Anemia, Chronic Kidney Disease
Conditions
Keywords
anemia, chronic kidney disease, CKD, chronic renal insufficiency, renal impairment, erythropoietin, kidney, oral anemia treatment, hemoglobin, hypoxia-inducible factor, HIF, hypoxia-inducible factor prolyl-hydroxylase inhibitor, HIF-PHI, efficacy, safety, 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 Chronic Kidney Disease (pre-dialysis) with anemia with dosing for 20 weeks.
Interventions
DRUGAKB-6548
Oral dose administered once daily for 20 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.
DRUGPlacebo
Oral Placebo administered once daily for 20 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.
Sponsors
Akebia Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 82 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 18 to 82 years of age, inclusive * Chronic Kidney Disease with a GFR category of G3a-G5 and not yet on dialysis * eGFR ≥ 10 and ≤ 65 mL/minute/1.73 m2 * Anemia secondary to CKD with an ESA status and a Screening HGB as per protocol * Iron replete with ferritin and TSAT levels as defined per protocol Key
Exclusion criteria
* BMI \> 44.0 kg/m2 * Red blood cell transfusion within 11 weeks prior to the Screening visit * Androgen therapy within the previous 21 days prior to the Screening visit * Intravenous iron within the past 4 weeks prior to the Screening visit * AST or ALT \>1.8x ULN, alkaline phosphatase \>2x ULN, or total bilirubin \>1.5x ULN * Screening ECG with QTc \> 500 msec * Uncontrolled hypertension * Class III or IV congestive heart failure * Myocardial infarction, acute coronary syndrome, or stroke within 6 months prior to the Screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a Successful Hemoglobin Response | Weeks 19 and 20 | Hemoglobin (Hgb) response was defined as participants with mean Hgb ≥11.0 grams per deciliter (g/dL) (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving Erythropoiesis-Stimulating Agents (ESA) or transfusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) | Up to 20 Weeks | 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. |
| Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Treatment naïve Group | Weeks 19 and 20 | Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Treatment Naïve group, defined as participants who had never received treatment with an ESA and who had a screening Hgb level of ≤10.5 g/dL. |
| Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Previously Treated Group | Weeks 19 and 20 | Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Previously Treated group, defined as participants who had previously received ≥1 dose of an ESA, had been off of ESA therapy for ≥11 weeks at the time of screening, and had a screening Hgb level of ≤10.5 g/dL. |
| Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Actively Treated Group | Weeks 19 and 20 | Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Actively Treated group, defined as participants who had been actively treated with an ESA for a minimum of 4 months before screening, had received at least 2 doses within the last 4 months, had received their last dose within 6 weeks before screening, and had a screening Hgb level ≥9.5 g/dL and ≤12.0 g/dL. |
| Percentage of Participants Achieving a Successful Hemoglobin Response, Analyzed in mITT Population | Weeks 19 and 20 | Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Analysis of this secondary outcome measure was performed in the mITT population. |
| Change From Baseline in Hemoglobin | Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 | Blood samples were collected to assess Hgb. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated Hgb concentration increased. |
| Absolute Values of Hemoglobin | Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 | Blood samples were collected at indicated time points for analysis of hemoglobin |
| Change From Baseline in Hematocrit | Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 | Blood samples were collected to assess Hematocrit. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated Hematocrit concentration increased. |
| Absolute Values of Hematocrit | Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 | Blood samples were collected at indicated time points for analysis of Hematocrit. |
| Change From Baseline in Red Blood Cell Count | Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 | Blood samples were collected to assess red blood cell count. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated red blood cell count increased. |
| Absolute Values of Red Blood Cell Count | Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 | Blood samples were collected at indicated time points for analysis of red blood cell count. |
| Change From Baseline in Reticulocyte Count | Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 | Blood samples were collected to assess reticulocyte count. Baseline was defined as mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated reticulocyte count increased. |
| Absolute Values of Reticulocyte Count | Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20 | Blood samples were collected at indicated time points for analysis of reticulocyte count. |
| Percentage of Participants Who Received ESA Rescue | Up to 20 Weeks | Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia. |
| Mean Number of ESA Rescue Doses Administered Per Participant | Up to 20 Weeks | Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia. |
| Percentage of Participants Who Received Packed Red Blood Cell Transfusion Rescue | Up to 20 Weeks | Participants were administered packed red blood cell transfusion as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia |
| Number of Packed Red Blood Cell Transfusion Administered Per Participant | Up to 20 Weeks | Participants were administered packed red blood cells as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia. |
| Time to First Transfusion or ESA Rescue Medication Intake | Up to 20 Weeks | Rescue therapy was defined as red blood cell transfusion or ESA administration in participants meeting Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia. |
| Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | Up to 20 Weeks | Parameters assessed for laboratory values included hematology, serum chemistry, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant changes. |
| Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | Up to 20 Weeks | 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 20 Weeks | 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. |
| Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings | Up to 20 Weeks | A Baseline physical examination was performed at screening. Otherwise, abbreviated physical examinations were conducted and were to include heart, lung, and abdomen. The investigator was responsible for reviewing laboratory results for clinically significant changes. |
| Percentage of Participants With Hemoglobin Value ≥13.0 g/dL at Any Time During the Study | Up to 20 Weeks | Participants who have experienced an excursion in Hgb to ≥13.0 g/dL at any time during the study were considered as failures. Data was presented for failures. |
| Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value | Weeks 19 and 20 | Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing). Analysis of this secondary outcome measure is a reanalysis of the primary outcome measure whereby the response was determined solely by the Hgb value and receiving rescue therapy did not make the participant a failure. |
Other
| Measure | Time frame |
|---|---|
| Exploratory: Change From Baseline in Transferrin Saturation | Baseline and up to Week 20 |
| Exploratory: Mean Weekly Dose of Intravenous Elemental Iron Administered | Baseline and up to Week 20 |
| Exploratory: Absolute Values of Iron and Total Iron Binding Capacity (TIBC) | Baseline and up to Week 20 |
| Exploratory: Absolute Values of Transferrin | Baseline and up to Week 20 |
| Exploratory: Absolute Values of Transferrin Saturation | Baseline and up to Week 20 |
| Exploratory: Absolute Values of Reticulocyte Hemoglobin Content | Baseline and up to Week 20 |
| Exploratory: Change From Baseline in Reticulocyte Hemoglobin Content | Baseline and up to Week 20 |
| Exploratory: Change From Baseline in Hemoglobin A1c | Baseline and up to Week 20 |
| Exploratory: Absolute Values of Hemoglobin A1c | Baseline and up to Week 20 |
| Exploratory: Absolute Values of Lipids | Baseline and up to Week 20 |
| Exploratory: Change From Baseline in Lipids | Baseline and up to Week 20 |
| Exploratory: Change From Baseline in Hepcidin | Baseline and up to Week 20 |
| Exploratory: Absolute Values of Hepcidin | Baseline and up to Week 20 |
| Exploratory: Change From Baseline in Vascular Endothelial Growth Factor (VEGF) | Baseline and up to Week 20 |
| Exploratory: Absolute Values of Interleukin 6, Cystatin C, Intact Parathyroid Hormone, and Calcitonin | Baseline and up to Week 20 |
| Exploratory: Change From Baseline in Interleukin 6, Cystatin C, Intact Parathyroid Hormone, and Calcitonin | Baseline and up to Week 20 |
| Exploratory: Neurocognitive Functioning as a Measure | Baseline and up to Week 20 |
| Exploratory: Patient-Reported Outcome Measures | Baseline and up to Week 20 |
| Exploratory: Plasma Concentrations of Vadadustat and Its Glucuronide Metabolites | Baseline and up to Week 20 |
| Exploratory: Change From Baseline in Transferrin | Baseline and up to Week 20 |
| Exploratory: Change From Baseline in Iron and Total Iron Binding Capacity (TIBC) | Baseline and up to Week 20 |
Countries
United States
Participant flow
Pre-assignment details
A total of 210 participants entered the study and 209 were randomized in a 2:1 ratio to receive Vadadustat or Placebo. However, 1 participant received Placebo in error.
Participants by arm
| Arm | Count |
|---|---|
| Vadadustat Participants received Vadadustat 450 milligrams (mg), as 3 tablets once daily (QD) for 20 consecutive weeks. The dose of study medication was increased to a maximum of 600 mg/day or decreased to 150 mg/day based on Hgb response. Participants received an iron supplement to maintain ferritin levels. | 138 |
| Placebo Participants received matching Placebo, as 3 tablets once daily (QD) for 20 consecutive weeks. Placebo was provided as white to off-white, oval film-coated tablets for oral administration. Participants received an iron supplement to maintain ferritin levels. | 72 |
| Total | 210 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 3 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Non- Compliance | 1 | 0 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Sponsor Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 0 |
| Overall Study | Worsening of Anemia | 1 | 0 |
| Overall Study | Worsening of CKD | 6 | 4 |
Baseline characteristics
| Characteristic | Placebo | Total | Vadadustat |
|---|---|---|---|
| Age, Continuous | 65.9 years STANDARD_DEVIATION 12.33 | 66.4 years STANDARD_DEVIATION 10.81 | 66.6 years STANDARD_DEVIATION 9.97 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 68 Participants | 49 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 49 Participants | 132 Participants | 83 Participants |
| Sex: Female, Male Female | 34 Participants | 115 Participants | 81 Participants |
| Sex: Female, Male Male | 38 Participants | 95 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 138 | 0 / 72 |
| other Total, other adverse events | 58 / 138 | 29 / 72 |
| serious Total, serious adverse events | 33 / 138 | 11 / 72 |
Outcome results
Primary
Percentage of Participants Achieving a Successful Hemoglobin Response
Hemoglobin (Hgb) response was defined as participants with mean Hgb ≥11.0 grams per deciliter (g/dL) (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving Erythropoiesis-Stimulating Agents (ESA) or transfusion.
Time frame: Weeks 19 and 20
Population: Per Protocol (PP) Population: participants in modified intent-to-treat (MITT) Population who had completed the study and had efficacy data through Week 20, had a study medication compliance of ≥ 80%, and did not have any protocol deviations. Only participants with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vadadustat | Percentage of Participants Achieving a Successful Hemoglobin Response | 54.9 Percentage of participants |
| Placebo | Percentage of Participants Achieving a Successful Hemoglobin Response | 10.3 Percentage of participants |
p-value: =0.000195% CI: [3.3505, 39.2931]Fisher Exact
Secondary
Absolute Values of Hematocrit
Blood samples were collected at indicated time points for analysis of Hematocrit.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Absolute Values of Hematocrit | Week 2 | 31.2 Percentage of red blood cells in blood | Standard Deviation 3.06 |
| Vadadustat | Absolute Values of Hematocrit | Week 12 | 33.5 Percentage of red blood cells in blood | Standard Deviation 3.19 |
| Vadadustat | Absolute Values of Hematocrit | Week 6 | 33.1 Percentage of red blood cells in blood | Standard Deviation 3.21 |
| Vadadustat | Absolute Values of Hematocrit | Week 16 | 34 Percentage of red blood cells in blood | Standard Deviation 3.02 |
| Vadadustat | Absolute Values of Hematocrit | Week 4 | 32.4 Percentage of red blood cells in blood | Standard Deviation 3.17 |
| Vadadustat | Absolute Values of Hematocrit | Week 19 | 33.7 Percentage of red blood cells in blood | Standard Deviation 2.83 |
| Vadadustat | Absolute Values of Hematocrit | Week 8 | 33.2 Percentage of red blood cells in blood | Standard Deviation 3.05 |
| Vadadustat | Absolute Values of Hematocrit | Week 20 | 33.6 Percentage of red blood cells in blood | Standard Deviation 3.19 |
| Vadadustat | Absolute Values of Hematocrit | Baseline | 30.4 Percentage of red blood cells in blood | Standard Deviation 2.96 |
| Placebo | Absolute Values of Hematocrit | Week 20 | 30.4 Percentage of red blood cells in blood | Standard Deviation 2.7 |
| Placebo | Absolute Values of Hematocrit | Baseline | 30.3 Percentage of red blood cells in blood | Standard Deviation 2.9 |
| Placebo | Absolute Values of Hematocrit | Week 2 | 29.7 Percentage of red blood cells in blood | Standard Deviation 2.62 |
| Placebo | Absolute Values of Hematocrit | Week 4 | 29.7 Percentage of red blood cells in blood | Standard Deviation 2.72 |
| Placebo | Absolute Values of Hematocrit | Week 6 | 29.4 Percentage of red blood cells in blood | Standard Deviation 2.46 |
| Placebo | Absolute Values of Hematocrit | Week 8 | 29.3 Percentage of red blood cells in blood | Standard Deviation 3.05 |
| Placebo | Absolute Values of Hematocrit | Week 12 | 30.2 Percentage of red blood cells in blood | Standard Deviation 2.05 |
| Placebo | Absolute Values of Hematocrit | Week 16 | 30.3 Percentage of red blood cells in blood | Standard Deviation 2.87 |
| Placebo | Absolute Values of Hematocrit | Week 19 | 30.7 Percentage of red blood cells in blood | Standard Deviation 2.83 |
Secondary
Absolute Values of Hemoglobin
Blood samples were collected at indicated time points for analysis of hemoglobin
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Absolute Values of Hemoglobin | Week 6 | 10.61 g/dL | Standard Deviation 0.996 |
| Vadadustat | Absolute Values of Hemoglobin | Week 2 | 10.02 g/dL | Standard Deviation 0.909 |
| Vadadustat | Absolute Values of Hemoglobin | Week 8 | 10.66 g/dL | Standard Deviation 0.987 |
| Vadadustat | Absolute Values of Hemoglobin | Week 19 | 10.74 g/dL | Standard Deviation 0.881 |
| Vadadustat | Absolute Values of Hemoglobin | Week 12 | 10.87 g/dL | Standard Deviation 0.958 |
| Vadadustat | Absolute Values of Hemoglobin | Week 4 | 10.35 g/dL | Standard Deviation 0.979 |
| Vadadustat | Absolute Values of Hemoglobin | Week 16 | 10.79 g/dL | Standard Deviation 0.895 |
| Vadadustat | Absolute Values of Hemoglobin | Week 20 | 10.88 g/dL | Standard Deviation 1.002 |
| Vadadustat | Absolute Values of Hemoglobin | Baseline | 9.94 g/dL | Standard Deviation 0.861 |
| Placebo | Absolute Values of Hemoglobin | Week 20 | 9.93 g/dL | Standard Deviation 0.859 |
| Placebo | Absolute Values of Hemoglobin | Week 16 | 9.83 g/dL | Standard Deviation 0.841 |
| Placebo | Absolute Values of Hemoglobin | Week 19 | 9.93 g/dL | Standard Deviation 0.897 |
| Placebo | Absolute Values of Hemoglobin | Week 2 | 9.74 g/dL | Standard Deviation 0.714 |
| Placebo | Absolute Values of Hemoglobin | Week 4 | 9.7 g/dL | Standard Deviation 0.733 |
| Placebo | Absolute Values of Hemoglobin | Week 6 | 9.6 g/dL | Standard Deviation 0.758 |
| Placebo | Absolute Values of Hemoglobin | Week 8 | 9.6 g/dL | Standard Deviation 0.848 |
| Placebo | Absolute Values of Hemoglobin | Week 12 | 9.82 g/dL | Standard Deviation 0.682 |
| Placebo | Absolute Values of Hemoglobin | Baseline | 9.96 g/dL | Standard Deviation 0.79 |
Secondary
Absolute Values of Red Blood Cell Count
Blood samples were collected at indicated time points for analysis of red blood cell count.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Absolute Values of Red Blood Cell Count | Week 2 | 3.39 10^6 cells per microliter | Standard Deviation 0.418 |
| Vadadustat | Absolute Values of Red Blood Cell Count | Week 12 | 3.68 10^6 cells per microliter | Standard Deviation 0.457 |
| Vadadustat | Absolute Values of Red Blood Cell Count | Week 6 | 3.57 10^6 cells per microliter | Standard Deviation 0.412 |
| Vadadustat | Absolute Values of Red Blood Cell Count | Week 16 | 3.69 10^6 cells per microliter | Standard Deviation 0.44 |
| Vadadustat | Absolute Values of Red Blood Cell Count | Week 4 | 3.51 10^6 cells per microliter | Standard Deviation 0.409 |
| Vadadustat | Absolute Values of Red Blood Cell Count | Week 19 | 3.67 10^6 cells per microliter | Standard Deviation 0.415 |
| Vadadustat | Absolute Values of Red Blood Cell Count | Week 8 | 3.61 10^6 cells per microliter | Standard Deviation 0.421 |
| Vadadustat | Absolute Values of Red Blood Cell Count | Week 20 | 3.7 10^6 cells per microliter | Standard Deviation 0.453 |
| Vadadustat | Absolute Values of Red Blood Cell Count | Baseline | 3.38 10^6 cells per microliter | Standard Deviation 0.402 |
| Placebo | Absolute Values of Red Blood Cell Count | Week 20 | 3.33 10^6 cells per microliter | Standard Deviation 0.318 |
| Placebo | Absolute Values of Red Blood Cell Count | Baseline | 3.34 10^6 cells per microliter | Standard Deviation 0.322 |
| Placebo | Absolute Values of Red Blood Cell Count | Week 2 | 3.25 10^6 cells per microliter | Standard Deviation 0.321 |
| Placebo | Absolute Values of Red Blood Cell Count | Week 4 | 3.24 10^6 cells per microliter | Standard Deviation 0.317 |
| Placebo | Absolute Values of Red Blood Cell Count | Week 6 | 3.2 10^6 cells per microliter | Standard Deviation 0.321 |
| Placebo | Absolute Values of Red Blood Cell Count | Week 8 | 3.21 10^6 cells per microliter | Standard Deviation 0.377 |
| Placebo | Absolute Values of Red Blood Cell Count | Week 12 | 3.27 10^6 cells per microliter | Standard Deviation 0.295 |
| Placebo | Absolute Values of Red Blood Cell Count | Week 16 | 3.29 10^6 cells per microliter | Standard Deviation 0.343 |
| Placebo | Absolute Values of Red Blood Cell Count | Week 19 | 3.32 10^6 cells per microliter | Standard Deviation 0.332 |
Secondary
Absolute Values of Reticulocyte Count
Blood samples were collected at indicated time points for analysis of reticulocyte count.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Absolute Values of Reticulocyte Count | Week 2 | 2.74 10^6 cells per microliter | Standard Deviation 1.069 |
| Vadadustat | Absolute Values of Reticulocyte Count | Week 12 | 2.02 10^6 cells per microliter | Standard Deviation 0.959 |
| Vadadustat | Absolute Values of Reticulocyte Count | Week 6 | 2.32 10^6 cells per microliter | Standard Deviation 0.996 |
| Vadadustat | Absolute Values of Reticulocyte Count | Week 16 | 2.13 10^6 cells per microliter | Standard Deviation 0.992 |
| Vadadustat | Absolute Values of Reticulocyte Count | Week 4 | 2.44 10^6 cells per microliter | Standard Deviation 0.962 |
| Vadadustat | Absolute Values of Reticulocyte Count | Week 19 | 2.21 10^6 cells per microliter | Standard Deviation 1.297 |
| Vadadustat | Absolute Values of Reticulocyte Count | Week 8 | 2.05 10^6 cells per microliter | Standard Deviation 0.884 |
| Vadadustat | Absolute Values of Reticulocyte Count | Week 20 | 2.17 10^6 cells per microliter | Standard Deviation 0.954 |
| Vadadustat | Absolute Values of Reticulocyte Count | Baseline | 2.12 10^6 cells per microliter | Standard Deviation 0.858 |
| Placebo | Absolute Values of Reticulocyte Count | Week 20 | 2.1 10^6 cells per microliter | Standard Deviation 0.88 |
| Placebo | Absolute Values of Reticulocyte Count | Baseline | 1.97 10^6 cells per microliter | Standard Deviation 0.816 |
| Placebo | Absolute Values of Reticulocyte Count | Week 2 | 1.91 10^6 cells per microliter | Standard Deviation 0.727 |
| Placebo | Absolute Values of Reticulocyte Count | Week 4 | 2.06 10^6 cells per microliter | Standard Deviation 0.731 |
| Placebo | Absolute Values of Reticulocyte Count | Week 6 | 2.07 10^6 cells per microliter | Standard Deviation 0.897 |
| Placebo | Absolute Values of Reticulocyte Count | Week 8 | 2.09 10^6 cells per microliter | Standard Deviation 0.85 |
| Placebo | Absolute Values of Reticulocyte Count | Week 12 | 2 10^6 cells per microliter | Standard Deviation 0.846 |
| Placebo | Absolute Values of Reticulocyte Count | Week 16 | 1.96 10^6 cells per microliter | Standard Deviation 0.83 |
| Placebo | Absolute Values of Reticulocyte Count | Week 19 | 1.92 10^6 cells per microliter | Standard Deviation 0.77 |
Secondary
Change From Baseline in Hematocrit
Blood samples were collected to assess Hematocrit. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated Hematocrit concentration increased.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Change From Baseline in Hematocrit | Week 2 | 0.8 Percentage of red blood cells in blood | Standard Deviation 2.46 |
| Vadadustat | Change From Baseline in Hematocrit | Week 12 | 3 Percentage of red blood cells in blood | Standard Deviation 3.5 |
| Vadadustat | Change From Baseline in Hematocrit | Week 6 | 2.5 Percentage of red blood cells in blood | Standard Deviation 3.55 |
| Vadadustat | Change From Baseline in Hematocrit | Week 16 | 3.3 Percentage of red blood cells in blood | Standard Deviation 3.48 |
| Vadadustat | Change From Baseline in Hematocrit | Week 4 | 2 Percentage of red blood cells in blood | Standard Deviation 2.87 |
| Vadadustat | Change From Baseline in Hematocrit | Week 19 | 3.1 Percentage of red blood cells in blood | Standard Deviation 3.51 |
| Vadadustat | Change From Baseline in Hematocrit | Week 8 | 2.7 Percentage of red blood cells in blood | Standard Deviation 3.44 |
| Vadadustat | Change From Baseline in Hematocrit | Week 20 | 3 Percentage of red blood cells in blood | Standard Deviation 3.8 |
| Vadadustat | Change From Baseline in Hematocrit | Baseline | 30.4 Percentage of red blood cells in blood | Standard Deviation 2.96 |
| Placebo | Change From Baseline in Hematocrit | Week 20 | 0.1 Percentage of red blood cells in blood | Standard Deviation 3.13 |
| Placebo | Change From Baseline in Hematocrit | Baseline | 30.3 Percentage of red blood cells in blood | Standard Deviation 2.9 |
| Placebo | Change From Baseline in Hematocrit | Week 2 | -0.6 Percentage of red blood cells in blood | Standard Deviation 1.97 |
| Placebo | Change From Baseline in Hematocrit | Week 4 | -0.5 Percentage of red blood cells in blood | Standard Deviation 2.33 |
| Placebo | Change From Baseline in Hematocrit | Week 6 | -1 Percentage of red blood cells in blood | Standard Deviation 2.87 |
| Placebo | Change From Baseline in Hematocrit | Week 8 | -1 Percentage of red blood cells in blood | Standard Deviation 3.15 |
| Placebo | Change From Baseline in Hematocrit | Week 12 | -0.3 Percentage of red blood cells in blood | Standard Deviation 2.95 |
| Placebo | Change From Baseline in Hematocrit | Week 16 | -0.1 Percentage of red blood cells in blood | Standard Deviation 3.24 |
| Placebo | Change From Baseline in Hematocrit | Week 19 | 0 Percentage of red blood cells in blood | Standard Deviation 3.19 |
Comparison: Week 2p-value: <0.0001t-test, 2 sided
Comparison: Week 4p-value: <0.0001t-test, 2 sided
Comparison: Week 6p-value: <0.0001t-test, 2 sided
Comparison: Week 8p-value: <0.0001t-test, 2 sided
Comparison: Week 12p-value: <0.0001t-test, 2 sided
Comparison: Week 16p-value: <0.0001t-test, 2 sided
Comparison: Week 19p-value: <0.0001t-test, 2 sided
Comparison: Week 20p-value: <0.0001t-test, 2 sided
Secondary
Change From Baseline in Hemoglobin
Blood samples were collected to assess Hgb. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated Hgb concentration increased.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Change From Baseline in Hemoglobin | Week 2 | 0.1 g/dL | Standard Deviation 0.756 |
| Vadadustat | Change From Baseline in Hemoglobin | Week 12 | 0.9 g/dL | Standard Deviation 1.066 |
| Vadadustat | Change From Baseline in Hemoglobin | Week 6 | 0.63 g/dL | Standard Deviation 1.059 |
| Vadadustat | Change From Baseline in Hemoglobin | Week 16 | 0.76 g/dL | Standard Deviation 1.055 |
| Vadadustat | Change From Baseline in Hemoglobin | Week 4 | 0.39 g/dL | Standard Deviation 0.868 |
| Vadadustat | Change From Baseline in Hemoglobin | Week 19 | 0.73 g/dL | Standard Deviation 1.063 |
| Vadadustat | Change From Baseline in Hemoglobin | Week 8 | 0.69 g/dL | Standard Deviation 1.087 |
| Vadadustat | Change From Baseline in Hemoglobin | Week 20 | 0.88 g/dL | Standard Deviation 1.161 |
| Vadadustat | Change From Baseline in Hemoglobin | Baseline | 9.94 g/dL | Standard Deviation 0.861 |
| Placebo | Change From Baseline in Hemoglobin | Week 20 | -0.08 g/dL | Standard Deviation 0.933 |
| Placebo | Change From Baseline in Hemoglobin | Baseline | 9.96 g/dL | Standard Deviation 0.79 |
| Placebo | Change From Baseline in Hemoglobin | Week 2 | -0.22 g/dL | Standard Deviation 0.564 |
| Placebo | Change From Baseline in Hemoglobin | Week 4 | -0.25 g/dL | Standard Deviation 0.679 |
| Placebo | Change From Baseline in Hemoglobin | Week 6 | -0.41 g/dL | Standard Deviation 0.835 |
| Placebo | Change From Baseline in Hemoglobin | Week 8 | -0.4 g/dL | Standard Deviation 0.878 |
| Placebo | Change From Baseline in Hemoglobin | Week 12 | -0.2 g/dL | Standard Deviation 0.864 |
| Placebo | Change From Baseline in Hemoglobin | Week 16 | -0.18 g/dL | Standard Deviation 0.963 |
| Placebo | Change From Baseline in Hemoglobin | Week 19 | -0.16 g/dL | Standard Deviation 0.926 |
Comparison: Week 2p-value: =0.0019t-test, 2 sided
Comparison: Week 4p-value: <0.0001t-test, 2 sided
Comparison: Week 6p-value: <0.0001t-test, 2 sided
Comparison: Week 8p-value: <0.0001t-test, 2 sided
Comparison: Week 12p-value: <0.0001t-test, 2 sided
Comparison: Week 16p-value: <0.0001t-test, 2 sided
Comparison: Week 19p-value: <0.0001t-test, 2 sided
Comparison: Week 20p-value: <0.0001t-test, 2 sided
Secondary
Change From Baseline in Red Blood Cell Count
Blood samples were collected to assess red blood cell count. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated red blood cell count increased.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Change From Baseline in Red Blood Cell Count | Week 2 | 0.02 10^6 cells per microliter | Standard Deviation 0.243 |
| Vadadustat | Change From Baseline in Red Blood Cell Count | Week 12 | 0.3 10^6 cells per microliter | Standard Deviation 0.357 |
| Vadadustat | Change From Baseline in Red Blood Cell Count | Week 6 | 0.18 10^6 cells per microliter | Standard Deviation 0.346 |
| Vadadustat | Change From Baseline in Red Blood Cell Count | Week 16 | 0.28 10^6 cells per microliter | Standard Deviation 0.363 |
| Vadadustat | Change From Baseline in Red Blood Cell Count | Week 4 | 0.12 10^6 cells per microliter | Standard Deviation 0.277 |
| Vadadustat | Change From Baseline in Red Blood Cell Count | Week 19 | 0.26 10^6 cells per microliter | Standard Deviation 0.374 |
| Vadadustat | Change From Baseline in Red Blood Cell Count | Week 8 | 0.23 10^6 cells per microliter | Standard Deviation 0.351 |
| Vadadustat | Change From Baseline in Red Blood Cell Count | Week 20 | 0.3 10^6 cells per microliter | Standard Deviation 0.411 |
| Vadadustat | Change From Baseline in Red Blood Cell Count | Baseline | 3.38 10^6 cells per microliter | Standard Deviation 0.402 |
| Placebo | Change From Baseline in Red Blood Cell Count | Week 20 | -0.01 10^6 cells per microliter | Standard Deviation 0.314 |
| Placebo | Change From Baseline in Red Blood Cell Count | Baseline | 3.34 10^6 cells per microliter | Standard Deviation 0.322 |
| Placebo | Change From Baseline in Red Blood Cell Count | Week 2 | -0.08 10^6 cells per microliter | Standard Deviation 0.212 |
| Placebo | Change From Baseline in Red Blood Cell Count | Week 4 | -0.08 10^6 cells per microliter | Standard Deviation 0.222 |
| Placebo | Change From Baseline in Red Blood Cell Count | Week 6 | -0.14 10^6 cells per microliter | Standard Deviation 0.276 |
| Placebo | Change From Baseline in Red Blood Cell Count | Week 8 | -0.14 10^6 cells per microliter | Standard Deviation 0.32 |
| Placebo | Change From Baseline in Red Blood Cell Count | Week 12 | -0.08 10^6 cells per microliter | Standard Deviation 0.29 |
| Placebo | Change From Baseline in Red Blood Cell Count | Week 16 | -0.06 10^6 cells per microliter | Standard Deviation 0.331 |
| Placebo | Change From Baseline in Red Blood Cell Count | Week 19 | -0.04 10^6 cells per microliter | Standard Deviation 0.319 |
Comparison: Week 2p-value: =0.0031t-test, 2 sided
Comparison: Week 4p-value: <0.0001t-test, 2 sided
Comparison: Week 6p-value: <0.0001t-test, 2 sided
Comparison: Week 8p-value: <0.0001t-test, 2 sided
Comparison: Week 12p-value: <0.0001t-test, 2 sided
Comparison: Week 16p-value: <0.0001t-test, 2 sided
Comparison: Week 19p-value: <0.0001t-test, 2 sided
Comparison: Week 20p-value: <0.0001t-test, 2 sided
Secondary
Change From Baseline in Reticulocyte Count
Blood samples were collected to assess reticulocyte count. Baseline was defined as mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated reticulocyte count increased.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Change From Baseline in Reticulocyte Count | Week 2 | 0.61 10^6 cells per microliter | Standard Deviation 0.778 |
| Vadadustat | Change From Baseline in Reticulocyte Count | Week 12 | -0.12 10^6 cells per microliter | Standard Deviation 0.742 |
| Vadadustat | Change From Baseline in Reticulocyte Count | Week 6 | 0.19 10^6 cells per microliter | Standard Deviation 0.749 |
| Vadadustat | Change From Baseline in Reticulocyte Count | Week 16 | 0.03 10^6 cells per microliter | Standard Deviation 0.678 |
| Vadadustat | Change From Baseline in Reticulocyte Count | Week 4 | 0.29 10^6 cells per microliter | Standard Deviation 0.686 |
| Vadadustat | Change From Baseline in Reticulocyte Count | Week 19 | 0.07 10^6 cells per microliter | Standard Deviation 0.88 |
| Vadadustat | Change From Baseline in Reticulocyte Count | Week 8 | -0.08 10^6 cells per microliter | Standard Deviation 0.737 |
| Vadadustat | Change From Baseline in Reticulocyte Count | Week 20 | 0.03 10^6 cells per microliter | Standard Deviation 0.666 |
| Vadadustat | Change From Baseline in Reticulocyte Count | Baseline | 2.12 10^6 cells per microliter | Standard Deviation 0.858 |
| Placebo | Change From Baseline in Reticulocyte Count | Week 20 | 0.12 10^6 cells per microliter | Standard Deviation 0.786 |
| Placebo | Change From Baseline in Reticulocyte Count | Baseline | 1.97 10^6 cells per microliter | Standard Deviation 0.816 |
| Placebo | Change From Baseline in Reticulocyte Count | Week 2 | -0.07 10^6 cells per microliter | Standard Deviation 0.532 |
| Placebo | Change From Baseline in Reticulocyte Count | Week 4 | 0.06 10^6 cells per microliter | Standard Deviation 0.485 |
| Placebo | Change From Baseline in Reticulocyte Count | Week 6 | 0.08 10^6 cells per microliter | Standard Deviation 0.549 |
| Placebo | Change From Baseline in Reticulocyte Count | Week 8 | 0.06 10^6 cells per microliter | Standard Deviation 0.665 |
| Placebo | Change From Baseline in Reticulocyte Count | Week 12 | 0.02 10^6 cells per microliter | Standard Deviation 0.639 |
| Placebo | Change From Baseline in Reticulocyte Count | Week 16 | -0.03 10^6 cells per microliter | Standard Deviation 0.659 |
| Placebo | Change From Baseline in Reticulocyte Count | Week 19 | -0.05 10^6 cells per microliter | Standard Deviation 0.672 |
Comparison: Week 2p-value: <0.0001t-test, 2 sided
Comparison: Week 4p-value: =0.0133t-test, 2 sided
Comparison: Week 6p-value: =0.3053t-test, 2 sided
Comparison: Week 8p-value: =0.1918t-test, 2 sided
Comparison: Week 12p-value: =0.209t-test, 2 sided
Comparison: Week 16p-value: =0.6184t-test, 2 sided
Comparison: Week 19p-value: =0.3604t-test, 2 sided
Comparison: Week 20p-value: =0.4056t-test, 2 sided
Secondary
Mean Number of ESA Rescue Doses Administered Per Participant
Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.
Time frame: Up to 20 Weeks
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vadadustat | Mean Number of ESA Rescue Doses Administered Per Participant | Epoetin Alfa | 1.7 Doses/participants | Standard Deviation 1.63 |
| Placebo | Mean Number of ESA Rescue Doses Administered Per Participant | Epoetin Alfa | 2.8 Doses/participants | Standard Deviation 1.79 |
| Placebo | Mean Number of ESA Rescue Doses Administered Per Participant | Darbepoetin Alfa | 4.3 Doses/participants | Standard Deviation 2.52 |
Secondary
Number of Packed Red Blood Cell Transfusion Administered Per Participant
Participants were administered packed red blood cells as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.
Time frame: Up to 20 Weeks
Population: MITT Population. Only participants who received transfusion rescue were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Number of Packed Red Blood Cell Transfusion Administered Per Participant | 1.0 Units of blood per participant |
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 20 Weeks
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat | Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings | 1 Participants |
| Placebo | 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, serum chemistry, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time frame: Up to 20 Weeks
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | Serum chemistry | 1 Participants |
| Vadadustat | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | Hematology | 0 Participants |
| Vadadustat | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | Urinalysis | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | Hematology | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | Serum chemistry | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | Urinalysis | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings
A Baseline physical examination was performed at screening. Otherwise, abbreviated physical examinations were conducted and were to include heart, lung, and abdomen. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time frame: Up to 20 Weeks
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat | Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
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 20 Weeks
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)
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 20 Weeks
Population: Intent-to-treat (ITT) population included all randomized participants who received at least one dose of study medication
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vadadustat | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) | TEAEs | 58 Participants |
| Vadadustat | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) | Treatment-emergent SAEs | 33 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) | TEAEs | 29 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) | Treatment-emergent SAEs | 11 Participants |
Secondary
Percentage of Participants Achieving a Successful Hemoglobin Response, Analyzed in mITT Population
Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Analysis of this secondary outcome measure was performed in the mITT population.
Time frame: Weeks 19 and 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vadadustat | Percentage of Participants Achieving a Successful Hemoglobin Response, Analyzed in mITT Population | 44.1 Percentage of participants |
| Placebo | Percentage of Participants Achieving a Successful Hemoglobin Response, Analyzed in mITT Population | 11.1 Percentage of participants |
p-value: <0.0001Fisher Exact
Secondary
Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value
Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing). Analysis of this secondary outcome measure is a reanalysis of the primary outcome measure whereby the response was determined solely by the Hgb value and receiving rescue therapy did not make the participant a failure.
Time frame: Weeks 19 and 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vadadustat | Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value | 44.9 Percentage of participants |
| Placebo | Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value | 13.9 Percentage of participants |
p-value: <0.0001Fisher Exact
Secondary
Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Actively Treated Group
Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Actively Treated group, defined as participants who had been actively treated with an ESA for a minimum of 4 months before screening, had received at least 2 doses within the last 4 months, had received their last dose within 6 weeks before screening, and had a screening Hgb level ≥9.5 g/dL and ≤12.0 g/dL.
Time frame: Weeks 19 and 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vadadustat | Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Actively Treated Group | 33.3 Percentage of participants |
| Placebo | Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Actively Treated Group | 7.7 Percentage of participants |
p-value: =0.1238Fisher Exact
Secondary
Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Previously Treated Group
Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Previously Treated group, defined as participants who had previously received ≥1 dose of an ESA, had been off of ESA therapy for ≥11 weeks at the time of screening, and had a screening Hgb level of ≤10.5 g/dL.
Time frame: Weeks 19 and 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vadadustat | Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Previously Treated Group | 41.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Previously Treated Group | 19 Percentage of participants |
p-value: =0.0953Fisher Exact
Secondary
Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Treatment naïve Group
Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Treatment Naïve group, defined as participants who had never received treatment with an ESA and who had a screening Hgb level of ≤10.5 g/dL.
Time frame: Weeks 19 and 20
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vadadustat | Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Treatment naïve Group | 50 Percentage of participants |
| Placebo | Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Treatment naïve Group | 7.9 Percentage of participants |
Secondary
Percentage of Participants Who Received ESA Rescue
Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.
Time frame: Up to 20 Weeks
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vadadustat | Percentage of Participants Who Received ESA Rescue | Epoetin Alfa | 4.4 Percentage of participants |
| Vadadustat | Percentage of Participants Who Received ESA Rescue | Darbepoetin Alfa | 0 Percentage of participants |
| Placebo | Percentage of Participants Who Received ESA Rescue | Epoetin Alfa | 12.5 Percentage of participants |
| Placebo | Percentage of Participants Who Received ESA Rescue | Darbepoetin Alfa | 4.2 Percentage of participants |
Secondary
Percentage of Participants Who Received Packed Red Blood Cell Transfusion Rescue
Participants were administered packed red blood cell transfusion as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia
Time frame: Up to 20 Weeks
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vadadustat | Percentage of Participants Who Received Packed Red Blood Cell Transfusion Rescue | 0 Percentage of participants |
| Placebo | Percentage of Participants Who Received Packed Red Blood Cell Transfusion Rescue | 1.4 Percentage of participants |
Secondary
Percentage of Participants With Hemoglobin Value ≥13.0 g/dL at Any Time During the Study
Participants who have experienced an excursion in Hgb to ≥13.0 g/dL at any time during the study were considered as failures. Data was presented for failures.
Time frame: Up to 20 Weeks
Population: Modified Intent-to-Treat (MITT) Population: all randomized participants who received at least one dose of study medication and had a Baseline (either screening or Baseline for both Hgb and RBC count) and at least one post-Baseline measurement for both Hgb and RBC. Only participants with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vadadustat | Percentage of Participants With Hemoglobin Value ≥13.0 g/dL at Any Time During the Study | 59.6 Percentage of participants |
| Placebo | Percentage of Participants With Hemoglobin Value ≥13.0 g/dL at Any Time During the Study | 88.9 Percentage of participants |
p-value: <0.0001Fisher Exact
Secondary
Time to First Transfusion or ESA Rescue Medication Intake
Rescue therapy was defined as red blood cell transfusion or ESA administration in participants meeting Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.
Time frame: Up to 20 Weeks
Population: MITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vadadustat | Time to First Transfusion or ESA Rescue Medication Intake | 21.6 Weeks | Standard Deviation 6.08 |
| Placebo | Time to First Transfusion or ESA Rescue Medication Intake | 21.2 Weeks | Standard Deviation 5.71 |
p-value: =0.001795% CI: [1.5752, 10.908]Log Rank
Other Pre-specified
Exploratory: Absolute Values of Hemoglobin A1c
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Absolute Values of Hepcidin
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Absolute Values of Interleukin 6, Cystatin C, Intact Parathyroid Hormone, and Calcitonin
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Absolute Values of Iron and Total Iron Binding Capacity (TIBC)
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Absolute Values of Lipids
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Absolute Values of Reticulocyte Hemoglobin Content
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Absolute Values of Transferrin
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Absolute Values of Transferrin Saturation
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Change From Baseline in Hemoglobin A1c
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Change From Baseline in Hepcidin
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Change From Baseline in Interleukin 6, Cystatin C, Intact Parathyroid Hormone, and Calcitonin
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Change From Baseline in Iron and Total Iron Binding Capacity (TIBC)
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Change From Baseline in Lipids
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Change From Baseline in Reticulocyte Hemoglobin Content
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Change From Baseline in Transferrin
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Change From Baseline in Transferrin Saturation
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Change From Baseline in Vascular Endothelial Growth Factor (VEGF)
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Mean Weekly Dose of Intravenous Elemental Iron Administered
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Neurocognitive Functioning as a Measure
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Patient-Reported Outcome Measures
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Plasma Concentrations of Vadadustat and Its Glucuronide Metabolites
Time frame: Baseline and up to Week 20
Other Pre-specified
Exploratory: Plasma Concentrations of Vadadustat and Its Glucuronide Metabolites
Time frame: Baseline