0.009703 10^6 cells/μL | Standard Deviation 0.0103348 |
| Placebo to Vadadustat 600 mg | Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | RBC Count | 0.608 10^6 cells/μL | Standard Deviation 0.1771 |
| Placebo to Vadadustat 600 mg | Mean Change in RBC Count and Absolute Reticulocyte Count From Baseline to the End of the Dose Adjustment and Maintenance Period | Absolute Reticulocyte Count | 0.000595 10^6 cells/μL | Standard Deviation 0.0171563 |
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 150 | Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period | RBC Count | 0.17 10^6 cells/microliter (μL) | Standard Error 0.075 |
| Vadadustat 150 | Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period | Absolute Reticulocyte Count | 0.01 10^6 cells/microliter (μL) | Standard Error 0.004 |
| Vadadustat 300 mg | Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period | Absolute Reticulocyte Count | 0.01 10^6 cells/microliter (μL) | Standard Error 0.003 |
| Vadadustat 300 mg | Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period | RBC Count | 0.34 10^6 cells/microliter (μL) | Standard Error 0.075 |
| Vadadustat 600 mg | Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period | RBC Count | 0.48 10^6 cells/microliter (μL) | Standard Error 0.073 |
| Vadadustat 600 mg | Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period | Absolute Reticulocyte Count | 0.01 10^6 cells/microliter (μL) | Standard Error 0.003 |
| Placebo | Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period | RBC Count | -0.17 10^6 cells/microliter (μL) | Standard Error 0.07 |
| Placebo | Mean Change in Red Blood Cell (RBC) Count and Absolute Reticulocyte Count From Baseline to the End of the Primary Efficacy Period | Absolute Reticulocyte Count | 0.01 10^6 cells/microliter (μL) | Standard Error 0.003 |
Comparison: RBC Countp-value: 0.001895% CI: [0.13, 0.55]ANCOVA
Comparison: RBC Countp-value: <0.000195% CI: [0.3, 0.72]ANCOVA
Comparison: RBC Countp-value: <0.000195% CI: [0.45, 0.86]ANCOVA
Comparison: Absolute Reticulocyte Countp-value: 0.780495% CI: [-0.01, 0.01]ANCOVA
Comparison: Absolute Reticulocyte Countp-value: 0.098695% CI: [0, 0.02]ANCOVA
Comparison: Absolute Reticulocyte Countp-value: 0.166195% CI: [0, 0.02]ANCOVA
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vadadustat 150 | Mean Change in Transferrin Saturation (TSAT) From Baseline to the End of the Primary Efficacy Period | -4.96 percentage | Standard Deviation 7.343 |
| Vadadustat 300 mg | Mean Change in Transferrin Saturation (TSAT) From Baseline to the End of the Primary Efficacy Period | -7.31 percentage | Standard Deviation 8.38 |
| Vadadustat 600 mg | Mean Change in Transferrin Saturation (TSAT) From Baseline to the End of the Primary Efficacy Period | -6.78 percentage | Standard Deviation 10.609 |
| Placebo | Mean Change in Transferrin Saturation (TSAT) From Baseline to the End of the Primary Efficacy Period | -4.72 percentage | Standard Deviation 8.931 |
p-value: 0.9092ANCOVA
p-value: 0.1484ANCOVA
p-value: 0.1313ANCOVA
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vadadustat 150 | Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period | -1.47 percentage | Standard Deviation 10.365 |
| Vadadustat 300 mg | Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period | -2.68 percentage | Standard Deviation 13.201 |
| Vadadustat 600 mg | Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period | -0.19 percentage | Standard Deviation 9.857 |
| Placebo | Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period | -7.00 percentage | Standard Deviation 12.247 |
| Placebo to Vadadustat 300 mg | Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period | -5.03 percentage | Standard Deviation 11.342 |
| Placebo to Vadadustat 600 mg | Mean Change in TSAT From Baseline to the End of the Dose Adjustment and Maintenance Period | -2.68 percentage | Standard Deviation 10.608 |
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vadadustat 150 | Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period | 10.973 g/dL | Standard Deviation 0.5711 |
| Vadadustat 300 mg | Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period | 11.230 g/dL | Standard Deviation 0.7514 |
| Vadadustat 600 mg | Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period | 11.342 g/dL | Standard Deviation 0.6473 |
| Placebo | Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period | 10.860 g/dL | Standard Deviation 0.5857 |
| Placebo to Vadadustat 300 mg | Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period | 11.425 g/dL | Standard Deviation 0.9179 |
| Placebo to Vadadustat 600 mg | Mean Hb Levels at the End of the Dose Adjustment and Maintenance Period | 11.950 g/dL | Standard Deviation 0.6608 |
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vadadustat 150 | Mean Hb Levels at the End of the Primary Efficacy Period | 10.392 g/dL | Standard Deviation 0.728 |
| Vadadustat 300 mg | Mean Hb Levels at the End of the Primary Efficacy Period | 10.675 g/dL | Standard Deviation 1.2693 |
| Vadadustat 600 mg | Mean Hb Levels at the End of the Primary Efficacy Period | 11.162 g/dL | Standard Deviation 1.1169 |
| Placebo | Mean Hb Levels at the End of the Primary Efficacy Period | 9.421 g/dL | Standard Deviation 0.9242 |
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat 150 | 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 | 11 Participants |
| Vadadustat 300 mg | 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 | 8 Participants |
| Vadadustat 600 mg | 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 | 11 Participants |
| Placebo | 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 | 5 Participants |
| Placebo to Vadadustat 300 mg | 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 | 3 Participants |
| Placebo to Vadadustat 600 mg | 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 | 2 Participants |
Secondary
Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16
Iron sufficiency was defined as ferritin ≥50 ng/mL and TSAT ≥20%.
Time frame: Baseline to Week 16
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat 150 | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Iron sufficiency maintained | 6 Participants |
| Vadadustat 150 | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Iron sufficiency not maintained | 6 Participants |
| Vadadustat 300 mg | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Iron sufficiency maintained | 2 Participants |
| Vadadustat 300 mg | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Iron sufficiency not maintained | 10 Participants |
| Vadadustat 600 mg | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Iron sufficiency maintained | 4 Participants |
| Vadadustat 600 mg | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Iron sufficiency not maintained | 9 Participants |
| Placebo | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Iron sufficiency maintained | 1 Participants |
| Placebo | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Iron sufficiency not maintained | 4 Participants |
| Placebo to Vadadustat 300 mg | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Iron sufficiency maintained | 1 Participants |
| Placebo to Vadadustat 300 mg | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Iron sufficiency not maintained | 3 Participants |
| Placebo to Vadadustat 600 mg | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Iron sufficiency maintained | 0 Participants |
| Placebo to Vadadustat 600 mg | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 16 | Iron sufficiency not maintained | 5 Participants |
Secondary
Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6
Iron sufficiency was defined as ferritin ≥50 ng/mL and TSAT ≥20%.
Time frame: Baseline to Week 6
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat 150 | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6 | Iron sufficiency maintained | 7 Participants |
| Vadadustat 150 | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6 | Iron sufficiency not maintained | 5 Participants |
| Vadadustat 300 mg | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6 | Iron sufficiency not maintained | 8 Participants |
| Vadadustat 300 mg | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6 | Iron sufficiency maintained | 4 Participants |
| Vadadustat 600 mg | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6 | Iron sufficiency not maintained | 9 Participants |
| Vadadustat 600 mg | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6 | Iron sufficiency maintained | 4 Participants |
| Placebo | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6 | Iron sufficiency maintained | 9 Participants |
| Placebo | Number of Participants Who Maintained Iron Sufficiency From Baseline to Week 6 | Iron sufficiency not maintained | 5 Participants |
p-value: 0.0895Fisher Exact
p-value: 1Fisher Exact
p-value: 0.3845Fisher Exact
Secondary
Number of Participants Who Required Rescue With a 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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat 150 | Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 Participants |
| Vadadustat 300 mg | Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period | 1 Participants |
| Vadadustat 600 mg | Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period | 1 Participants |
| Placebo | Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 Participants |
| Placebo to Vadadustat 300 mg | Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 Participants |
| Placebo to Vadadustat 600 mg | Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Dose Adjustment and Maintenance Period | 1 Participants |
Secondary
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
Population: mITT Population. Only participant with available data were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat 150 | Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Primary Efficacy Period | 0 Participants |
| Vadadustat 300 mg | Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Primary Efficacy Period | 0 Participants |
| Vadadustat 600 mg | Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Primary Efficacy Period | 0 Participants |
| Placebo | Number of Participants Who Required Rescue With a RBC Transfusion From Baseline to the End of the Primary Efficacy Period | 0 Participants |
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat 150 | Number of Participants Who Required Rescue With Erythropoiesis-stimulating Agents (ESAs) From Baseline to the End of the Primary Efficacy Period | 0 Participants |
| Vadadustat 300 mg | Number of Participants Who Required Rescue With Erythropoiesis-stimulating Agents (ESAs) From Baseline to the End of the Primary Efficacy Period | 0 Participants |
| Vadadustat 600 mg | Number of Participants Who Required Rescue With Erythropoiesis-stimulating Agents (ESAs) From Baseline to the End of the Primary Efficacy Period | 0 Participants |
| Placebo | Number of Participants Who Required Rescue With Erythropoiesis-stimulating Agents (ESAs) From Baseline to the End of the Primary Efficacy Period | 0 Participants |
Secondary
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
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat 150 | Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 Participants |
| Vadadustat 300 mg | Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period | 2 Participants |
| Vadadustat 600 mg | Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period | 1 Participants |
| Placebo | Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 Participants |
| Placebo to Vadadustat 300 mg | Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 Participants |
| Placebo to Vadadustat 600 mg | Number of Participants Who Required Rescue With ESAs From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat 150 | Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | Treatment-emergent SAEs | 0 Participants |
| Vadadustat 150 | Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | TEAEs | 9 Participants |
| Vadadustat 300 mg | Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | Treatment-emergent SAEs | 5 Participants |
| Vadadustat 300 mg | Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | TEAEs | 10 Participants |
| Vadadustat 600 mg | Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | TEAEs | 6 Participants |
| Vadadustat 600 mg | Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | Treatment-emergent SAEs | 2 Participants |
| Placebo | Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | TEAEs | 3 Participants |
| Placebo | Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | Treatment-emergent SAEs | 1 Participants |
| Placebo to Vadadustat 300 mg | Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | TEAEs | 3 Participants |
| Placebo to Vadadustat 300 mg | Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | Treatment-emergent SAEs | 1 Participants |
| Placebo to Vadadustat 600 mg | Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | Treatment-emergent SAEs | 2 Participants |
| Placebo to Vadadustat 600 mg | Number of Participants With TEAEs and Treatment-emergent SAEs in the Dose Adjustment and Maintenance Period | TEAEs | 3 Participants |
Secondary
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
Population: Safety Population: all enrolled participants who received at least 1 dose of study medication. The Safety Population was based on the actual treatment that participants received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat 150 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period | TEAEs | 4 Participants |
| Vadadustat 150 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period | Treatment-emergent SAEs | 0 Participants |
| Vadadustat 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period | Treatment-emergent SAEs | 0 Participants |
| Vadadustat 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period | TEAEs | 7 Participants |
| Vadadustat 600 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period | TEAEs | 7 Participants |
| Vadadustat 600 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period | Treatment-emergent SAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period | TEAEs | 5 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) in the Primary Efficacy Period | Treatment-emergent SAEs | 0 Participants |
Secondary
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: Baseline to Week 16
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat 150 | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 dose adjustments | 3 Participants |
| Vadadustat 150 | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 1 dose adjustment | 5 Participants |
| Vadadustat 150 | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 2 dose adjustments | 3 Participants |
| Vadadustat 150 | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 3 or more dose adjustments | 1 Participants |
| Vadadustat 300 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 2 dose adjustments | 4 Participants |
| Vadadustat 300 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 1 dose adjustment | 7 Participants |
| Vadadustat 300 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 dose adjustments | 1 Participants |
| Vadadustat 300 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 3 or more dose adjustments | 0 Participants |
| Vadadustat 600 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 3 or more dose adjustments | 7 Participants |
| Vadadustat 600 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 2 dose adjustments | 3 Participants |
| Vadadustat 600 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 1 dose adjustment | 1 Participants |
| Vadadustat 600 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 dose adjustments | 2 Participants |
| Placebo | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 dose adjustments | 0 Participants |
| Placebo | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 3 or more dose adjustments | 1 Participants |
| Placebo | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 1 dose adjustment | 3 Participants |
| Placebo | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 2 dose adjustments | 1 Participants |
| Placebo to Vadadustat 300 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 2 dose adjustments | 1 Participants |
| Placebo to Vadadustat 300 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 3 or more dose adjustments | 2 Participants |
| Placebo to Vadadustat 300 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 1 dose adjustment | 1 Participants |
| Placebo to Vadadustat 300 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 dose adjustments | 0 Participants |
| Placebo to Vadadustat 600 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 1 dose adjustment | 1 Participants |
| Placebo to Vadadustat 600 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 2 dose adjustments | 2 Participants |
| Placebo to Vadadustat 600 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 3 or more dose adjustments | 1 Participants |
| Placebo to Vadadustat 600 mg | Number of the Participants With the Indicated Number of Dose Adjustments From Baseline to the End of the Dose Adjustment and Maintenance Period | 0 dose adjustments | 1 Participants |
Secondary
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
Population: Pharmacokinetic (PK) Population: all participants in the Safety Population (all enrolled participants who received at least 1 dose of study medication) who had a pre-dose PK sample at Week 4.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 150 | Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4 | O-glucuronide | 3914.7 micrograms per milliliter (µg/mL) | Standard Deviation 5772.39 |
| Vadadustat 150 | Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4 | Vadadustat | 5530.9 micrograms per milliliter (µg/mL) | Standard Deviation 4168.86 |
| Vadadustat 150 | Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4 | Acyl-glucuronide | 0.00 micrograms per milliliter (µg/mL) | Standard Deviation 0 |
| Vadadustat 300 mg | Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4 | O-glucuronide | 12358.6 micrograms per milliliter (µg/mL) | Standard Deviation 7586.73 |
| Vadadustat 300 mg | Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4 | Vadadustat | 12955.8 micrograms per milliliter (µg/mL) | Standard Deviation 9771.65 |
| Vadadustat 300 mg | Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4 | Acyl-glucuronide | 1.95 micrograms per milliliter (µg/mL) | Standard Deviation 6.755 |
| Vadadustat 600 mg | Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4 | Vadadustat | 19291.5 micrograms per milliliter (µg/mL) | Standard Deviation 9325.3 |
| Vadadustat 600 mg | Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4 | Acyl-glucuronide | 8.99 micrograms per milliliter (µg/mL) | Standard Deviation 16.43 |
| Vadadustat 600 mg | Plasma Concentration Profile of Vadadustat and Its Metabolites Using a Pre-dose Sample From Week 4 | O-glucuronide | 16586.2 micrograms per milliliter (µg/mL) | Standard Deviation 12363.44 |
Secondary
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
Population: mITT Population. Only participants with Hb \< 10.0 g/dL at the Baseline visit were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vadadustat 150 | Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16 | 56.8 days | Standard Deviation 43.31 |
| Vadadustat 300 mg | Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16 | 39.0 days | Standard Deviation 38.52 |
| Vadadustat 600 mg | Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16 | 25.6 days | Standard Deviation 16.47 |
| Placebo | Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16 | 79.0 days | Standard Deviation 11.31 |
| Placebo to Vadadustat 300 mg | Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16 | 71.0 days | Standard Deviation 14 |
| Placebo to Vadadustat 600 mg | Time to Reach the Target Hb Level of 10.0 to 12.0 g/dL From Baseline up to Week 16 | 54.5 days | Standard Deviation 33.67 |