Anemia, End Stage Renal Disease
Conditions
Keywords
anemia, end stage renal disease, chronic kidney disease, CKD, dialysis, chronic renal insufficiency, renal impairment, erythropoietin, kidney, oral anemia treatment, hemoglobin, hypoxia-inducible factor, HIF, hypoxia-inducible factor propyl-hydroxylase inhibitor, HIF-PHI, pharmacokinetics
Brief summary
The purpose of this study is to evaluate the hemoglobin response (efficacy), safety, and tolerability of orally administered AKB-6548 in participants with end stage renal disease undergoing chronic hemodialysis.
Interventions
DRUGAKB-6548
Starting dose 1. Oral dose administered once daily for 16 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.
Sponsors
Akebia Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 18 to 79 years inclusive * Chronic Kidney Disease (CKD) Stage 5 on chronic hemodialysis for at least 3 months * Anemia secondary to CKD treated with erythropoiesis stimulating agent and intravenous iron Key
Exclusion criteria
* Body mass index \>44.0 kilograms per meter squared (kg/m\^2) * Transfusion within 8 weeks prior to Screening * Alanine transaminase or total bilirubin \>1.25x ULN * Uncontrolled hypertension * Class III or IV congestive heart failure * Myocardial infarction, acute coronary syndrome, stroke or transient ischemic attack within 6 months prior to Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Mid-study Average in Hgb Level to The End-of-study Average | Week 7, Week 8, Week 15, and Week 16 | Change from mid-study average was calculated by the end-of-study average minus the mid-study average. The mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits. |
| Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average | Pre-dose (Screening, Second Screening, and Baseline), Week 7, and Week 8 | Change from pre-dose average was calculated by the mid-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits. |
| Change From Pre-dose Average in Hgb Level to The End-of-study Average | Pre-dose, Week 15, and Week 16 | Change from pre-dose average was calculated by the end-of-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Red Blood Cell (RBC) Count | Baseline, Week 4, Week 8, Week 12, and Week 16 | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline RBC Count was defined as the average of the three samples obtained prior to dosing. |
| Change From Baseline in Absolute Reticulocyte Count | Baseline, Week 4, Week 8, Week 12, and Week 16 | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline absolute reticulocyte count was defined as the last observation before the first dose of study medication. |
| Change From Baseline in Percent Reticulocyte Count | Baseline, Week 4, Week 8, Week 12, and Week 16 | Change from Baseline was calculated as (visit value minus the Baseline value)/ Baseline value x 100. Baseline percent reticulocyte count was defined as the last observation before the first dose of study medication. |
| Change From Baseline in Reticulocyte Hgb Content | Baseline, Week 2, Week 4, Week 8, and Week 16 | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline reticulocyte Hgb content was defined as the average of the three samples obtained prior to dosing. |
| Change From Baseline in Ferritin | Baseline, Week 4, Week 8, Week 12, and Week 16 | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline ferritin was defined as the last observation before the first dose of study medication. |
| Change From Baseline in Hepcidin | Baseline, Week 8, and Week 16 | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline hepcidin was defined as the last observation before the first dose of study medication. |
| Change From Baseline in Total Iron-Binding Capacity (TIBC) | Baseline, Week 4, Week 8, Week 12, and Week 16 | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline TIBC was defined as the last observation before the first dose of study medication. |
| Change From Baseline in Transferrin Saturation (TSAT) | Baseline, Week 4, Week 8, Week 12, and Week 16 | Change from Baseline was calculated as (visit value minus the Baseline value)/ Baseline value x 100. Baseline TSAT was defined as the last observation before the first dose of study medication. |
| Change From Baseline in Iron | Baseline, Week 4, Week 8, Week 12, and Week 16 | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline iron was defined as the last observation before the first dose of study medication. |
| Number of Participants Who Received Blood Transfusion Rescue Therapy | Up to Week 16 | Blood transfusion rescue therapy was administered in participants with Hgb ≤12.5 g/dL, and was stopped when Hgb reached ≥13.0 g/dL. |
| Mean Plasma Concentrations of Vadadustat | Pre-dialysis and post-dialysis on Week 2 and Week 16 | Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session. |
| Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Pre-dialysis and post-dialysis on Week 2 and Week 16 | Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session. |
| Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite | Pre-dialysis and post-dialysis on Week 2 and Week 16 | Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session. |
| Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to Week 20 | 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. A TEAE 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. A SAE included AEs that met one or more of the following criteria/outcomes: death, lifethreatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, and congenital anomaly/birth defect. |
| Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | Up to Week 20 | Parameters assessed for vital signs included sitting blood pressure, pulse, respiratory rate, and body temperature. The investigator was responsible for reviewing laboratory results for clinically significant changes. |
| Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | Up to Week 20 | Parameters assessed for laboratory values included hematology, serum chemistry, urinalysis, iron indices, C-reactive protein, lipid profile, biomarkers, and pregnancy tests. The investigator was responsible for reviewing laboratory results for clinically significant changes. |
| Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings | Up to Week 20 | A standard 12-lead ECG was performed following dosing in a supine position for approximately 5 minutes. ECGs were taken prior to vital sign assessments, circulatory access cannulation, and blood draws when possible. Clinical significance was determined by the investigator. |
| Number of Participants Who Received Erythropoiesis-stimulating Agent (ESA) Rescue Therapy | Up to Week 16 | ESA rescue therapy was administered in participants with Hgb ≤12.5 g/dL, and was stopped when Hgb reached ≥13.0 g/dL. |
| Change From Baseline in Hgb | Baseline, Week 4, Week 8, Week 12, and Week 16 | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hgb was defined as the average of the three samples obtained prior to dosing. |
| Change From Baseline in Hematocrit | Baseline, Week 4, Week 8, Week 12, and Week 16 | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hematocrit was defined as the last observation before the first dose of study medication. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Intravenous Iron Replacement Therapy | Baseline, Week 8, and Week 16 | Intravenous iron was administered throughout the study to maintain ferritin levels in the range of ≥100 ng/mL to ≤1200 ng/mL. |
Countries
United States
Participant flow
Pre-assignment details
A total of 128 participants were screened, of which 94 participants were enrolled and randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Vadadustat 300 mg Once Daily (QD) Participants received a starting dose of Vadadustat 300 milligrams (mg) QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in hemoglobin (Hgb) levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed. | 30 |
| Vadadustat 450 mg QD Participants received a starting dose of Vadadustat 450 mg QD orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed. | 33 |
| Vadadustat 450 mg 3 Times Per Week (TIW) Participants received a starting dose of Vadadustat 450 mg TIW orally for 8 weeks. Dose increases (up to a maximum of 600 mg) were allowed once every 4 weeks after the initial 8 weeks of treatment up to Week 12, based on the changes in Hgb levels for the participant. Dose of Vadadustat were reduced at any time during the 16-week treatment period, if intolerance or an excessive increase in Hgb level (Hgb level ≥13.0 g/dL) was observed. | 31 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 | 1 |
| Overall Study | Kidney Transplantation | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 | 6 |
| Overall Study | Protocol Violation | 0 | 4 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 2 |
Baseline characteristics
| Characteristic | Vadadustat 300 mg Once Daily (QD) | Vadadustat 450 mg QD | Vadadustat 450 mg 3 Times Per Week (TIW) | Total |
|---|---|---|---|---|
| Age, Continuous | 55.5 Years STANDARD_DEVIATION 12.44 | 59.4 Years STANDARD_DEVIATION 11.62 | 57.8 Years STANDARD_DEVIATION 8.26 | 57.6 Years STANDARD_DEVIATION 10.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 18 Participants | 15 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 15 Participants | 16 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 9 Participants | 9 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 21 Participants | 19 Participants | 64 Participants |
| Sex: Female, Male Female | 13 Participants | 15 Participants | 12 Participants | 40 Participants |
| Sex: Female, Male Male | 17 Participants | 18 Participants | 19 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 33 | 0 / 31 |
| other Total, other adverse events | 22 / 30 | 19 / 33 | 23 / 31 |
| serious Total, serious adverse events | 5 / 30 | 9 / 33 | 8 / 31 |
Outcome results
Primary
Change From Mid-study Average in Hgb Level to The End-of-study Average
Change from mid-study average was calculated by the end-of-study average minus the mid-study average. The mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits.
Time frame: Week 7, Week 8, Week 15, and Week 16
Population: MITT Population. The primary analysis was performed in the MITT population using observed Hgb data without imputation for missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Mid-study Average in Hgb Level to The End-of-study Average | Mid-study Average | 10.41 g/dL | Standard Deviation 0.834 |
| Vadadustat 300 mg Once Daily (QD) | Change From Mid-study Average in Hgb Level to The End-of-study Average | Change From Mid-study Average to The End-of-study Average | -0.18 g/dL | Standard Deviation 0.512 |
| Vadadustat 450 mg QD | Change From Mid-study Average in Hgb Level to The End-of-study Average | Mid-study Average | 10.26 g/dL | Standard Deviation 1.167 |
| Vadadustat 450 mg QD | Change From Mid-study Average in Hgb Level to The End-of-study Average | Change From Mid-study Average to The End-of-study Average | 0.16 g/dL | Standard Deviation 0.809 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Mid-study Average in Hgb Level to The End-of-study Average | Mid-study Average | 10.19 g/dL | Standard Deviation 0.95 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Mid-study Average in Hgb Level to The End-of-study Average | Change From Mid-study Average to The End-of-study Average | -0.07 g/dL | Standard Deviation 0.611 |
95% CI: [-0.71, 0.04]
95% CI: [-0.5, 0.29]
95% CI: [-0.16, 0.62]
Primary
Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average
Change from pre-dose average was calculated by the mid-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits.
Time frame: Pre-dose (Screening, Second Screening, and Baseline), Week 7, and Week 8
Population: Modified Intent-to-treat (MITT) Population: All participants who were assigned to study medication, received at least 1 dose of study medication, and had a pre-dose average and at least one post-baseline Hgb measurement. The primary analysis was performed in the MITT population using observed Hgb data without imputation for missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average | Change from pre-dose average to the mid-study average | 0.00 Grams per deciliter (g/dL) | Standard Deviation 0.897 |
| Vadadustat 300 mg Once Daily (QD) | Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average | Pre-dose Average | 10.43 Grams per deciliter (g/dL) | Standard Deviation 0.645 |
| Vadadustat 450 mg QD | Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average | Change from pre-dose average to the mid-study average | -0.29 Grams per deciliter (g/dL) | Standard Deviation 0.97 |
| Vadadustat 450 mg QD | Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average | Pre-dose Average | 10.55 Grams per deciliter (g/dL) | Standard Deviation 0.577 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average | Change from pre-dose average to the mid-study average | -0.36 Grams per deciliter (g/dL) | Standard Deviation 1.134 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average | Pre-dose Average | 10.52 Grams per deciliter (g/dL) | Standard Deviation 0.534 |
95% CI: [-0.25, 0.82]
95% CI: [-0.19, 0.9]
95% CI: [-0.48, 0.61]
Primary
Change From Pre-dose Average in Hgb Level to The End-of-study Average
Change from pre-dose average was calculated by the end-of-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits.
Time frame: Pre-dose, Week 15, and Week 16
Population: MITT Population. The primary analysis was performed in the MITT population using observed Hgb data without imputation for missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Pre-dose Average in Hgb Level to The End-of-study Average | Pre-dose Average | 10.43 g/dL | Standard Deviation 0.645 |
| Vadadustat 300 mg Once Daily (QD) | Change From Pre-dose Average in Hgb Level to The End-of-study Average | Change From Pre-dose average to The End-of-study Average | -0.03 g/dL | Standard Deviation 0.902 |
| Vadadustat 450 mg QD | Change From Pre-dose Average in Hgb Level to The End-of-study Average | Pre-dose Average | 10.55 g/dL | Standard Deviation 0.577 |
| Vadadustat 450 mg QD | Change From Pre-dose Average in Hgb Level to The End-of-study Average | Change From Pre-dose average to The End-of-study Average | -0.07 g/dL | Standard Deviation 0.973 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Pre-dose Average in Hgb Level to The End-of-study Average | Pre-dose Average | 10.52 g/dL | Standard Deviation 0.534 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Pre-dose Average in Hgb Level to The End-of-study Average | Change From Pre-dose average to The End-of-study Average | -0.14 g/dL | Standard Deviation 1.123 |
95% CI: [-0.54, 0.61]
95% CI: [-0.49, 0.7]
95% CI: [-0.53, 0.66]
Secondary
Change From Baseline in Absolute Reticulocyte Count
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline absolute reticulocyte count was defined as the last observation before the first dose of study medication.
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Population: MITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Absolute Reticulocyte Count | Baseline | 0.0704 10^6 cells per microliter | Standard Deviation 0.02548 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Absolute Reticulocyte Count | Change from Baseline to Week 12 | 0.0001 10^6 cells per microliter | Standard Deviation 0.01592 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Absolute Reticulocyte Count | Change from Baseline to Week 8 | -0.0054 10^6 cells per microliter | Standard Deviation 0.01794 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Absolute Reticulocyte Count | Change from Baseline to Week 16 | -0.0009 10^6 cells per microliter | Standard Deviation 0.02251 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Absolute Reticulocyte Count | Change from Baseline to Week 4 | -0.0059 10^6 cells per microliter | Standard Deviation 0.02166 |
| Vadadustat 450 mg QD | Change From Baseline in Absolute Reticulocyte Count | Change from Baseline to Week 16 | 0.0048 10^6 cells per microliter | Standard Deviation 0.02409 |
| Vadadustat 450 mg QD | Change From Baseline in Absolute Reticulocyte Count | Baseline | 0.0661 10^6 cells per microliter | Standard Deviation 0.023 |
| Vadadustat 450 mg QD | Change From Baseline in Absolute Reticulocyte Count | Change from Baseline to Week 4 | 0.0023 10^6 cells per microliter | Standard Deviation 0.02597 |
| Vadadustat 450 mg QD | Change From Baseline in Absolute Reticulocyte Count | Change from Baseline to Week 8 | 0.0041 10^6 cells per microliter | Standard Deviation 0.02492 |
| Vadadustat 450 mg QD | Change From Baseline in Absolute Reticulocyte Count | Change from Baseline to Week 12 | 0.0133 10^6 cells per microliter | Standard Deviation 0.02734 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Absolute Reticulocyte Count | Change from Baseline to Week 4 | -0.0001 10^6 cells per microliter | Standard Deviation 0.02813 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Absolute Reticulocyte Count | Change from Baseline to Week 16 | 0.0040 10^6 cells per microliter | Standard Deviation 0.0247 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Absolute Reticulocyte Count | Change from Baseline to Week 12 | 0.0033 10^6 cells per microliter | Standard Deviation 0.02479 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Absolute Reticulocyte Count | Baseline | 0.0742 10^6 cells per microliter | Standard Deviation 0.02777 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Absolute Reticulocyte Count | Change from Baseline to Week 8 | -0.0018 10^6 cells per microliter | Standard Deviation 0.02571 |
Secondary
Change From Baseline in Ferritin
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline ferritin was defined as the last observation before the first dose of study medication.
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Population: MITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Ferritin | Change from Baseline to Week 12 | -15.70 Nanograms per milliliter (ng/mL) | Standard Deviation 316.387 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Ferritin | Baseline | 762.88 Nanograms per milliliter (ng/mL) | Standard Deviation 470.462 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Ferritin | Change from Baseline to Week 8 | 46.85 Nanograms per milliliter (ng/mL) | Standard Deviation 529.361 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Ferritin | Change from Baseline to Week 16 | -56.67 Nanograms per milliliter (ng/mL) | Standard Deviation 317.098 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Ferritin | Change from Baseline to Week 4 | -48.80 Nanograms per milliliter (ng/mL) | Standard Deviation 205.733 |
| Vadadustat 450 mg QD | Change From Baseline in Ferritin | Change from Baseline to Week 16 | -115.36 Nanograms per milliliter (ng/mL) | Standard Deviation 276.64 |
| Vadadustat 450 mg QD | Change From Baseline in Ferritin | Baseline | 781.96 Nanograms per milliliter (ng/mL) | Standard Deviation 465.148 |
| Vadadustat 450 mg QD | Change From Baseline in Ferritin | Change from Baseline to Week 4 | -61.21 Nanograms per milliliter (ng/mL) | Standard Deviation 217.068 |
| Vadadustat 450 mg QD | Change From Baseline in Ferritin | Change from Baseline to Week 12 | -61.81 Nanograms per milliliter (ng/mL) | Standard Deviation 302.719 |
| Vadadustat 450 mg QD | Change From Baseline in Ferritin | Change from Baseline to Week 8 | -99.11 Nanograms per milliliter (ng/mL) | Standard Deviation 240.436 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Ferritin | Change from Baseline to Week 12 | 0.92 Nanograms per milliliter (ng/mL) | Standard Deviation 342.188 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Ferritin | Change from Baseline to Week 8 | -48.71 Nanograms per milliliter (ng/mL) | Standard Deviation 289.063 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Ferritin | Change from Baseline to Week 4 | -10.29 Nanograms per milliliter (ng/mL) | Standard Deviation 254.574 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Ferritin | Change from Baseline to Week 16 | -39.03 Nanograms per milliliter (ng/mL) | Standard Deviation 484.937 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Ferritin | Baseline | 807.75 Nanograms per milliliter (ng/mL) | Standard Deviation 430.981 |
Secondary
Change From Baseline in Hematocrit
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hematocrit was defined as the last observation before the first dose of study medication.
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Population: MITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hematocrit | Change from Baseline to Week 12 | -0.2 Percentage of red blood cells in blood | Standard Deviation 3.35 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hematocrit | Change from Baseline to Week 8 | -1.0 Percentage of red blood cells in blood | Standard Deviation 3.87 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hematocrit | Baseline | 31.2 Percentage of red blood cells in blood | Standard Deviation 2.58 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hematocrit | Change from Baseline to Week 4 | -0.4 Percentage of red blood cells in blood | Standard Deviation 2.82 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hematocrit | Change from Baseline to Week 16 | -0.8 Percentage of red blood cells in blood | Standard Deviation 3.26 |
| Vadadustat 450 mg QD | Change From Baseline in Hematocrit | Change from Baseline to Week 8 | -1.6 Percentage of red blood cells in blood | Standard Deviation 4.73 |
| Vadadustat 450 mg QD | Change From Baseline in Hematocrit | Baseline | 31.6 Percentage of red blood cells in blood | Standard Deviation 3.75 |
| Vadadustat 450 mg QD | Change From Baseline in Hematocrit | Change from Baseline to Week 4 | -1.4 Percentage of red blood cells in blood | Standard Deviation 3.36 |
| Vadadustat 450 mg QD | Change From Baseline in Hematocrit | Change from Baseline to Week 12 | -0.8 Percentage of red blood cells in blood | Standard Deviation 4.07 |
| Vadadustat 450 mg QD | Change From Baseline in Hematocrit | Change from Baseline to Week 16 | -1.2 Percentage of red blood cells in blood | Standard Deviation 4.19 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hematocrit | Change from Baseline to Week 16 | -0.2 Percentage of red blood cells in blood | Standard Deviation 3.67 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hematocrit | Change from Baseline to Week 12 | -0.1 Percentage of red blood cells in blood | Standard Deviation 4.35 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hematocrit | Baseline | 31.4 Percentage of red blood cells in blood | Standard Deviation 2.75 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hematocrit | Change from Baseline to Week 8 | -1.7 Percentage of red blood cells in blood | Standard Deviation 4.43 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hematocrit | Change from Baseline to Week 4 | -0.7 Percentage of red blood cells in blood | Standard Deviation 3.14 |
Secondary
Change From Baseline in Hepcidin
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline hepcidin was defined as the last observation before the first dose of study medication.
Time frame: Baseline, Week 8, and Week 16
Population: MITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hepcidin | Change from Baseline to Week 8 | -6.46 Nanograms per milliliter (ng/mL) | Standard Deviation 49.002 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hepcidin | Baseline | 102.59 Nanograms per milliliter (ng/mL) | Standard Deviation 58.938 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hepcidin | Change from Baseline to Week 16 | -15.11 Nanograms per milliliter (ng/mL) | Standard Deviation 46.526 |
| Vadadustat 450 mg QD | Change From Baseline in Hepcidin | Change from Baseline to Week 8 | -27.80 Nanograms per milliliter (ng/mL) | Standard Deviation 56.752 |
| Vadadustat 450 mg QD | Change From Baseline in Hepcidin | Baseline | 119.61 Nanograms per milliliter (ng/mL) | Standard Deviation 54.766 |
| Vadadustat 450 mg QD | Change From Baseline in Hepcidin | Change from Baseline to Week 16 | -21.66 Nanograms per milliliter (ng/mL) | Standard Deviation 45.381 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hepcidin | Baseline | 105.35 Nanograms per milliliter (ng/mL) | Standard Deviation 46.805 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hepcidin | Change from Baseline to Week 16 | -4.87 Nanograms per milliliter (ng/mL) | Standard Deviation 50.379 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hepcidin | Change from Baseline to Week 8 | -9.14 Nanograms per milliliter (ng/mL) | Standard Deviation 46.498 |
Secondary
Change From Baseline in Hgb
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hgb was defined as the average of the three samples obtained prior to dosing.
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Population: MITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hgb | Change from Baseline to Week 12 | 0.02 g/dL | Standard Deviation 0.995 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hgb | Change from Baseline to Week 16 | -0.03 g/dL | Standard Deviation 0.946 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hgb | Change from Baseline to Week 4 | -0.06 g/dL | Standard Deviation 0.708 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hgb | Change from Baseline to Week 8 | -0.14 g/dL | Standard Deviation 1.058 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Hgb | Baseline | 10.50 g/dL | Standard Deviation 0.702 |
| Vadadustat 450 mg QD | Change From Baseline in Hgb | Change from Baseline to Week 8 | -0.39 g/dL | Standard Deviation 1.201 |
| Vadadustat 450 mg QD | Change From Baseline in Hgb | Baseline | 10.51 g/dL | Standard Deviation 0.755 |
| Vadadustat 450 mg QD | Change From Baseline in Hgb | Change from Baseline to Week 12 | -0.11 g/dL | Standard Deviation 1.087 |
| Vadadustat 450 mg QD | Change From Baseline in Hgb | Change from Baseline to Week 16 | -0.13 g/dL | Standard Deviation 1.076 |
| Vadadustat 450 mg QD | Change From Baseline in Hgb | Change from Baseline to Week 4 | -0.21 g/dL | Standard Deviation 0.814 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hgb | Change from Baseline to Week 16 | -0.06 g/dL | Standard Deviation 1.146 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hgb | Change from Baseline to Week 4 | -0.35 g/dL | Standard Deviation 0.887 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hgb | Change from Baseline to Week 8 | -0.37 g/dL | Standard Deviation 1.386 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hgb | Change from Baseline to Week 12 | -0.06 g/dL | Standard Deviation 1.21 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Hgb | Baseline | 10.50 g/dL | Standard Deviation 0.646 |
Secondary
Change From Baseline in Iron
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline iron was defined as the last observation before the first dose of study medication.
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Population: MITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Iron | Change from Baseline to Week 4 | 20.7 μg/dL | Standard Deviation 32.47 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Iron | Change from Baseline to Week 8 | 14.3 μg/dL | Standard Deviation 33.38 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Iron | Change from Baseline to Week 12 | 31.7 μg/dL | Standard Deviation 46.73 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Iron | Baseline | 70.6 μg/dL | Standard Deviation 26.25 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Iron | Change from Baseline to Week 16 | 14.0 μg/dL | Standard Deviation 34.43 |
| Vadadustat 450 mg QD | Change From Baseline in Iron | Change from Baseline to Week 8 | 11.6 μg/dL | Standard Deviation 39.1 |
| Vadadustat 450 mg QD | Change From Baseline in Iron | Change from Baseline to Week 16 | 10.3 μg/dL | Standard Deviation 37.16 |
| Vadadustat 450 mg QD | Change From Baseline in Iron | Baseline | 66.6 μg/dL | Standard Deviation 23.74 |
| Vadadustat 450 mg QD | Change From Baseline in Iron | Change from Baseline to Week 12 | 10.8 μg/dL | Standard Deviation 31.44 |
| Vadadustat 450 mg QD | Change From Baseline in Iron | Change from Baseline to Week 4 | 18.5 μg/dL | Standard Deviation 40.91 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Iron | Change from Baseline to Week 12 | 15.5 μg/dL | Standard Deviation 28.01 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Iron | Change from Baseline to Week 16 | 14.0 μg/dL | Standard Deviation 28.62 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Iron | Change from Baseline to Week 8 | 15.0 μg/dL | Standard Deviation 30.22 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Iron | Change from Baseline to Week 4 | 13.3 μg/dL | Standard Deviation 30.06 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Iron | Baseline | 75.4 μg/dL | Standard Deviation 32.31 |
Secondary
Change From Baseline in Percent Reticulocyte Count
Change from Baseline was calculated as (visit value minus the Baseline value)/ Baseline value x 100. Baseline percent reticulocyte count was defined as the last observation before the first dose of study medication.
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Population: MITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Percent Reticulocyte Count | Change from Baseline to Week 8 | -0.15 Percent change | Standard Deviation 0.539 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Percent Reticulocyte Count | Change from Baseline to Week 4 | -0.16 Percent change | Standard Deviation 0.578 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Percent Reticulocyte Count | Baseline | 2.14 Percent change | Standard Deviation 0.802 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Percent Reticulocyte Count | Change from Baseline to Week 12 | -0.04 Percent change | Standard Deviation 0.488 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Percent Reticulocyte Count | Change from Baseline to Week 16 | -0.01 Percent change | Standard Deviation 0.586 |
| Vadadustat 450 mg QD | Change From Baseline in Percent Reticulocyte Count | Change from Baseline to Week 4 | 0.14 Percent change | Standard Deviation 0.787 |
| Vadadustat 450 mg QD | Change From Baseline in Percent Reticulocyte Count | Change from Baseline to Week 16 | 0.23 Percent change | Standard Deviation 0.701 |
| Vadadustat 450 mg QD | Change From Baseline in Percent Reticulocyte Count | Baseline | 1.89 Percent change | Standard Deviation 0.572 |
| Vadadustat 450 mg QD | Change From Baseline in Percent Reticulocyte Count | Change from Baseline to Week 8 | 0.24 Percent change | Standard Deviation 0.649 |
| Vadadustat 450 mg QD | Change From Baseline in Percent Reticulocyte Count | Change from Baseline to Week 12 | 0.48 Percent change | Standard Deviation 0.704 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Percent Reticulocyte Count | Change from Baseline to Week 12 | 0.17 Percent change | Standard Deviation 0.835 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Percent Reticulocyte Count | Change from Baseline to Week 8 | 0.03 Percent change | Standard Deviation 0.71 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Percent Reticulocyte Count | Change from Baseline to Week 16 | 0.15 Percent change | Standard Deviation 0.817 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Percent Reticulocyte Count | Change from Baseline to Week 4 | 0.07 Percent change | Standard Deviation 0.884 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Percent Reticulocyte Count | Baseline | 2.19 Percent change | Standard Deviation 0.927 |
Secondary
Change From Baseline in Red Blood Cell (RBC) Count
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline RBC Count was defined as the average of the three samples obtained prior to dosing.
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Population: MITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Red Blood Cell (RBC) Count | Change from Baseline to Week 12 | -0.01 10^6 cells per microliter | Standard Deviation 0.325 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Red Blood Cell (RBC) Count | Baseline | 3.34 10^6 cells per microliter | Standard Deviation 0.278 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Red Blood Cell (RBC) Count | Change from Baseline to Week 16 | -0.05 10^6 cells per microliter | Standard Deviation 0.309 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Red Blood Cell (RBC) Count | Change from Baseline to Week 4 | -0.06 10^6 cells per microliter | Standard Deviation 0.235 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Red Blood Cell (RBC) Count | Change from Baseline to Week 8 | -0.09 10^6 cells per microliter | Standard Deviation 0.357 |
| Vadadustat 450 mg QD | Change From Baseline in Red Blood Cell (RBC) Count | Change from Baseline to Week 12 | -0.14 10^6 cells per microliter | Standard Deviation 0.473 |
| Vadadustat 450 mg QD | Change From Baseline in Red Blood Cell (RBC) Count | Change from Baseline to Week 4 | -0.11 10^6 cells per microliter | Standard Deviation 0.346 |
| Vadadustat 450 mg QD | Change From Baseline in Red Blood Cell (RBC) Count | Baseline | 3.49 10^6 cells per microliter | Standard Deviation 0.446 |
| Vadadustat 450 mg QD | Change From Baseline in Red Blood Cell (RBC) Count | Change from Baseline to Week 16 | -0.17 10^6 cells per microliter | Standard Deviation 0.453 |
| Vadadustat 450 mg QD | Change From Baseline in Red Blood Cell (RBC) Count | Change from Baseline to Week 8 | -0.19 10^6 cells per microliter | Standard Deviation 0.482 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Red Blood Cell (RBC) Count | Change from Baseline to Week 16 | -0.08 10^6 cells per microliter | Standard Deviation 0.412 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Red Blood Cell (RBC) Count | Change from Baseline to Week 8 | -0.16 10^6 cells per microliter | Standard Deviation 0.432 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Red Blood Cell (RBC) Count | Baseline | 3.49 10^6 cells per microliter | Standard Deviation 0.385 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Red Blood Cell (RBC) Count | Change from Baseline to Week 4 | -0.16 10^6 cells per microliter | Standard Deviation 0.276 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Red Blood Cell (RBC) Count | Change from Baseline to Week 12 | -0.10 10^6 cells per microliter | Standard Deviation 0.464 |
Secondary
Change From Baseline in Reticulocyte Hgb Content
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline reticulocyte Hgb content was defined as the average of the three samples obtained prior to dosing.
Time frame: Baseline, Week 2, Week 4, Week 8, and Week 16
Population: MITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Reticulocyte Hgb Content | Baseline | 32.39 μg/dL | Standard Deviation 1.799 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Reticulocyte Hgb Content | Change from Baseline to Week 8 | 0.41 μg/dL | Standard Deviation 1.159 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Reticulocyte Hgb Content | Change from Baseline to Week 16 | 0.15 μg/dL | Standard Deviation 1.026 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Reticulocyte Hgb Content | Change from Baseline to Week 2 | -0.13 μg/dL | Standard Deviation 1.302 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Reticulocyte Hgb Content | Change from Baseline to Week 4 | -0.07 μg/dL | Standard Deviation 0.859 |
| Vadadustat 450 mg QD | Change From Baseline in Reticulocyte Hgb Content | Change from Baseline to Week 2 | -0.03 μg/dL | Standard Deviation 0.972 |
| Vadadustat 450 mg QD | Change From Baseline in Reticulocyte Hgb Content | Baseline | 32.12 μg/dL | Standard Deviation 1.675 |
| Vadadustat 450 mg QD | Change From Baseline in Reticulocyte Hgb Content | Change from Baseline to Week 4 | -0.21 μg/dL | Standard Deviation 1.023 |
| Vadadustat 450 mg QD | Change From Baseline in Reticulocyte Hgb Content | Change from Baseline to Week 8 | -0.27 μg/dL | Standard Deviation 1.308 |
| Vadadustat 450 mg QD | Change From Baseline in Reticulocyte Hgb Content | Change from Baseline to Week 16 | 0.58 μg/dL | Standard Deviation 1.284 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Reticulocyte Hgb Content | Change from Baseline to Week 8 | 1.13 μg/dL | Standard Deviation 1.301 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Reticulocyte Hgb Content | Baseline | 30.99 μg/dL | Standard Deviation 2.372 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Reticulocyte Hgb Content | Change from Baseline to Week 2 | 1.01 μg/dL | Standard Deviation 1.621 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Reticulocyte Hgb Content | Change from Baseline to Week 16 | -0.18 μg/dL | Standard Deviation 1.494 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Reticulocyte Hgb Content | Change from Baseline to Week 4 | 1.02 μg/dL | Standard Deviation 1.425 |
Secondary
Change From Baseline in Total Iron-Binding Capacity (TIBC)
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline TIBC was defined as the last observation before the first dose of study medication.
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Population: MITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Change from Baseline to Week 12 | 30.6 Micrograms per deciliter (μg/mL) | Standard Deviation 30.05 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Change from Baseline to Week 8 | 23.4 Micrograms per deciliter (μg/mL) | Standard Deviation 28.13 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Baseline | 204.5 Micrograms per deciliter (μg/mL) | Standard Deviation 39.72 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Change from Baseline to Week 4 | 25.7 Micrograms per deciliter (μg/mL) | Standard Deviation 21.95 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Change from Baseline to Week 16 | 27.7 Micrograms per deciliter (μg/mL) | Standard Deviation 35.27 |
| Vadadustat 450 mg QD | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Baseline | 196.7 Micrograms per deciliter (μg/mL) | Standard Deviation 29.42 |
| Vadadustat 450 mg QD | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Change from Baseline to Week 4 | 22.0 Micrograms per deciliter (μg/mL) | Standard Deviation 32.18 |
| Vadadustat 450 mg QD | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Change from Baseline to Week 8 | 30.3 Micrograms per deciliter (μg/mL) | Standard Deviation 28.3 |
| Vadadustat 450 mg QD | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Change from Baseline to Week 12 | 34.8 Micrograms per deciliter (μg/mL) | Standard Deviation 28.69 |
| Vadadustat 450 mg QD | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Change from Baseline to Week 16 | 24.9 Micrograms per deciliter (μg/mL) | Standard Deviation 29.1 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Change from Baseline to Week 16 | 25.7 Micrograms per deciliter (μg/mL) | Standard Deviation 21.78 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Change from Baseline to Week 12 | 23.9 Micrograms per deciliter (μg/mL) | Standard Deviation 19.62 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Baseline | 188.8 Micrograms per deciliter (μg/mL) | Standard Deviation 32.28 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Change from Baseline to Week 8 | 22.0 Micrograms per deciliter (μg/mL) | Standard Deviation 25.37 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Total Iron-Binding Capacity (TIBC) | Change from Baseline to Week 4 | 18.7 Micrograms per deciliter (μg/mL) | Standard Deviation 22.39 |
Secondary
Change From Baseline in Transferrin Saturation (TSAT)
Change from Baseline was calculated as (visit value minus the Baseline value)/ Baseline value x 100. Baseline TSAT was defined as the last observation before the first dose of study medication.
Time frame: Baseline, Week 4, Week 8, Week 12, and Week 16
Population: MITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Transferrin Saturation (TSAT) | Change from Baseline to Week 12 | 9.1 Percent change | Standard Deviation 19.71 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Transferrin Saturation (TSAT) | Change from Baseline to Week 8 | 2.9 Percent change | Standard Deviation 15.92 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Transferrin Saturation (TSAT) | Baseline | 34.6 Percent change | Standard Deviation 11.63 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Transferrin Saturation (TSAT) | Change from Baseline to Week 4 | 5.4 Percent change | Standard Deviation 15.49 |
| Vadadustat 300 mg Once Daily (QD) | Change From Baseline in Transferrin Saturation (TSAT) | Change from Baseline to Week 16 | 2.5 Percent change | Standard Deviation 14.86 |
| Vadadustat 450 mg QD | Change From Baseline in Transferrin Saturation (TSAT) | Change from Baseline to Week 8 | 1.2 Percent change | Standard Deviation 17.31 |
| Vadadustat 450 mg QD | Change From Baseline in Transferrin Saturation (TSAT) | Baseline | 33.7 Percent change | Standard Deviation 11.14 |
| Vadadustat 450 mg QD | Change From Baseline in Transferrin Saturation (TSAT) | Change from Baseline to Week 4 | 2.1 Percent change | Standard Deviation 16.97 |
| Vadadustat 450 mg QD | Change From Baseline in Transferrin Saturation (TSAT) | Change from Baseline to Week 12 | 1.3 Percent change | Standard Deviation 17.18 |
| Vadadustat 450 mg QD | Change From Baseline in Transferrin Saturation (TSAT) | Change from Baseline to Week 16 | 1.7 Percent change | Standard Deviation 17.44 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Transferrin Saturation (TSAT) | Change from Baseline to Week 16 | 2.5 Percent change | Standard Deviation 13.75 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Transferrin Saturation (TSAT) | Change from Baseline to Week 12 | 3.7 Percent change | Standard Deviation 14.08 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Transferrin Saturation (TSAT) | Baseline | 37.5 Percent change | Standard Deviation 13.27 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Transferrin Saturation (TSAT) | Change from Baseline to Week 8 | 3.3 Percent change | Standard Deviation 14.87 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Change From Baseline in Transferrin Saturation (TSAT) | Change from Baseline to Week 4 | 3.6 Percent change | Standard Deviation 15.84 |
Secondary
Mean Plasma Concentrations of Vadadustat
Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.
Time frame: Pre-dialysis and post-dialysis on Week 2 and Week 16
Population: ITT Population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Mean Plasma Concentrations of Vadadustat | Week 16 post-dialysis | 13.85 μg/mL | Standard Deviation 11.921 |
| Vadadustat 300 mg Once Daily (QD) | Mean Plasma Concentrations of Vadadustat | Week 2 post-dialysis | 13.72 μg/mL | Standard Deviation 13.728 |
| Vadadustat 300 mg Once Daily (QD) | Mean Plasma Concentrations of Vadadustat | Week 16 pre-dialysis | 11.41 μg/mL | Standard Deviation 8.7716 |
| Vadadustat 300 mg Once Daily (QD) | Mean Plasma Concentrations of Vadadustat | Week 2 pre-dialysis | 12.89 μg/mL | Standard Deviation 13.876 |
| Vadadustat 450 mg QD | Mean Plasma Concentrations of Vadadustat | Week 2 post-dialysis | 18.69 μg/mL | Standard Deviation 15.601 |
| Vadadustat 450 mg QD | Mean Plasma Concentrations of Vadadustat | Week 16 pre-dialysis | 15.98 μg/mL | Standard Deviation 12.059 |
| Vadadustat 450 mg QD | Mean Plasma Concentrations of Vadadustat | Week 2 pre-dialysis | 17.27 μg/mL | Standard Deviation 12.741 |
| Vadadustat 450 mg QD | Mean Plasma Concentrations of Vadadustat | Week 16 post-dialysis | 17.38 μg/mL | Standard Deviation 12.516 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Mean Plasma Concentrations of Vadadustat | Week 16 pre-dialysis | 4.813 μg/mL | Standard Deviation 3.6094 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Mean Plasma Concentrations of Vadadustat | Week 2 pre-dialysis | 5.329 μg/mL | Standard Deviation 5.0281 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Mean Plasma Concentrations of Vadadustat | Week 16 post-dialysis | 3.998 μg/mL | Standard Deviation 2.9709 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Mean Plasma Concentrations of Vadadustat | Week 2 post-dialysis | 5.287 μg/mL | Standard Deviation 5.2117 |
Secondary
Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite
Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.
Time frame: Pre-dialysis and post-dialysis on Week 2 and Week 16
Population: ITT Population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite | Week 2 pre-dialysis | 0.0136 μg/mL | Standard Deviation 0.00611 |
| Vadadustat 300 mg Once Daily (QD) | Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite | Week 16 pre-dialysis | 0.0129 μg/mL | Standard Deviation 0.01083 |
| Vadadustat 300 mg Once Daily (QD) | Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite | Week 2 post-dialysis | 0.0142 μg/mL | Standard Deviation 0.01016 |
| Vadadustat 300 mg Once Daily (QD) | Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite | Week 16 post-dialysis | 0.0100 μg/mL | Standard Deviation 0.00603 |
| Vadadustat 450 mg QD | Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite | Week 16 post-dialysis | 0.0087 μg/mL | Standard Deviation 0.00351 |
| Vadadustat 450 mg QD | Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite | Week 2 pre-dialysis | 0.0224 μg/mL | Standard Deviation 0.01889 |
| Vadadustat 450 mg QD | Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite | Week 2 post-dialysis | 0.0095 μg/mL | Standard Deviation 0.00246 |
| Vadadustat 450 mg QD | Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite | Week 16 pre-dialysis | 0.0210 μg/mL | Standard Deviation 0.007 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite | Week 2 pre-dialysis | 0.0800 μg/mL | — |
Secondary
Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite
Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.
Time frame: Pre-dialysis and post-dialysis on Week 2 and Week 16
Population: ITT Population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Week 16 pre-dialysis | 15.74 μg/mL | Standard Deviation 14.356 |
| Vadadustat 300 mg Once Daily (QD) | Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Week 2 post-dialysis | 8.725 μg/mL | Standard Deviation 7.6786 |
| Vadadustat 300 mg Once Daily (QD) | Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Week 2 pre-dialysis | 16.66 μg/mL | Standard Deviation 13.508 |
| Vadadustat 300 mg Once Daily (QD) | Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Week 16 post-dialysis | 7.833 μg/mL | Standard Deviation 5.5438 |
| Vadadustat 450 mg QD | Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Week 2 post-dialysis | 13.26 μg/mL | Standard Deviation 13.154 |
| Vadadustat 450 mg QD | Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Week 2 pre-dialysis | 26.36 μg/mL | Standard Deviation 21.111 |
| Vadadustat 450 mg QD | Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Week 16 post-dialysis | 8.408 μg/mL | Standard Deviation 6.4361 |
| Vadadustat 450 mg QD | Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Week 16 pre-dialysis | 17.19 μg/mL | Standard Deviation 13.266 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Week 2 pre-dialysis | 6.295 μg/mL | Standard Deviation 4.8326 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Week 16 post-dialysis | 2.998 μg/mL | Standard Deviation 2.5811 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Week 16 pre-dialysis | 7.843 μg/mL | Standard Deviation 8.0807 |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite | Week 2 post-dialysis | 3.101 μg/mL | Standard Deviation 2.219 |
Secondary
Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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. A TEAE 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. A SAE included AEs that met one or more of the following criteria/outcomes: death, lifethreatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, and congenital anomaly/birth defect.
Time frame: Up to Week 20
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 26 Participants |
| Vadadustat 300 mg Once Daily (QD) | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
| Vadadustat 450 mg QD | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 6 Participants |
| Vadadustat 450 mg QD | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 26 Participants |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 26 Participants |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 5 Participants |
Secondary
Number of Participants Who Received Blood Transfusion Rescue Therapy
Blood transfusion rescue therapy was administered in participants with Hgb ≤12.5 g/dL, and was stopped when Hgb reached ≥13.0 g/dL.
Time frame: Up to Week 16
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Number of Participants Who Received Blood Transfusion Rescue Therapy | 1 Participants |
| Vadadustat 450 mg QD | Number of Participants Who Received Blood Transfusion Rescue Therapy | 1 Participants |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Number of Participants Who Received Blood Transfusion Rescue Therapy | 0 Participants |
Secondary
Number of Participants Who Received Erythropoiesis-stimulating Agent (ESA) Rescue Therapy
ESA rescue therapy was administered in participants with Hgb ≤12.5 g/dL, and was stopped when Hgb reached ≥13.0 g/dL.
Time frame: Up to Week 16
Population: Intent-to-treat (ITT) Population: All participants who were assigned to study medication and received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Number of Participants Who Received Erythropoiesis-stimulating Agent (ESA) Rescue Therapy | 4 Participants |
| Vadadustat 450 mg QD | Number of Participants Who Received Erythropoiesis-stimulating Agent (ESA) Rescue Therapy | 6 Participants |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Number of Participants Who Received Erythropoiesis-stimulating Agent (ESA) Rescue Therapy | 2 Participants |
Secondary
Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings
A standard 12-lead ECG was performed following dosing in a supine position for approximately 5 minutes. ECGs were taken prior to vital sign assessments, circulatory access cannulation, and blood draws when possible. Clinical significance was determined by the investigator.
Time frame: Up to Week 20
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Vadadustat 450 mg QD | Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Parameters assessed for laboratory values included hematology, serum chemistry, urinalysis, iron indices, C-reactive protein, lipid profile, biomarkers, and pregnancy tests. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time frame: Up to Week 20
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| Vadadustat 450 mg QD | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Parameters assessed for vital signs included sitting blood pressure, pulse, respiratory rate, and body temperature. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time frame: Up to Week 20
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat 300 mg Once Daily (QD) | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 Participants |
| Vadadustat 450 mg QD | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 Participants |
| Vadadustat 450 mg 3 Times Per Week (TIW) | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 Participants |
Other Pre-specified
Mean Intravenous Iron Replacement Therapy
Intravenous iron was administered throughout the study to maintain ferritin levels in the range of ≥100 ng/mL to ≤1200 ng/mL.
Time frame: Baseline, Week 8, and Week 16