Anemia, Kidney Disease
Conditions
Keywords
anemia, chronic kidney disease, CKD, chronic renal insufficiency, renal impairment, erythropoietin, safety, efficacy, tolerability, pharmacokinetics
Brief summary
The purpose of this study is to evaluate the safety, pharmacodynamics and pharmacokinetics of repeat doses of orally administered AKB-6548 in pre-dialysis participants with anemia.
Interventions
DRUGAKB-6548
Different dose levels
Sponsors
Akebia Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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 of age, inclusive * Chronic Kidney Disease Stage 3 or Stage 4 * Hemoglobin (Hgb) \< 10.5 g/dl * TSAT \> 20% and CBC indicating normocytic red blood cell morphology Key
Exclusion criteria
* BMI \> 40 * Red blood cell transfusion within 12 weeks. * Androgen therapy within the previous 21 days prior to study dosing * Therapy with any approved or experimental erythropoiesis stimulating agent (ESA) within the 10 weeks prior to the Screening visit * Participants meeting the criteria of ESA resistance within the previous 4 months * Individual doses of intravenous iron of 250 mg or larger within the past 21 days * AST or ALT \>1.8x ULN. * Alkaline phosphatase \>2x ULN. * Total bilirubin \>1.5x ULN. * Uncontrolled hypertension * New York Heart Association Class III or IV congestive heart failure * Myocardial infarction, acute coronary syndrome, or stroke within 6 months prior to dosing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Hemoglobin (Hgb) on Day 29 | Baseline; Day 29 | Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates that hemoglobin concentration increased. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Total Red Blood Cell (RBC) Count on Day 29 | Baseline; Day 29 | Blood samples were collected to assess RBC count. Baseline RBC count was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates RBC count increased. |
| Mean Change From Baseline in Absolute Reticulocyte Count on Day 29 | Baseline; Day 29 | Blood samples were collected to assess reticulocyte count. Baseline absolute reticulocyte count was defined as the average of the 3 reticulocyte counts obtained prior to dosing (Screening, Pre- Baseline, and Baseline). A positive change from baseline indicates absolute reticulocyte count increased. |
| Mean Change From Baseline in Reticulocyte Hemoglobin (Hgb) Content on Day 29 | Baseline; Day 29 | Blood samples were collected to assess reticulocyte Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates reticulocyte Hgb content increased. |
| Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29 | Day 29 | Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). |
| Number of Participants With the Percentage Change From Baseline in Hemoglobin (Hgb) at Day 29 | Day 29 | Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). |
| Number of Participants With Percentage Change From Baseline in Hematocrit at Day 29 | Day 29 | Blood samples were collected to assess hematocrit. |
| Number of Participants With Percentage Change From Baseline in Red Blood Cell (RBC) Count at Day 29 | Day 29 | Blood samples were collected to assess RBC count. Baseline RBC count was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). |
| Number of Participants With Change From Baseline in Absolute Reticulocyte Count at Day 29 | Day 29 | Blood samples were collected to assess reticulocyte count. Baseline absolute reticulocyte count was defined as the average of the 3 reticulocyte counts obtained prior to dosing (Screening, Pre- Baseline, and Baseline). |
| Change From Baseline in Ferritin on Day 29 | Baseline; Day 29 | Blood samples were collected to assess ferritin. A positive change from baseline indicates ferritin content increased. |
| Mean Change From Baseline in Hematocrit on Day 29 | Baseline; Day 29 | Blood samples were collected to assess hematocrit. A positive change from baseline indicates hematocrit concentration increased. |
| Change From Baseline in Total Iron Binding Capacity on Day 29 | Baseline; Day 29 | Blood samples were collected to assess total iron binding capacity. A positive change from baseline indicates total iron binding capacity increased. |
| Change From Baseline in Transferrin Saturation on Day 29 | Baseline; Day 29 | Blood samples were collected to assess transferrin saturation. The transferrin saturation is the ratio of the serum iron concentration and the total iron-binding capacity, expressed as a percentage. A positive change from baseline indicates transferrin saturation increased. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to 2 weeks post 28 days of treatment | An Adverse Event (AE) was defined as any untoward medical occurrence, signs, symptoms, disease, or laboratory or physiological observations occurring in a participant administered with drug, regardless of a causal relationship with that treatment or usage. This also included all suspected adverse medication reactions, reactions from medication overdose, abuse, withdrawal, sensitivity, toxicity, unrelated illnesses, including worsening a pre-existing condition, injury, or accidents. Serious Adverse Events (SAEs) was defined as any life-threatening condition; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or death. |
| Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | Up to 2 weeks post 28 days of treatment | Parameters assessed for laboratory values included hematology, chemistry, urinalysis, and coagulation. The investigator was responsible for reviewing laboratory results for clinically significant changes. |
| Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values | Up to 2 weeks post 28 days of treatment | Parameters assessed for vital signs included sitting (at rest for a minimum of 5 minutes) heart rate, respiratory rate, body temperature, and blood pressure. The investigator was responsible for reviewing laboratory results for clinically significant changes. |
| Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings | Up to 2 weeks post 28 days of treatment | A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The investigator was responsible for reviewing laboratory results for clinical significance. |
| Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Up to 2 weeks post 28 days of treatment | A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The parameters evaluated from the participant ECG trace included PR interval, QT interval, QRS interval, and QTc (corrected). |
| Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29 | Pre-dose at Day 8, 15, 22 and 29 | Serum samples were collected from the participants at the defined time points. Trough concentration was defined as the concentration of drug in the blood immediately before the next dose is administered. Trough concentration was calculated using the validated liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method |
| Change From Baseline in Iron on Day 29 | Baseline; Day 29 | Blood samples were collected to assess iron. A positive change from baseline indicates iron content increased. |
Countries
United States
Participant flow
Pre-assignment details
This study enrolled Chronic Kidney Disease (CKD) Stage 3 or CKD Stage 4 participants. Per protocol, this is a pilot study and all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state as the Sponsor terminated the study early after enrolling 10 participants.
Participants by arm
| Arm | Count |
|---|---|
| Vadadustat Participants received Vadadustat orally, once daily for 28 days. Participants with Stage 3 and Stage 4 CKD started dosing with 400 milligrams (mg) and 300 mg Vadadustat, respectively. Thereafter, at each of the weekly study visits, dose adjustments were made based on pre-defined dose adjustment algorithm in 100 mg increments allowing a dose range of 200 mg/day to 700 mg/day for Stage 3 CKD participants and 200 mg/day to 600 mg/day for Stage 4 CKD participants. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Vadadustat |
|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 11.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Kidney disease stage Stage 3 | 6 Participants |
| Kidney disease stage Stage 4 | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 5 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Mean Change From Baseline in Hemoglobin (Hgb) on Day 29
Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates that hemoglobin concentration increased.
Time frame: Baseline; Day 29
Population: Full Analysis Set: All participants who received at least 1 dose of study medication. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Mean Change From Baseline in Hemoglobin (Hgb) on Day 29 | Baseline | 9.91 Grams per decilitre (g/dL) | Standard Deviation 0.63 |
| Vadadustat | Mean Change From Baseline in Hemoglobin (Hgb) on Day 29 | Change from Baseline on Day 29 | 0.63 Grams per decilitre (g/dL) | Standard Deviation 0.46 |
Comparison: Analysis of change from baseline on Day 29p-value: 0.002Wilcoxon signed rank test
Secondary
Change From Baseline in Ferritin on Day 29
Blood samples were collected to assess ferritin. A positive change from baseline indicates ferritin content increased.
Time frame: Baseline; Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Change From Baseline in Ferritin on Day 29 | Baseline | 324.0 Nanograms per millilitre | Standard Deviation 199.2 |
| Vadadustat | Change From Baseline in Ferritin on Day 29 | Change from Baseline on Day 29 | -52.3 Nanograms per millilitre | Standard Deviation 36.6 |
Comparison: Analysis of change from baseline on Day 29p-value: =0.002Wilcoxon signed rank test
Secondary
Change From Baseline in Iron on Day 29
Blood samples were collected to assess iron. A positive change from baseline indicates iron content increased.
Time frame: Baseline; Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Change From Baseline in Iron on Day 29 | Baseline | 69.4 Micrograms per decilitre | Standard Deviation 18.4 |
| Vadadustat | Change From Baseline in Iron on Day 29 | Change from Baseline on Day 29 | -8.2 Micrograms per decilitre | Standard Deviation 20.3 |
Comparison: Analysis of change from baseline on Day 29p-value: =0.2383Wilcoxon signed rank test
Secondary
Change From Baseline in Total Iron Binding Capacity on Day 29
Blood samples were collected to assess total iron binding capacity. A positive change from baseline indicates total iron binding capacity increased.
Time frame: Baseline; Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Change From Baseline in Total Iron Binding Capacity on Day 29 | Baseline | 266.4 Micrograms per decilitre | Standard Deviation 56.4 |
| Vadadustat | Change From Baseline in Total Iron Binding Capacity on Day 29 | Change from Baseline on Day 29 | 43.4 Micrograms per decilitre | Standard Deviation 34.8 |
Comparison: Analysis of change from baseline on Day 29p-value: =0.0039Wilcoxon signed rank test
Secondary
Change From Baseline in Transferrin Saturation on Day 29
Blood samples were collected to assess transferrin saturation. The transferrin saturation is the ratio of the serum iron concentration and the total iron-binding capacity, expressed as a percentage. A positive change from baseline indicates transferrin saturation increased.
Time frame: Baseline; Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Change From Baseline in Transferrin Saturation on Day 29 | Baseline | 26.1 Percentage | Standard Deviation 6.3 |
| Vadadustat | Change From Baseline in Transferrin Saturation on Day 29 | Change from Baseline on Day 29 | -6.4 Percentage | Standard Deviation 5.4 |
Comparison: Analysis of change from baseline on Day 29p-value: =0.0039Wilcoxon signed rank test
Secondary
Mean Change From Baseline in Absolute Reticulocyte Count on Day 29
Blood samples were collected to assess reticulocyte count. Baseline absolute reticulocyte count was defined as the average of the 3 reticulocyte counts obtained prior to dosing (Screening, Pre- Baseline, and Baseline). A positive change from baseline indicates absolute reticulocyte count increased.
Time frame: Baseline; Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Mean Change From Baseline in Absolute Reticulocyte Count on Day 29 | Baseline | 51076.00 Cells per Microlitre | Standard Deviation 24975.76 |
| Vadadustat | Mean Change From Baseline in Absolute Reticulocyte Count on Day 29 | Change from Baseline on Day 29 | 18647.00 Cells per Microlitre | Standard Deviation 18289.84 |
Comparison: Analysis of change from baseline on Day 29p-value: =0.0195Wilcoxon signed rank test
Secondary
Mean Change From Baseline in Hematocrit on Day 29
Blood samples were collected to assess hematocrit. A positive change from baseline indicates hematocrit concentration increased.
Time frame: Baseline; Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Mean Change From Baseline in Hematocrit on Day 29 | Baseline | 30.43 Percentage of red blood cells in blood | Standard Deviation 2.69 |
| Vadadustat | Mean Change From Baseline in Hematocrit on Day 29 | Change from Baseline on Day 29 | 1.62 Percentage of red blood cells in blood | Standard Deviation 1.71 |
Comparison: Analysis of change from baseline on Day 29p-value: =0.0156Wilcoxon signed rank test
Secondary
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The parameters evaluated from the participant ECG trace included PR interval, QT interval, QRS interval, and QTc (corrected).
Time frame: Up to 2 weeks post 28 days of treatment
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline PR Interval | 183.2 Milliseconds | Standard Deviation 42.6 |
| Vadadustat | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline PR Interval | -4.4 Milliseconds | Standard Deviation 18.1 |
| Vadadustat | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QT Interval | 415.6 Milliseconds | Standard Deviation 45.7 |
| Vadadustat | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QT Interval | 1.4 Milliseconds | Standard Deviation 20.3 |
| Vadadustat | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QRS Interval | 95.4 Milliseconds | Standard Deviation 21.4 |
| Vadadustat | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QRS Interval | 3.4 Milliseconds | Standard Deviation 6.7 |
| Vadadustat | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QTC Interval | 429.9 Milliseconds | Standard Deviation 30.5 |
| Vadadustat | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QTC Interval | 4.1 Milliseconds | Standard Deviation 8.3 |
Secondary
Mean Change From Baseline in Reticulocyte Hemoglobin (Hgb) Content on Day 29
Blood samples were collected to assess reticulocyte Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates reticulocyte Hgb content increased.
Time frame: Baseline; Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Mean Change From Baseline in Reticulocyte Hemoglobin (Hgb) Content on Day 29 | Baseline | 31.49 Picograms | Standard Deviation 2.44 |
| Vadadustat | Mean Change From Baseline in Reticulocyte Hemoglobin (Hgb) Content on Day 29 | Change from Baseline on Day 29 | 0.13 Picograms | Standard Deviation 0.84 |
Comparison: Analysis of change from baseline on Day 29p-value: =0.8262Wilcoxon signed rank test
Secondary
Mean Change From Baseline in Total Red Blood Cell (RBC) Count on Day 29
Blood samples were collected to assess RBC count. Baseline RBC count was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline). A positive change from baseline indicates RBC count increased.
Time frame: Baseline; Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Mean Change From Baseline in Total Red Blood Cell (RBC) Count on Day 29 | Baseline | 3.313 Million cells per cubic millimeter | Standard Deviation 0.389 |
| Vadadustat | Mean Change From Baseline in Total Red Blood Cell (RBC) Count on Day 29 | Change from Baseline on Day 29 | 0.167 Million cells per cubic millimeter | Standard Deviation 0.17 |
Comparison: Analysis of change from baseline on Day 29p-value: 0.0098Wilcoxon signed rank test
Secondary
Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29
Serum samples were collected from the participants at the defined time points. Trough concentration was defined as the concentration of drug in the blood immediately before the next dose is administered. Trough concentration was calculated using the validated liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
Time frame: Pre-dose at Day 8, 15, 22 and 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29 | Day 8 | 3260.6 nanograms per millilitre | Standard Deviation 2763.8 |
| Vadadustat | Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29 | Day 15 | 3826.3 nanograms per millilitre | Standard Deviation 2537.5 |
| Vadadustat | Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29 | Day 22 | 3667.4 nanograms per millilitre | Standard Deviation 1933.4 |
| Vadadustat | Mean Trough Concentrations of Vadadustat at Day 8, 15, 22 and 29 | Day 29 | 5622.4 nanograms per millilitre | Standard Deviation 5385.4 |
Secondary
Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29
Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline).
Time frame: Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat | Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29 | Change from baseline ≥ 0.4 grams per decilitre | 6 Participants |
| Vadadustat | Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29 | Change from baseline ≥ 0.6 grams per decilitre | 5 Participants |
| Vadadustat | Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29 | Change from baseline ≥ 0.8 grams per decilitre | 3 Participants |
| Vadadustat | Number of Participants With Absolute Change From Baseline in Hemoglobin (Hgb) at Day 29 | Change from baseline ≥ 1.0 grams per decilitre | 2 Participants |
Secondary
Number of Participants With Change From Baseline in Absolute Reticulocyte Count at Day 29
Blood samples were collected to assess reticulocyte count. Baseline absolute reticulocyte count was defined as the average of the 3 reticulocyte counts obtained prior to dosing (Screening, Pre- Baseline, and Baseline).
Time frame: Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat | Number of Participants With Change From Baseline in Absolute Reticulocyte Count at Day 29 | Change from Baseline ≥ 6000 cells per microlitre | 8 Participants |
| Vadadustat | Number of Participants With Change From Baseline in Absolute Reticulocyte Count at Day 29 | Change from Baseline ≥ 12000 cells per microlitre | 7 Participants |
| Vadadustat | Number of Participants With Change From Baseline in Absolute Reticulocyte Count at Day 29 | Change from Baseline ≥ 18000 cells per microlitre | 6 Participants |
Secondary
Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings
A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The investigator was responsible for reviewing laboratory results for clinical significance.
Time frame: Up to 2 weeks post 28 days of treatment
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat | Number of Participants With Clinically 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, chemistry, urinalysis, and coagulation. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time frame: Up to 2 weeks post 28 days of treatment
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat | 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 Sign Values
Parameters assessed for vital signs included sitting (at rest for a minimum of 5 minutes) heart rate, respiratory rate, body temperature, and blood pressure. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time frame: Up to 2 weeks post 28 days of treatment
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat | Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values | 0 Participants |
Secondary
Number of Participants With Percentage Change From Baseline in Hematocrit at Day 29
Blood samples were collected to assess hematocrit.
Time frame: Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat | Number of Participants With Percentage Change From Baseline in Hematocrit at Day 29 | Percent change from Baseline ≥ 5.0% | 6 Participants |
| Vadadustat | Number of Participants With Percentage Change From Baseline in Hematocrit at Day 29 | Percent change from Baseline ≥ 7.5% | 2 Participants |
| Vadadustat | Number of Participants With Percentage Change From Baseline in Hematocrit at Day 29 | Percent change from Baseline ≥ 10.0% | 2 Participants |
Secondary
Number of Participants With Percentage Change From Baseline in Red Blood Cell (RBC) Count at Day 29
Blood samples were collected to assess RBC count. Baseline RBC count was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline).
Time frame: Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat | Number of Participants With Percentage Change From Baseline in Red Blood Cell (RBC) Count at Day 29 | Percent change from Baseline ≥ 5.0% | 5 Participants |
| Vadadustat | Number of Participants With Percentage Change From Baseline in Red Blood Cell (RBC) Count at Day 29 | Percent change from Baseline ≥ 7.5% | 3 Participants |
| Vadadustat | Number of Participants With Percentage Change From Baseline in Red Blood Cell (RBC) Count at Day 29 | Percent change from Baseline ≥ 10.0% | 3 Participants |
Secondary
Number of Participants With the Percentage Change From Baseline in Hemoglobin (Hgb) at Day 29
Blood samples were collected to assess Hgb. Baseline Hgb was defined as the average of the 2 samples obtained prior to dosing (Pre-Baseline and Baseline).
Time frame: Day 29
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat | Number of Participants With the Percentage Change From Baseline in Hemoglobin (Hgb) at Day 29 | Percent change from Baseline ≥ 5.0% | 5 Participants |
| Vadadustat | Number of Participants With the Percentage Change From Baseline in Hemoglobin (Hgb) at Day 29 | Percent change from Baseline ≥ 7.5% | 3 Participants |
| Vadadustat | Number of Participants With the Percentage Change From Baseline in Hemoglobin (Hgb) at Day 29 | Percent change from Baseline ≥ 10.0% | 3 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An Adverse Event (AE) was defined as any untoward medical occurrence, signs, symptoms, disease, or laboratory or physiological observations occurring in a participant administered with drug, regardless of a causal relationship with that treatment or usage. This also included all suspected adverse medication reactions, reactions from medication overdose, abuse, withdrawal, sensitivity, toxicity, unrelated illnesses, including worsening a pre-existing condition, injury, or accidents. Serious Adverse Events (SAEs) was defined as any life-threatening condition; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or death.
Time frame: Up to 2 weeks post 28 days of treatment
Population: Full analysis set population. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs | 5 Participants |
| Vadadustat | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | SAEs | 0 Participants |
| Vadadustat | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Deaths | 0 Participants |