Anemia, Dialysis-dependent Chronic Kidney Disease
Conditions
Keywords
Vadadustat, AKB-6548, Anemia, Chronic kidney disease (CKD), erythropoietin
Brief summary
This is a Phase 2 open-label efficacy, safety, and pharmacokinetic/pharmacodynamic (PK/PD) study to evaluate oral Vadadustat for the treatment of anemia in hemodialysis participants converting from Epoetin Alfa therapy.
Detailed description
This is a Phase 2, randomized, open-label study to evaluate efficacy and safety of oral Vadadustat for the treatment of anemia in hemodialysis participants converting from Epoetin Alfa therapy. The study will be conducted in two parts running in parallel: Part 1, Main Study in a hemodialysis population on maintenance treatment with Epoetin Alfa; Part 2 is in a hemodialysis population that are erythropoiesis-stimulating agent (ESA) hyporesponders on maintenance treatment with Epoetin Alfa. For all participants (Main and ESA hyporesponder parallel study), the study will include a Screening Period, a Treatment Period, and a Safety Follow-Up Period. PK and PD sampling will be done throughout the study. The aim is to achieve and maintain hemoglobin (Hb) levels within the target range of 10.0 to 11.0 grams per deciliter (g/dL), inclusive, while targeting the middle of the range and minimizing excursions outside the target range.
Interventions
DRUGVadadustat
Vadadustat Tablets 150 mg
DRUGEpoetin Alfa
Epoetin Alfa
DRUGVadadustat TIW
Oral Vadadustat
Sponsors
Akebia Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized, Open-Label, Active-Controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* ≥18 years of age, providing informed consent * Receiving chronic, outpatient in-center hemodialysis (TIW) for end-stage renal disease for at least 12 weeks prior to Screening * Maintained on intravenous Epoetin Alfa therapy for 8 weeks prior to and including Screening through Screening Visit 2 (SV2) * Eligibility in the Main study and erythropoiesis-stimulating agent (ESA) hyporesponder parallel study is based on the following mean weekly Epoetin Alfa doses: 1. Main study: Mean weekly Epoetin Alfa dose \<300 Units per kilogram per week (U/kg/week) for 8 weeks prior to SV2; 2. ESA hyporesponder parallel study: Mean weekly Epoetin Alfa dose ≥300 U/kg/week for 8 weeks prior to SV2 * Two Hb values measured by the central laboratory at least 4 days apart between Screening Visit 1 (SV1) and SV2 as indicated:. 1. Main study: 2 Hb values between 8.5 and 11.0 g/dL, inclusive; 2. ESA hyporesponder parallel study: 2 Hb values between 8.0 and 10.0 grams per deciliter (g/dL), inclusive * Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening * Folate and vitamin B12 measurements ≥ lower limit of normal during Screening * Hemodialysis adequacy as indicated by single-pool Kt/Vurea ≥1.2 using the most recent historical measurement within 8 weeks prior to or during Screening * Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure
Exclusion criteria
* Anemia due to a cause other than chronic kidney disease (e.g., sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia) * Active bleeding or recent blood loss within 8 weeks prior to randomization * Red blood cell (RBC) transfusion within 8 weeks prior to randomization * Anticipated to discontinue hemodialysis during the study * Judged by the Investigator that the participant is likely to need rescue therapy (ESA administration or RBC transfusion) immediately after enrollment in the study * History of chronic liver disease (e.g., chronic infectious hepatitis, chronic autoimmune liver disease, cirrhosis or fibrosis of the liver) * Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT), or total bilirubin \>1.5 x upper limit of normal (ULN) during Screening. Participants with a history of Gilbert's syndrome are not excluded. * Current uncontrolled hypertension as determined by the Investigator that would contraindicate the use of Epoetin Alfa * Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure (HF) or New York Heart Association Class IV HF, or stroke within 12 weeks prior to or during Screening * History of new or recurrent malignancy within 2 years prior to and during Screening or currently receiving treatment or suppressive therapy for cancer. Participants with treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma of skin, or cervical carcinoma in situ are not excluded. * History of deep vein thrombosis or pulmonary embolism within 12 weeks prior to or during Screening * History of hemosiderosis or hemochromatosis * History of prior organ transplantation (participants with a history of failed kidney transplant or corneal transplants are not excluded) * Scheduled organ transplant from a living donor and participants on the kidney transplant wait-list who are expected to receive a transplant within 6 months * History of a prior hematopoietic stem cell or bone marrow transplant (stem cell therapy for knee arthritis is not excluded) * Known hypersensitivity to Vadadustat, Epoetin Alfa, or any of their excipients * Any prior use of a hypoxia-inducible factor prolyl-hydroxylase (HIF-PH) inhibitor or any use of an investigational medication within 30 days or 5 half-lives of the investigational medication (whichever is longer), prior to randomization * For female participants of non-childbearing potential: 1. inability to confirm surgical sterility (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy) at least 1 month prior to Screening; 2. not considered post-menopausal (no menses for \>1 year with follicle stimulating hormone \>40 U/Liter at Screening) * For female participants of childbearing potential: 1. lack of confirmation of the use of acceptable forms of contraception\* for a minimum of one complete menstrual cycle prior to Screening; 2. positive serum pregnancy test at SV2; 3. unwilling to use two acceptable forms of contraception\* (at least one of which must be a barrier method) starting Baseline/Day 1, throughout the Treatment Period and for 30 days after the final study drug administration * Breastfeeding during Screening or throughout the Treatment Period and for 30 days after the final study drug administration * Donation of ova starting at Screening, throughout the Treatment Period, and for 30 days after the final study drug administration * Male participants who have not had a vasectomy and do not agree to the following: use of an acceptable form of contraception\* during the study and for 30 days after the last dose of the study drug; to not donate semen during the study and for at least 30 days after the last dose of Vadadustat * Participants with bilateral native nephrectomy * Any other reason, which in the opinion of the Investigator, would make the participant not suitable for participation in the study * Acceptable forms of contraception include: * Established use of oral, injected or implanted hormonal methods of contraception; * Placement of an intrauterine device or intrauterine system; * Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Baseline; Week 10 to Week 12 | Change from Baseline in Hb value was calculated as the PEP Hb value minus the Baseline Hb value. The PEP value was the average Hb value from Week 10 to Week 12. The Baseline Hb value was defined as the average of the final two Hb values prior to start of dosing on Day 1. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to Week 24 | An adverse event (AE) was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. An AE included medical conditions, signs, and symptoms not previously observed in the participant that emerged during the protocol-specified AE reporting period, including signs or symptoms associated with pre-existing underlying conditions that were not present prior to the AE reporting period. TEAEs, defined as AEs that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, are reported. |
| Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | Up to Week 24 | Parameters assessed for laboratory values included hematology (excluding the primary and secondary efficacy endpoint results related to Hb), clinical chemistry, lipid profiles, and glucose. 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 Week 24 | 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 vital sign values for clinically significant changes. |
| Number of Participants Classified as Hb Outliers | Weeks 13 - 20 | The target range for Hb was from 10.0 to 11.0 grams per deciliter (g/dL). Hb outliers included participants with a Hb increase of more than 12.0 g/dL or \<8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline, and a Hb increase to more than 1.0 g/dL within any 2-week interval during the Study Period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Hepcidin Concentration | Baseline; Week 12 and Week 20 | Blood samples were collected from participants at defined time points for the assessment of hepcidin concentration. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose | Blood samples were collected from participants at defined time points for the assessment of Cmax of Vadadustat following a single dose. |
| Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Day 1; Week 1, Week 1 +1 (Day 8), Week 11: pre-dose, 2h, 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose | Blood samples were collected from participants at defined time points for the assessment of AUC and AUC0-24 of Vadadustat following a single dose. |
| Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose | Blood samples were collected from participants at defined time points for the assessment of t1/2 of Vadadustat following a single dose. |
| Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose | Blood samples were collected from participants at defined time points for the assessment of Tmax of Vadadustat following a single dose. |
| Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose | Blood samples were collected from participants at defined time points for the assessment of λz of Vadadustat following a single dose. |
| Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Day 1; Week 1, Week 1 +1 (Day 8), Week 11: pre-dose, 2h, 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose | Blood samples were collected from participants at defined time points for the assessment of CLss/F of Vadadustat following a single dose. |
| Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Day 1; Week 1, Week 1 +1 (Day 8), Week 11: pre-dose, 2h, 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose | Blood samples were collected from participants at defined time points for the assessment of Vz/F of Vadadustat following a single dose. |
| Number of Participants With Hb Values Within the Target Range at the PEP | Week 10 to Week 12 | The target range for Hb was from 10.0 to 11.0 g/dL, inclusive. The PEP was comprised of Week 10 to Week 12. |
| Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Baseline; Week 1 (pre-dose), Week 1 +1 (Day 8; pre-dose), Week 11 (pre-dose), and Week 13 (pre-dose) | Blood samples were collected from participants at defined time points for the assessment of EPO concentration. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Mean Change in Hb Between Baseline and the SEP | Baseline; Week 18 to Week 20 | Change from Baseline was calculated as the SEP value minus the Baseline value. The Baseline Hb value was defined as the average of the final two Hb values prior to start of dosing on Day 1. The SEP value was the average Hb value from Week 18 to Week 20. |
| Number of Participants With Hb Values Within the Target Range at the SEP | Week 18 to Week 20 | The target range for Hb was from 10.0 to 11.0 g/dL. The SEP was comprised of Week 18 to Week 20. |
| Number of Participants With Hb Values Within the Target Range at the SEP in Participants Who Transitioned to TIW Vadadustat Dosing | Week 18 to Week 20 | The target range for Hb was from 10.0 to 11.0 g/dL. The SEP was comprised of Week 18 to Week 20. For the Main Study, analysis is presented per dose level according to the starting dose in TIW regimen, as well as being presented as a combined arm for Vadadustat Total (TIW dosing regimen). For the ESA Hyporesponder Parallel Study, a starting dose classification for TIW dosing regimen was not applicable due to no participants switching from Vadadustat QD to TIW dosing. |
| Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP | Week 10 to Week 12 | The target range for Hb was from 10.0 to 11.0 g/dL. The PEP was comprised of Week 10 to Week 12. |
| Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP | Week 18 to Week 20 | The target range for Hb was from 10.0 to 11.0 grams per g/dL. The SEP was comprised of Week 18 to Week 20. |
| Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation | Up to Week 20 | Iron supplementation was performed to maintain ferritin ≥200 nanograms/milliliters (ng/mL) and transferrin saturation (TSAT) ≥20%. |
| Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue | Up to Week 20 | ESA rescue therapy was administered in participants with Hb ≥8.5 g/dL, and was stopped when Hb reached ≥9.0 g/dL. |
| Number of Participants Requiring Red Blood Cell (RBC) Transfusion | Up to Week 20 | RBC transfusion was administered as rescue therapy in the event of an acute or severe loss of blood. |
| Mean Change in Hb From the PEP to the Secondary Evaluation Period (SEP) in Participants Who Transitioned to Three Times Per Week (TIW) Vadadustat Dosing After Week 12 | Week 10 to Week 12; Week 18 to Week 20 | Change from PEP was calculated as the SEP value minus the PEP value. The PEP value was the average Hb value from Week 10 to Week 12. The SEP value was the average Hb value from Week 18 to Week 20. For the Main Study, analysis is presented per dose level according to the starting dose in TIW regimen, as well as being presented as a combined arm for Vadadustat Total (TIW dosing regimen). For the ESA Hyporesponder Parallel Study, a starting dose classification for TIW dosing regimen was not applicable due to no participants switching from Vadadustat QD to TIW dosing. |
| Mean Change From Baseline in Reticulocyte Count | Baseline; Week 1, Week 4, Week 8, Week 11, Week 12, Week 13, Week 16, and Week 20 | Blood samples were collected from participants at defined time points for the assessment of reticulocyte count. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Mean Change From Baseline in Iron Concentration | Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20 | Blood samples were collected from participants at defined time points for the assessment of iron indices, including iron concentration. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Mean Change From Baseline in Ferritin Concentration | Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20 | Blood samples were collected from participants at defined time points for the assessment of iron indices, including ferritin concentration. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Mean Change From Baseline in Total Iron Binding Capacity | Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20 | Blood samples were collected from participants at defined time points for the assessment of iron indices, including Total Iron Binding Capacity. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
Countries
United States
Participant flow
Pre-assignment details
A total of 540 participants were screened, of which 175 participants were enrolled and randomized into the 2 parts of this study (Main Study; n=165; Erythropoiesis-stimulating Agent (ESA) Hyporesponder Parallel Study: n=10). A total of 365 participants failed screening. Participants were randomized to either a Vadadustat or Epoetin Alfa treatment group, and randomization was stratified by mean weekly Epoetin Alfa dose calculated over a period of 8 weeks prior to Screening Visit 2.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg Participants who were maintained on the low dose of Epoetin Alfa (≤90 units per kilogram per week \[U/kg/week\]) prior to and including the Screening Period for a minimum of 8 weeks prior to Screening Visit 2 were administered an oral dose of Vadadustat 300 milligram (mg) tablet per day (QD) until Week 12. Eligible participants based on investigator's discretion were switched from daily dosing to three times per week (TIW) dosing of the starting Vadadustat dose (300 mg) plus a 150 mg greater dose (450 mg) to maintain target hemoglobin (Hb) levels during Week 12 to Week 14. Non-eligile participants continued with daily dosing. Participants who reported a decline in Hb ≥0.5 grams per deciliter (g/dL) were eligible for a dose increase by another 150 mg until Week 20. | 35 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg Participants who were maintained on the low dose of Epoetin Alfa (≤90 U/kg/week) prior to and including the Screening Period for a minimum of 8 weeks prior to Screening Visit 2 were administered an oral dose of Vadadustat 450 mg tablet QD until Week 12. Eligible participants based on investigator's discretion were switched from daily dosing to TIW dosing of the starting Vadadustat dose (450 mg) plus a 150 mg greater dose (600 mg) to maintain target Hb levels during Week 12 to Week 14. Non-eligible participants continued with daily dosing. Participants who reported a decline in Hb ≥0.5 g/dL were eligible for a dose increase by another 150 mg until Week 20. | 34 |
| Low Dose of Epoetin Alfa: Epoetin Alfa Participants who were maintained on the low dose of Epoetin Alfa (≤90 U/kg/week) prior to and including the Screening Period were administered TIW dosing of Epoetin Alfa for the entire Treatment Period based on the participant's Hb value and the approved Epoetin Alfa United States (US) Package Insert (PI) for adult participants with chronic kidney disease (CKD) on dialysis. The dose was adjusted to achieve and maintain target Hb levels of 10.0-11.0 g/dL, inclusive. | 23 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg Participants who were maintained on the high dose of Epoetin Alfa (\>90 to \<300 U/kg/week) prior to and including the Screening Period for a minimum of 8 weeks prior to Screening Visit 2 were administered an oral dose of Vadadustat 300 mg tablet QD until Week 12. Eligible participants based on investigator's discretion were switched from daily dosing to TIW dosing of the starting Vadadustat dose (300 mg) plus a 150 mg greater dose (450 mg) to maintain target Hb levels during Week 12 to Week 14. Non-eligible participants continued with daily dosing. Participants who reported a decline in Hb ≥0.5 g/dL were eligible for a dose increase by another 150 mg until Week 20. | 18 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg Participants who were maintained on the high dose of Epoetin Alfa (\>90 to \<300 U/kg/week) prior to and including the Screening Period for a minimum of 8 weeks prior to Screening Visit 2 were administered an oral dose of Vadadustat 450 mg tablet QD until Week 12. Eligible participants based on investigator's discretion were switched from daily dosing to TIW dosing of the starting Vadadustat dose (450 mg) plus a 150 mg greater dose (600 mg) to maintain target Hb levels during Week 12 to Week 14. Non-eligible participants continued with daily dosing. Participants who reported a decline in Hb ≥0.5 g/dL were eligible for a dose increase by another 150 mg until Week 20. | 21 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg Participants who were maintained on the high dose of Epoetin Alfa (\>90 to \<300 U/kg/week) prior to and including the Screening Period for a minimum of 8 weeks prior to Screening Visit 2 were administered an oral dose of Vadadustat 600 mg tablet QD until Week 12. Eligible participants based on investigator's discretion were switched from daily dosing to TIW dosing of the starting Vadadustat dose (600 mg) plus a 150 mg greater dose (750 mg) to maintain target Hb levels during Week 12 to Week 14. Non-eligible participants continued with daily dosing. Participants who reported a decline in Hb ≥0.5 g/dL were eligible for a dose increase by another 150 mg until Week 20. | 21 |
| High Dose of Epoetin Alfa: Epoetin Alfa Participants who were maintained on the high dose of Epoetin Alfa (\>90 to \<300 U/kg/week) prior to and including the Screening Period were administered TIW dosing of Epoetin Alfa for the entire Treatment Period based on the participant's Hb value and the approved Epoetin Alfa US PI for adult participants with CKD on dialysis. The dose was adjusted to achieve and maintain target Hb levels of 10.0-11.0 g/dL, inclusive. | 13 |
| ESA Hyporesponder: Vadadustat 600 mg In the Erythropoiesis-stimulating Agent (ESA) Hyporesponder Parallel Study, participants who were maintained on a ≥300 U/kg/week dose of Epoetin Alfa prior to and including the Screening Period for a minimum of 8 weeks prior to Screening Visit 2 were administered an oral dose of Vadadustat 600 mg tablet QD until Week 12. Eligible participants based on investigator's discretion were switched from daily dosing to TIW dosing of the starting Vadadustat dose (600 mg) plus a 150 mg greater dose (750 ng) to maintain target Hb levels during Week 12 to Week 14. Non-eligible participants continued with daily dosing. Participants who reported a decline in Hb ≥0.5 g/dL were eligible for a dose increase by another 150 mg until Week 20. | 5 |
| ESA Hyporesponder: Epoetin Alfa In the ESA Hyporesponder Parallel Study, participants who were maintained on a ≥300 U/kg/week dose of Epoetin Alfa prior to and including the Screening Period for a minimum of 8 weeks prior to Screening Visit 2 were administered TIW dosing of Epoetin Alfa based on the participant's central laboratory Hb value and the approved Epoetin Alfa US PI for adult participants with CKD on dialysis. The dose was adjusted to achieve and maintain target Hb levels of 10.0-11.0 g/dL, inclusive. | 5 |
| Total | 175 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 | 0 | 2 | 5 | 0 | 2 | 0 |
| Overall Study | Changes In Hemoglobin Values | 1 | 2 | 1 | 0 | 0 | 2 | 1 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Due to Urgent Safety Measures Letter | 1 | 2 | 0 | 2 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Eurofin Issue | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Investigational Product Noncompliance | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Kidney Transplantation | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Met Exclusion Criteria | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Noncompliance with Site Instructions | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Participant Relocation | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Participant's Last Dose Prior to End of Treatment | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Participant Was on Rescue Epogen | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Physician Decision | 2 | 2 | 0 | 0 | 2 | 2 | 0 | 0 | 0 |
| Overall Study | Placed on Dose Hold Until End of Treatment | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Study Drug Put on Hold | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 2 | 0 | 3 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Low Dose of Epoetin Alfa: Vadadustat 300 mg | Low Dose of Epoetin Alfa: Vadadustat 450 mg | Low Dose of Epoetin Alfa: Epoetin Alfa | High Dose of Epoetin Alfa: Vadadustat 300 mg | High Dose of Epoetin Alfa: Vadadustat 450 mg | High Dose of Epoetin Alfa: Vadadustat 600 mg | High Dose of Epoetin Alfa: Epoetin Alfa | ESA Hyporesponder: Vadadustat 600 mg | ESA Hyporesponder: Epoetin Alfa | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized <65 years | 20 Participants | 22 Participants | 15 Participants | 11 Participants | 18 Participants | 13 Participants | 7 Participants | 4 Participants | 3 Participants | 113 Participants |
| Age, Customized >=65 years | 15 Participants | 12 Participants | 8 Participants | 7 Participants | 3 Participants | 8 Participants | 6 Participants | 1 Participants | 2 Participants | 62 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 19 Participants | 7 Participants | 8 Participants | 13 Participants | 14 Participants | 6 Participants | 2 Participants | 2 Participants | 89 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 13 Participants |
| Race (NIH/OMB) White | 10 Participants | 9 Participants | 13 Participants | 5 Participants | 6 Participants | 5 Participants | 5 Participants | 3 Participants | 0 Participants | 56 Participants |
| Sex: Female, Male Female | 14 Participants | 13 Participants | 4 Participants | 7 Participants | 7 Participants | 9 Participants | 6 Participants | 4 Participants | 3 Participants | 67 Participants |
| Sex: Female, Male Male | 21 Participants | 21 Participants | 19 Participants | 11 Participants | 14 Participants | 12 Participants | 7 Participants | 1 Participants | 2 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 35 | 0 / 23 | 1 / 18 | 1 / 21 | 1 / 21 | 1 / 13 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 11 / 34 | 20 / 35 | 10 / 23 | 9 / 18 | 9 / 21 | 10 / 21 | 8 / 13 | 4 / 5 | 2 / 5 |
| serious Total, serious adverse events | 9 / 34 | 7 / 35 | 5 / 23 | 8 / 18 | 6 / 21 | 10 / 21 | 5 / 13 | 4 / 5 | 3 / 5 |
Outcome results
Primary
Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP)
Change from Baseline in Hb value was calculated as the PEP Hb value minus the Baseline Hb value. The PEP value was the average Hb value from Week 10 to Week 12. The Baseline Hb value was defined as the average of the final two Hb values prior to start of dosing on Day 1.
Time frame: Baseline; Week 10 to Week 12
Population: Randomized Population: All randomized participants. Analysis of this population was based on the randomized treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Baseline | 10.223 grams per deciliter (g/dL) | Standard Deviation 0.5805 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Change from Baseline at PEP | -0.371 grams per deciliter (g/dL) | Standard Deviation 0.892 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Baseline | 10.059 grams per deciliter (g/dL) | Standard Deviation 0.6769 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Change from Baseline at PEP | 0.072 grams per deciliter (g/dL) | Standard Deviation 1.1353 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Baseline | 10.165 grams per deciliter (g/dL) | Standard Deviation 0.6806 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Change from Baseline at PEP | 0.160 grams per deciliter (g/dL) | Standard Deviation 0.7519 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Baseline | 9.778 grams per deciliter (g/dL) | Standard Deviation 0.6832 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Change from Baseline at PEP | -0.911 grams per deciliter (g/dL) | Standard Deviation 1.3515 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Baseline | 10.288 grams per deciliter (g/dL) | Standard Deviation 0.5445 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Change from Baseline at PEP | -0.284 grams per deciliter (g/dL) | Standard Deviation 1.0383 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Change from Baseline at PEP | -0.418 grams per deciliter (g/dL) | Standard Deviation 1.2752 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Baseline | 10.095 grams per deciliter (g/dL) | Standard Deviation 0.715 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Change from Baseline at PEP | 0.268 grams per deciliter (g/dL) | Standard Deviation 1.0087 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Baseline | 9.950 grams per deciliter (g/dL) | Standard Deviation 0.795 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Baseline | 9.530 grams per deciliter (g/dL) | Standard Deviation 0.2864 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Change from Baseline at PEP | -0.671 grams per deciliter (g/dL) | Standard Deviation 0.7643 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Baseline | 9.620 grams per deciliter (g/dL) | Standard Deviation 0.6925 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change in Hemoglobin (Hb) Between Baseline and the Primary Evaluation Period (PEP) | Change from Baseline at PEP | -0.290 grams per deciliter (g/dL) | Standard Deviation 1.773 |
Primary
Number of Participants Classified as Hb Outliers
The target range for Hb was from 10.0 to 11.0 grams per deciliter (g/dL). Hb outliers included participants with a Hb increase of more than 12.0 g/dL or \<8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline, and a Hb increase to more than 1.0 g/dL within any 2-week interval during the Study Period.
Time frame: Weeks 13 - 20
Population: Safety Population. Analysis of this population was based on the actual treatment received. Participants who received Vadadustat and Epoetin Alfa in error were classified by the more frequently received drug. Only participants with available data were included in the analysis. The rows presenting data for HB \> 12.0 g/dL, HB \> 13.0 g/dL and HB \> 14.0 g/dL are mutually exclusive.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Classified as Hb Outliers | Hb >13.0 g/dL | 1 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Classified as Hb Outliers | Hb increase >1.0 g/dL within any 2-week interval | 4 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Classified as Hb Outliers | Hb <8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline | 2 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Classified as Hb Outliers | Hb >14.0 g/dL | 1 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Classified as Hb Outliers | Hb >12.0 g/dL | 2 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Classified as Hb Outliers | Hb >14.0 g/dL | 0 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Classified as Hb Outliers | Hb >12.0 g/dL | 2 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Classified as Hb Outliers | Hb increase >1.0 g/dL within any 2-week interval | 8 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Classified as Hb Outliers | Hb >13.0 g/dL | 0 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Classified as Hb Outliers | Hb <8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline | 2 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb <8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline | 0 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb >14.0 g/dL | 1 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb >12.0 g/dL | 3 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb increase >1.0 g/dL within any 2-week interval | 4 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb >13.0 g/dL | 1 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Classified as Hb Outliers | Hb increase >1.0 g/dL within any 2-week interval | 4 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Classified as Hb Outliers | Hb >13.0 g/dL | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Classified as Hb Outliers | Hb <8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline | 1 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Classified as Hb Outliers | Hb >12.0 g/dL | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Classified as Hb Outliers | Hb >14.0 g/dL | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Classified as Hb Outliers | Hb >14.0 g/dL | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Classified as Hb Outliers | Hb >12.0 g/dL | 1 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Classified as Hb Outliers | Hb >13.0 g/dL | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Classified as Hb Outliers | Hb <8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline | 1 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Classified as Hb Outliers | Hb increase >1.0 g/dL within any 2-week interval | 2 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants Classified as Hb Outliers | Hb >13.0 g/dL | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants Classified as Hb Outliers | Hb >14.0 g/dL | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants Classified as Hb Outliers | Hb <8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline | 3 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants Classified as Hb Outliers | Hb increase >1.0 g/dL within any 2-week interval | 3 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants Classified as Hb Outliers | Hb >12.0 g/dL | 0 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb >14.0 g/dL | 0 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb >13.0 g/dL | 0 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb >12.0 g/dL | 1 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb <8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline | 1 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb increase >1.0 g/dL within any 2-week interval | 6 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants Classified as Hb Outliers | Hb >14.0 g/dL | 0 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants Classified as Hb Outliers | Hb >13.0 g/dL | 0 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants Classified as Hb Outliers | Hb increase >1.0 g/dL within any 2-week interval | 0 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants Classified as Hb Outliers | Hb <8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline | 1 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants Classified as Hb Outliers | Hb >12.0 g/dL | 0 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb increase >1.0 g/dL within any 2-week interval | 2 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb >12.0 g/dL | 0 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb <8.0 g/dL and decline in Hb ≥0.5 g/dL from Baseline | 1 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb >13.0 g/dL | 0 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants Classified as Hb Outliers | Hb >14.0 g/dL | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Parameters assessed for laboratory values included hematology (excluding the primary and secondary efficacy endpoint results related to Hb), clinical chemistry, lipid profiles, and glucose. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time frame: Up to Week 24
Population: Safety Population. Analysis of this population was based on the actual treatment received. Participants who received Vadadustat and Epoetin Alfa in error were classified by the more frequently received drug. One participant randomized to the Low Dose of Epoetin Alfa: Vadadustat 300 mg arm inadvertently received 450 mg of Vadadustat.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
Primary
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 vital sign values for clinically significant changes.
Time frame: Up to Week 24
Population: Safety Population. Analysis of this population was based on the actual treatment received. Participants who received Vadadustat and Epoetin Alfa in error were classified by the more frequently received drug. One participant randomized to the Low Dose of Epoetin Alfa: Vadadustat 300 mg arm inadvertently received 450 mg of Vadadustat.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values | 0 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values | 0 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values | 0 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values | 0 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values | 0 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Values | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. An AE included medical conditions, signs, and symptoms not previously observed in the participant that emerged during the protocol-specified AE reporting period, including signs or symptoms associated with pre-existing underlying conditions that were not present prior to the AE reporting period. TEAEs, defined as AEs that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, are reported.
Time frame: Up to Week 24
Population: Safety Population: all participants in the Randomized Population who received at least 1 dose of study drug. Analysis of this population was based on actual treatment received. Participants who received Vadadustat and Epoetin Alfa in error were classified by the more frequently received drug. One participant randomized to the Low Dose of Epoetin Alfa: Vadadustat 300 mg arm inadvertently received 450 mg of Vadadustat.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 18 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 27 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 13 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 12 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 14 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 13 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 9 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
Secondary
Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of CLss/F of Vadadustat following a single dose.
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11: pre-dose, 2h, 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Population: PK Population. Analysis of this population was based on the dose amount taken at the date of PK sampling for the Vadadustat group. Participants with non-missing values were included in the analysis. PK parameter of plasma Vadadustat concentration for Vadadustat treatment groups without dose normalization by strata of Epoetin Alfa dose group were included for the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 1 | 0.888 liters per hour | Geometric Coefficient of Variation 63.8 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 1.04 liters per hour | Geometric Coefficient of Variation 76.6 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 11 | 0.872 liters per hour | Geometric Coefficient of Variation 53.5 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 0.967 liters per hour | Geometric Coefficient of Variation 80.8 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 1 | 0.869 liters per hour | Geometric Coefficient of Variation 71.1 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 11 | 1.33 liters per hour | Geometric Coefficient of Variation 282 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 0.968 liters per hour | Geometric Coefficient of Variation 94.7 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 11 | 0.747 liters per hour | Geometric Coefficient of Variation 70.8 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 1 | 0.877 liters per hour | Geometric Coefficient of Variation 81.7 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 1 | 0.744 liters per hour | Geometric Coefficient of Variation 54.5 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 11 | 1.00 liters per hour | Geometric Coefficient of Variation 68.2 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 0.795 liters per hour | Geometric Coefficient of Variation 41.1 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 11 | 1.02 liters per hour | Geometric Coefficient of Variation 52.5 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 1 | 0.763 liters per hour | Geometric Coefficient of Variation 36.6 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 0.708 liters per hour | Geometric Coefficient of Variation 54.8 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 1.55 liters per hour | Geometric Coefficient of Variation 112.4 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Geometric Mean Apparent Total Body Clearance (CLss/F) of Vadadustat Following a Single Dose | Week 1 | 1.29 liters per hour | Geometric Coefficient of Variation 80.9 |
Secondary
Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of Vz/F of Vadadustat following a single dose.
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11: pre-dose, 2h, 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Population: PK Population. Analysis of this population was based on the dose amount taken at the date of PK sampling for the Vadadustat group. Participants with non-missing values were included in the analysis. PK parameter of plasma Vadadustat concentration for Vadadustat treatment groups without dose normalization by strata of Epoetin Alfa dose group were included for the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 12.5 Liters | Geometric Coefficient of Variation 36.6 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 11 | 10.2 Liters | Geometric Coefficient of Variation 28.7 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 1 | 10.9 Liters | Geometric Coefficient of Variation 36.2 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 13.7 Liters | Geometric Coefficient of Variation 41 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 1 | 14.3 Liters | Geometric Coefficient of Variation 53.4 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 11 | 10.7 Liters | Geometric Coefficient of Variation 37.6 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 17.4 Liters | Geometric Coefficient of Variation 50.4 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 1 | 13.7 Liters | Geometric Coefficient of Variation 69.7 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 11 | 10.1 Liters | Geometric Coefficient of Variation 10.3 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 15.3 Liters | Geometric Coefficient of Variation 67.4 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 1 | 12.1 Liters | Geometric Coefficient of Variation 38.6 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 11 | 8.24 Liters | — |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 1 | 13.8 Liters | Geometric Coefficient of Variation 16.7 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 11 | 8.76 Liters | Geometric Coefficient of Variation 18.9 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 15.6 Liters | Geometric Coefficient of Variation 27.2 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 1 | 15.8 Liters | Geometric Coefficient of Variation 56.9 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Geometric Mean Apparent Volume of Distribution (Vz/F) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 12.4 Liters | Geometric Coefficient of Variation 35.8 |
Secondary
Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of AUC and AUC0-24 of Vadadustat following a single dose.
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11: pre-dose, 2h, 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Population: PK Population. Analysis of this population was based on the dose amount taken at the date of PK sampling for the Vadadustat group. Participants with non-missing values were included in the analysis. PK parameter of plasma Vadadustat concentration for Vadadustat treatment groups without dose normalization by strata of Epoetin Alfa dose group were included for the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 289 hours*µg/mL | Geometric Coefficient of Variation 76.6 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 11 | 344 hours*µg/mL | Geometric Coefficient of Variation 53.5 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 1 | 338 hours*µg/mL | Geometric Coefficient of Variation 63.8 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 465 hours*µg/mL | Geometric Coefficient of Variation 80.8 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 1 | 518 hours*µg/mL | Geometric Coefficient of Variation 71.1 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 11 | 338 hours*µg/mL | Geometric Coefficient of Variation 282 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 310 hours*µg/mL | Geometric Coefficient of Variation 94.7 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 1 | 342 hours*µg/mL | Geometric Coefficient of Variation 81.7 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 11 | 402 hours*µg/mL | Geometric Coefficient of Variation 70.8 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 566 hours*µg/mL | Geometric Coefficient of Variation 41.1 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 1 | 605 hours*µg/mL | Geometric Coefficient of Variation 54.5 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 11 | 450 hours*µg/mL | Geometric Coefficient of Variation 68.2 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 1 | 786 hours*µg/mL | Geometric Coefficient of Variation 36.6 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 11 | 588 hours*µg/mL | Geometric Coefficient of Variation 52.5 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 847 hours*µg/mL | Geometric Coefficient of Variation 54.8 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 1 | 464 hours*µg/mL | Geometric Coefficient of Variation 80.9 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Geometric Mean Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 388 hours*µg/mL | Geometric Coefficient of Variation 112.4 |
Secondary
Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of λz of Vadadustat following a single dose.
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Population: PK Population. Analysis of this population was based on the dose amount taken at the date of PK sampling for the Vadadustat group. Participants with non-missing values were included in the analysis. PK parameter of plasma Vadadustat concentration for Vadadustat treatment groups without dose normalization by strata of Epoetin Alfa dose group were included for the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 11 | 0.0925 1/hour | Geometric Coefficient of Variation 65.5 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 1 | 0.0797 1/hour | Geometric Coefficient of Variation 38.7 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 0.0720 1/hour | Geometric Coefficient of Variation 44.2 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 11 | 0.0687 1/hour | Geometric Coefficient of Variation 26.5 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 1 | 0.0665 1/hour | Geometric Coefficient of Variation 50.5 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 13 | 0.0632 1/hour | — |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 0.0615 1/hour | Geometric Coefficient of Variation 70 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 1 | 0.0560 1/hour | Geometric Coefficient of Variation 41.6 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 0.0714 1/hour | Geometric Coefficient of Variation 53.9 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 11 | 0.124 1/hour | Geometric Coefficient of Variation 92 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 0.0469 1/hour | Geometric Coefficient of Variation 72.2 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 1 | 0.0681 1/hour | Geometric Coefficient of Variation 32.7 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 11 | 0.175 1/hour | — |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 0.0469 1/hour | Geometric Coefficient of Variation 74.4 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 13 | 0.138 1/hour | — |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 11 | 0.116 1/hour | Geometric Coefficient of Variation 15.9 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 1 | 0.0608 1/hour | Geometric Coefficient of Variation 46.9 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 1 | 0.0771 1/hour | Geometric Coefficient of Variation 8.9 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Geometric Mean Elimination Rate Constant (λz) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 0.0594 1/hour | Geometric Coefficient of Variation 4.5 |
Secondary
Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of Cmax of Vadadustat following a single dose.
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Population: PK Population. Analysis of this population was based on the dose amount taken at the date of PK sampling for the Vadadustat group. Participants with non-missing values were included in the analysis. PK parameter of plasma Vadadustat concentration for Vadadustat treatment groups without dose normalization by strata of Epoetin Alfa dose group were included for the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 11 | 28.6 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 49.3 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 20.1 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 174.4 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 1 | 26.0 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 87.9 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 11 | 24.4 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 350.6 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 13 | 30.6 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 102.7 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 1 | 40.8 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 54.8 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 37.6 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 78.9 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 1 | 26.5 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 59.3 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 23.8 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 69 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 11 | 32.4 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 26.9 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 13 | 11.5 Micrograms per milliliter (μg/mL) | — |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 1 | 47.0 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 38.2 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 44.2 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 29.6 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 11 | 38.1 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 99 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 13 | 60.2 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 9.2 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 1 | 56.5 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 39.2 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 60.1 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 41.6 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 11 | 41.2 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 77.7 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 31.6 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 151.6 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Vadadustat Following a Single Dose | Week 1 | 44.2 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 73.1 |
Secondary
Mean Change From Baseline in Ferritin Concentration
Blood samples were collected from participants at defined time points for the assessment of iron indices, including ferritin concentration. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Participants with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Ferritin Concentration | Week 8 | -120.8 micrograms per liter (µg/L) | Standard Deviation 273.28 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Ferritin Concentration | Week 20 | -113.6 micrograms per liter (µg/L) | Standard Deviation 327.06 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Ferritin Concentration | Week 4 | -30.1 micrograms per liter (µg/L) | Standard Deviation 185.45 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Ferritin Concentration | Baseline | 939.3 micrograms per liter (µg/L) | Standard Deviation 478.64 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Ferritin Concentration | Week 16 | -92.0 micrograms per liter (µg/L) | Standard Deviation 309.88 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Ferritin Concentration | Week 12 | -118.5 micrograms per liter (µg/L) | Standard Deviation 220.4 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Ferritin Concentration | Week 20 | -166.6 micrograms per liter (µg/L) | Standard Deviation 298.67 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Ferritin Concentration | Week 16 | -70.9 micrograms per liter (µg/L) | Standard Deviation 288.34 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Ferritin Concentration | Week 4 | -101.9 micrograms per liter (µg/L) | Standard Deviation 204.51 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Ferritin Concentration | Week 12 | -194.8 micrograms per liter (µg/L) | Standard Deviation 288.47 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Ferritin Concentration | Week 8 | -185.4 micrograms per liter (µg/L) | Standard Deviation 298.19 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Ferritin Concentration | Baseline | 1043.6 micrograms per liter (µg/L) | Standard Deviation 359.1 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 8 | 24.9 micrograms per liter (µg/L) | Standard Deviation 334.28 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 16 | 99.5 micrograms per liter (µg/L) | Standard Deviation 567.19 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 20 | 26.5 micrograms per liter (µg/L) | Standard Deviation 497.52 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 12 | -42.4 micrograms per liter (µg/L) | Standard Deviation 356.19 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Baseline | 919.3 micrograms per liter (µg/L) | Standard Deviation 298.27 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 4 | -23.7 micrograms per liter (µg/L) | Standard Deviation 274.39 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Ferritin Concentration | Week 4 | 41.4 micrograms per liter (µg/L) | Standard Deviation 335 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Ferritin Concentration | Baseline | 910.2 micrograms per liter (µg/L) | Standard Deviation 408.03 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Ferritin Concentration | Week 8 | 29.4 micrograms per liter (µg/L) | Standard Deviation 361.29 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Ferritin Concentration | Week 12 | -68.0 micrograms per liter (µg/L) | Standard Deviation 275.11 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Ferritin Concentration | Week 16 | -144.0 micrograms per liter (µg/L) | Standard Deviation 358.78 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Ferritin Concentration | Week 20 | -199.4 micrograms per liter (µg/L) | Standard Deviation 370.32 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Ferritin Concentration | Baseline | 745.2 micrograms per liter (µg/L) | Standard Deviation 362.98 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Ferritin Concentration | Week 16 | 27.8 micrograms per liter (µg/L) | Standard Deviation 244.67 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Ferritin Concentration | Week 8 | -5.6 micrograms per liter (µg/L) | Standard Deviation 255.1 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Ferritin Concentration | Week 12 | -23.8 micrograms per liter (µg/L) | Standard Deviation 303.39 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Ferritin Concentration | Week 20 | 4.8 micrograms per liter (µg/L) | Standard Deviation 331.76 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Ferritin Concentration | Week 4 | 152.9 micrograms per liter (µg/L) | Standard Deviation 347.97 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Ferritin Concentration | Week 12 | -30.1 micrograms per liter (µg/L) | Standard Deviation 386.24 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Ferritin Concentration | Baseline | 739.5 micrograms per liter (µg/L) | Standard Deviation 329.66 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Ferritin Concentration | Week 16 | -97.2 micrograms per liter (µg/L) | Standard Deviation 188.15 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Ferritin Concentration | Week 20 | -51.6 micrograms per liter (µg/L) | Standard Deviation 253.07 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Ferritin Concentration | Week 8 | -87.8 micrograms per liter (µg/L) | Standard Deviation 285.3 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Ferritin Concentration | Week 4 | 45.5 micrograms per liter (µg/L) | Standard Deviation 320.5 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 8 | -78.3 micrograms per liter (µg/L) | Standard Deviation 254.98 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 4 | -145.6 micrograms per liter (µg/L) | Standard Deviation 211.1 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 20 | -104.8 micrograms per liter (µg/L) | Standard Deviation 347.53 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 12 | -195.3 micrograms per liter (µg/L) | Standard Deviation 304.63 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 16 | -81.8 micrograms per liter (µg/L) | Standard Deviation 447.01 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Baseline | 723.6 micrograms per liter (µg/L) | Standard Deviation 484.29 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Ferritin Concentration | Week 16 | 80.0 micrograms per liter (µg/L) | Standard Deviation 243.24 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Ferritin Concentration | Week 12 | -0.5 micrograms per liter (µg/L) | Standard Deviation 237.99 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Ferritin Concentration | Week 8 | 111.3 micrograms per liter (µg/L) | Standard Deviation 609.61 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Ferritin Concentration | Week 4 | 34.8 micrograms per liter (µg/L) | Standard Deviation 470.43 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Ferritin Concentration | Week 20 | 249.0 micrograms per liter (µg/L) | Standard Deviation 636.33 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Ferritin Concentration | Baseline | 1182.2 micrograms per liter (µg/L) | Standard Deviation 508.67 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 20 | 607.0 micrograms per liter (µg/L) | Standard Deviation 607 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 16 | 62.3 micrograms per liter (µg/L) | Standard Deviation 186.15 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Baseline | 449.6 micrograms per liter (µg/L) | Standard Deviation 423.44 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 12 | -35.0 micrograms per liter (µg/L) | Standard Deviation 157.46 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 8 | 397.8 micrograms per liter (µg/L) | Standard Deviation 453.76 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Ferritin Concentration | Week 4 | -61.5 micrograms per liter (µg/L) | Standard Deviation 17.37 |
Secondary
Mean Change From Baseline in Hepcidin Concentration
Blood samples were collected from participants at defined time points for the assessment of hepcidin concentration. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 12 and Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Participants with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Hepcidin Concentration | Baseline | 194.870 nanograms per milliliter (ng/mL) | Standard Deviation 113.9348 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Hepcidin Concentration | Week 20 | -86.025 nanograms per milliliter (ng/mL) | Standard Deviation 100.4382 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Hepcidin Concentration | Week 12 | -50.565 nanograms per milliliter (ng/mL) | Standard Deviation 57.6474 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Hepcidin Concentration | Week 20 | -38.627 nanograms per milliliter (ng/mL) | Standard Deviation 75.0555 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Hepcidin Concentration | Week 12 | -53.675 nanograms per milliliter (ng/mL) | Standard Deviation 92.1185 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Hepcidin Concentration | Baseline | 208.816 nanograms per milliliter (ng/mL) | Standard Deviation 85.1667 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Hepcidin Concentration | Week 12 | -66.646 nanograms per milliliter (ng/mL) | Standard Deviation 152.3178 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Hepcidin Concentration | Baseline | 259.161 nanograms per milliliter (ng/mL) | Standard Deviation 134.9995 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Hepcidin Concentration | Week 20 | -83.685 nanograms per milliliter (ng/mL) | Standard Deviation 95.7049 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Hepcidin Concentration | Week 20 | -93.412 nanograms per milliliter (ng/mL) | Standard Deviation 115.2839 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Hepcidin Concentration | Baseline | 185.852 nanograms per milliliter (ng/mL) | Standard Deviation 105.6611 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Hepcidin Concentration | Week 12 | -55.283 nanograms per milliliter (ng/mL) | Standard Deviation 77.1648 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Hepcidin Concentration | Week 12 | -34.868 nanograms per milliliter (ng/mL) | Standard Deviation 89.7176 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Hepcidin Concentration | Baseline | 215.608 nanograms per milliliter (ng/mL) | Standard Deviation 130.735 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Hepcidin Concentration | Week 20 | -83.012 nanograms per milliliter (ng/mL) | Standard Deviation 98.7521 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Hepcidin Concentration | Week 12 | -74.797 nanograms per milliliter (ng/mL) | Standard Deviation 126.1667 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Hepcidin Concentration | Baseline | 160.760 nanograms per milliliter (ng/mL) | Standard Deviation 102.6261 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Hepcidin Concentration | Week 20 | -43.701 nanograms per milliliter (ng/mL) | Standard Deviation 80.8411 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Hepcidin Concentration | Week 20 | -80.680 nanograms per milliliter (ng/mL) | Standard Deviation 125.2481 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Hepcidin Concentration | Baseline | 143.519 nanograms per milliliter (ng/mL) | Standard Deviation 124.6749 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Hepcidin Concentration | Week 12 | -62.787 nanograms per milliliter (ng/mL) | Standard Deviation 96.1842 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Hepcidin Concentration | Week 12 | -128.587 nanograms per milliliter (ng/mL) | Standard Deviation 262.63 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Hepcidin Concentration | Week 20 | -152.243 nanograms per milliliter (ng/mL) | Standard Deviation 218.9284 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Hepcidin Concentration | Baseline | 239.958 nanograms per milliliter (ng/mL) | Standard Deviation 151.3859 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Hepcidin Concentration | Week 12 | -1.062 nanograms per milliliter (ng/mL) | Standard Deviation 30.4842 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Hepcidin Concentration | Week 20 | -9.023 nanograms per milliliter (ng/mL) | Standard Deviation 80.4001 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Hepcidin Concentration | Baseline | 74.748 nanograms per milliliter (ng/mL) | Standard Deviation 40.2119 |
Secondary
Mean Change From Baseline in Iron Concentration
Blood samples were collected from participants at defined time points for the assessment of iron indices, including iron concentration. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Participants with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Iron Concentration | Week 8 | -5.5 micrograms per deciliter (µg/dL) | Standard Deviation 45.04 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Iron Concentration | Week 20 | -14.2 micrograms per deciliter (µg/dL) | Standard Deviation 41.11 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Iron Concentration | Week 4 | -8.0 micrograms per deciliter (µg/dL) | Standard Deviation 34.49 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Iron Concentration | Baseline | 87.4 micrograms per deciliter (µg/dL) | Standard Deviation 38.46 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Iron Concentration | Week 16 | -22.8 micrograms per deciliter (µg/dL) | Standard Deviation 39.39 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Iron Concentration | Week 12 | -2.7 micrograms per deciliter (µg/dL) | Standard Deviation 38.24 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Iron Concentration | Week 20 | -9.5 micrograms per deciliter (µg/dL) | Standard Deviation 27.87 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Iron Concentration | Week 16 | -18.3 micrograms per deciliter (µg/dL) | Standard Deviation 39.85 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Iron Concentration | Week 4 | -11.2 micrograms per deciliter (µg/dL) | Standard Deviation 33.59 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Iron Concentration | Week 12 | -22.2 micrograms per deciliter (µg/dL) | Standard Deviation 43.14 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Iron Concentration | Week 8 | -15.0 micrograms per deciliter (µg/dL) | Standard Deviation 40.51 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Iron Concentration | Baseline | 93.9 micrograms per deciliter (µg/dL) | Standard Deviation 36.56 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 8 | -8.6 micrograms per deciliter (µg/dL) | Standard Deviation 44.3 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 16 | -17.9 micrograms per deciliter (µg/dL) | Standard Deviation 53.89 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 20 | -16.6 micrograms per deciliter (µg/dL) | Standard Deviation 46.49 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 12 | -26.0 micrograms per deciliter (µg/dL) | Standard Deviation 33.03 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Baseline | 90.1 micrograms per deciliter (µg/dL) | Standard Deviation 35.09 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 4 | -18.3 micrograms per deciliter (µg/dL) | Standard Deviation 22.83 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Iron Concentration | Week 4 | 3.3 micrograms per deciliter (µg/dL) | Standard Deviation 35.23 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Iron Concentration | Baseline | 57.7 micrograms per deciliter (µg/dL) | Standard Deviation 26.71 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Iron Concentration | Week 8 | 4.5 micrograms per deciliter (µg/dL) | Standard Deviation 24.06 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Iron Concentration | Week 12 | -2.8 micrograms per deciliter (µg/dL) | Standard Deviation 40.49 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Iron Concentration | Week 16 | -0.7 micrograms per deciliter (µg/dL) | Standard Deviation 10.26 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Iron Concentration | Week 20 | 28.7 micrograms per deciliter (µg/dL) | Standard Deviation 67.73 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Iron Concentration | Baseline | 80.9 micrograms per deciliter (µg/dL) | Standard Deviation 36.94 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Iron Concentration | Week 16 | 5.2 micrograms per deciliter (µg/dL) | Standard Deviation 30.27 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Iron Concentration | Week 8 | -5.9 micrograms per deciliter (µg/dL) | Standard Deviation 36.91 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Iron Concentration | Week 12 | -0.4 micrograms per deciliter (µg/dL) | Standard Deviation 40.2 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Iron Concentration | Week 20 | -3.1 micrograms per deciliter (µg/dL) | Standard Deviation 32.43 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Iron Concentration | Week 4 | 9.6 micrograms per deciliter (µg/dL) | Standard Deviation 29.67 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Iron Concentration | Week 12 | -5.1 micrograms per deciliter (µg/dL) | Standard Deviation 27.54 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Iron Concentration | Baseline | 73.1 micrograms per deciliter (µg/dL) | Standard Deviation 22.23 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Iron Concentration | Week 16 | -4.6 micrograms per deciliter (µg/dL) | Standard Deviation 30.31 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Iron Concentration | Week 20 | 13.4 micrograms per deciliter (µg/dL) | Standard Deviation 16.03 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Iron Concentration | Week 8 | 11.7 micrograms per deciliter (µg/dL) | Standard Deviation 40.33 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Iron Concentration | Week 4 | 1.7 micrograms per deciliter (µg/dL) | Standard Deviation 23.37 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 8 | -12.6 micrograms per deciliter (µg/dL) | Standard Deviation 26.55 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 4 | -6.6 micrograms per deciliter (µg/dL) | Standard Deviation 32.86 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 20 | -8.4 micrograms per deciliter (µg/dL) | Standard Deviation 28.94 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 12 | -16.1 micrograms per deciliter (µg/dL) | Standard Deviation 22.88 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 16 | -13.9 micrograms per deciliter (µg/dL) | Standard Deviation 44.05 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Baseline | 65.7 micrograms per deciliter (µg/dL) | Standard Deviation 23.93 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Iron Concentration | Week 16 | 19.5 micrograms per deciliter (µg/dL) | Standard Deviation 53.03 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Iron Concentration | Week 12 | -2.5 micrograms per deciliter (µg/dL) | Standard Deviation 43.94 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Iron Concentration | Week 8 | 0.3 micrograms per deciliter (µg/dL) | Standard Deviation 11.09 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Iron Concentration | Week 4 | 8.6 micrograms per deciliter (µg/dL) | Standard Deviation 17.36 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Iron Concentration | Week 20 | -15.3 micrograms per deciliter (µg/dL) | Standard Deviation 43.19 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Iron Concentration | Baseline | 81.6 micrograms per deciliter (µg/dL) | Standard Deviation 37.01 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 20 | -10.3 micrograms per deciliter (µg/dL) | Standard Deviation 21.57 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 16 | -12.0 micrograms per deciliter (µg/dL) | Standard Deviation 24.06 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Baseline | 58.4 micrograms per deciliter (µg/dL) | Standard Deviation 18.77 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 12 | -12.6 micrograms per deciliter (µg/dL) | Standard Deviation 28.99 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 8 | 2.0 micrograms per deciliter (µg/dL) | Standard Deviation 20.33 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Iron Concentration | Week 4 | 3.8 micrograms per deciliter (µg/dL) | Standard Deviation 25.79 |
Secondary
Mean Change From Baseline in Reticulocyte Count
Blood samples were collected from participants at defined time points for the assessment of reticulocyte count. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 1, Week 4, Week 8, Week 11, Week 12, Week 13, Week 16, and Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Participants with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 13 | 16.7 10^3 cells/microliter (µL) | Standard Deviation 27.07 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Baseline | 51.9 10^3 cells/microliter (µL) | Standard Deviation 27.57 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 12 | 16.1 10^3 cells/microliter (µL) | Standard Deviation 32.6 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 20 | 14.5 10^3 cells/microliter (µL) | Standard Deviation 25.74 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 1 | 3.1 10^3 cells/microliter (µL) | Standard Deviation 24.09 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 16 | 13.9 10^3 cells/microliter (µL) | Standard Deviation 35.4 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 11 | 11.7 10^3 cells/microliter (µL) | Standard Deviation 25.06 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 8 | 14.0 10^3 cells/microliter (µL) | Standard Deviation 31.4 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 4 | 14.6 10^3 cells/microliter (µL) | Standard Deviation 32.25 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 13 | 12.1 10^3 cells/microliter (µL) | Standard Deviation 43.12 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 4 | 14.9 10^3 cells/microliter (µL) | Standard Deviation 29.45 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Baseline | 47.2 10^3 cells/microliter (µL) | Standard Deviation 17.81 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 8 | 23.9 10^3 cells/microliter (µL) | Standard Deviation 39.26 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 11 | 20.2 10^3 cells/microliter (µL) | Standard Deviation 25.8 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 20 | 13.2 10^3 cells/microliter (µL) | Standard Deviation 24.5 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 12 | 16.3 10^3 cells/microliter (µL) | Standard Deviation 34.27 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 1 | 6.9 10^3 cells/microliter (µL) | Standard Deviation 30.6 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 16 | 19.6 10^3 cells/microliter (µL) | Standard Deviation 37.61 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 13 | 16.4 10^3 cells/microliter (µL) | Standard Deviation 26.53 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 11 | 21.0 10^3 cells/microliter (µL) | Standard Deviation 35.12 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 4 | 0.8 10^3 cells/microliter (µL) | Standard Deviation 40.68 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 1 | 1.0 10^3 cells/microliter (µL) | Standard Deviation 22.42 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Baseline | 48.8 10^3 cells/microliter (µL) | Standard Deviation 27.27 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 12 | 22.2 10^3 cells/microliter (µL) | Standard Deviation 26.72 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 8 | 23.1 10^3 cells/microliter (µL) | Standard Deviation 38.98 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 20 | 23.8 10^3 cells/microliter (µL) | Standard Deviation 26.49 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 16 | 8.3 10^3 cells/microliter (µL) | Standard Deviation 34.16 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Baseline | 59.3 10^3 cells/microliter (µL) | Standard Deviation 42.02 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 8 | 9.1 10^3 cells/microliter (µL) | Standard Deviation 46.38 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 20 | 10.3 10^3 cells/microliter (µL) | Standard Deviation 41.33 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 11 | 26.2 10^3 cells/microliter (µL) | Standard Deviation 26.2 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 16 | -2.2 10^3 cells/microliter (µL) | Standard Deviation 57.32 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 13 | 46.3 10^3 cells/microliter (µL) | Standard Deviation 57.25 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 4 | -5.6 10^3 cells/microliter (µL) | Standard Deviation 37.38 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 1 | -18.1 10^3 cells/microliter (µL) | Standard Deviation 24.81 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Reticulocyte Count | Week 12 | 47.7 10^3 cells/microliter (µL) | Standard Deviation 66.66 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Baseline | 48.4 10^3 cells/microliter (µL) | Standard Deviation 33.45 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 20 | 16.4 10^3 cells/microliter (µL) | Standard Deviation 35.54 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 12 | 20.3 10^3 cells/microliter (µL) | Standard Deviation 44.3 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 4 | 2.9 10^3 cells/microliter (µL) | Standard Deviation 39.68 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 11 | 32.5 10^3 cells/microliter (µL) | Standard Deviation 70.42 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 8 | 20.4 10^3 cells/microliter (µL) | Standard Deviation 49.42 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 13 | 15.9 10^3 cells/microliter (µL) | Standard Deviation 43.79 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 16 | 9.7 10^3 cells/microliter (µL) | Standard Deviation 30.17 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Reticulocyte Count | Week 1 | -3.9 10^3 cells/microliter (µL) | Standard Deviation 28.51 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 12 | 26.9 10^3 cells/microliter (µL) | Standard Deviation 52.64 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 1 | -6.6 10^3 cells/microliter (µL) | Standard Deviation 33.8 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 4 | 6.1 10^3 cells/microliter (µL) | Standard Deviation 33.24 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 8 | 23.1 10^3 cells/microliter (µL) | Standard Deviation 20.33 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 11 | 9.2 10^3 cells/microliter (µL) | Standard Deviation 41.3 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 13 | 10.5 10^3 cells/microliter (µL) | Standard Deviation 28.8 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 16 | 0.2 10^3 cells/microliter (µL) | Standard Deviation 22.08 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 20 | 10.9 10^3 cells/microliter (µL) | Standard Deviation 29.81 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Baseline | 51.5 10^3 cells/microliter (µL) | Standard Deviation 25.14 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 11 | 3.9 10^3 cells/microliter (µL) | Standard Deviation 46.15 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 1 | 20.4 10^3 cells/microliter (µL) | Standard Deviation 48.64 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Baseline | 62.6 10^3 cells/microliter (µL) | Standard Deviation 25.88 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 8 | 14.0 10^3 cells/microliter (µL) | Standard Deviation 54.6 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 12 | 4.6 10^3 cells/microliter (µL) | Standard Deviation 39.53 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 20 | 38.5 10^3 cells/microliter (µL) | Standard Deviation 44.11 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 4 | 22.5 10^3 cells/microliter (µL) | Standard Deviation 50.53 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 16 | 26.6 10^3 cells/microliter (µL) | Standard Deviation 55.82 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 13 | 0.1 10^3 cells/microliter (µL) | Standard Deviation 46.05 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 16 | -31.5 10^3 cells/microliter (µL) | Standard Deviation 86.97 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 1 | -35.8 10^3 cells/microliter (µL) | Standard Deviation 45.06 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 13 | 2.0 10^3 cells/microliter (µL) | Standard Deviation 83.44 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 11 | -6.7 10^3 cells/microliter (µL) | Standard Deviation 76.89 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 12 | 3.8 10^3 cells/microliter (µL) | Standard Deviation 52.72 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 8 | -3.3 10^3 cells/microliter (µL) | Standard Deviation 67.56 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Baseline | 77.6 10^3 cells/microliter (µL) | Standard Deviation 51.04 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 20 | -3.3 10^3 cells/microliter (µL) | Standard Deviation 52.58 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Reticulocyte Count | Week 4 | -26.8 10^3 cells/microliter (µL) | Standard Deviation 55.44 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Baseline | 83.0 10^3 cells/microliter (µL) | Standard Deviation 45.34 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 11 | -27.2 10^3 cells/microliter (µL) | Standard Deviation 71.36 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 16 | 4.0 10^3 cells/microliter (µL) | Standard Deviation 16.21 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 8 | -21.8 10^3 cells/microliter (µL) | Standard Deviation 69.36 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 12 | -17.3 10^3 cells/microliter (µL) | Standard Deviation 67.06 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 20 | 40.0 10^3 cells/microliter (µL) | Standard Deviation 7.07 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 4 | 17.5 10^3 cells/microliter (µL) | Standard Deviation 26.21 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 1 | -25.2 10^3 cells/microliter (µL) | Standard Deviation 29.73 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Reticulocyte Count | Week 13 | 16.3 10^3 cells/microliter (µL) | Standard Deviation 11.93 |
Secondary
Mean Change From Baseline in Total Iron Binding Capacity
Blood samples were collected from participants at defined time points for the assessment of iron indices, including Total Iron Binding Capacity. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Participants with non-missing values were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 8 | 30.3 µg/dL | Standard Deviation 28.42 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 20 | 38.0 µg/dL | Standard Deviation 28.15 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 4 | 35.9 µg/dL | Standard Deviation 27.11 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Total Iron Binding Capacity | Baseline | 237.8 µg/dL | Standard Deviation 39.28 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 16 | 35.0 µg/dL | Standard Deviation 43 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 12 | 42.4 µg/dL | Standard Deviation 27.1 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 20 | 44.9 µg/dL | Standard Deviation 30.71 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 16 | 27.8 µg/dL | Standard Deviation 35.16 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 4 | 27.7 µg/dL | Standard Deviation 33.58 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 12 | 37.2 µg/dL | Standard Deviation 43.09 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 8 | 37.0 µg/dL | Standard Deviation 40.99 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Total Iron Binding Capacity | Baseline | 230.7 µg/dL | Standard Deviation 39.09 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 8 | -1.1 µg/dL | Standard Deviation 18.38 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 16 | -3.0 µg/dL | Standard Deviation 25.44 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 20 | -9.5 µg/dL | Standard Deviation 29.29 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 12 | -9.9 µg/dL | Standard Deviation 25.85 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Baseline | 234.8 µg/dL | Standard Deviation 44.76 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 4 | -13.4 µg/dL | Standard Deviation 26.02 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 4 | 27.6 µg/dL | Standard Deviation 28.49 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Total Iron Binding Capacity | Baseline | 210.1 µg/dL | Standard Deviation 33.33 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 8 | 26.3 µg/dL | Standard Deviation 23.98 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 12 | 25.1 µg/dL | Standard Deviation 33.9 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 16 | 55.3 µg/dL | Standard Deviation 28.63 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 20 | 51.7 µg/dL | Standard Deviation 37.5 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Total Iron Binding Capacity | Baseline | 235.7 µg/dL | Standard Deviation 38.8 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 16 | 53.1 µg/dL | Standard Deviation 58.33 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 8 | 49.4 µg/dL | Standard Deviation 27.34 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 12 | 41.0 µg/dL | Standard Deviation 39.05 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 20 | 68.4 µg/dL | Standard Deviation 43.4 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 4 | 41.0 µg/dL | Standard Deviation 26.22 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 12 | 54.5 µg/dL | Standard Deviation 44.05 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Total Iron Binding Capacity | Baseline | 223.6 µg/dL | Standard Deviation 34.31 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 16 | 60.9 µg/dL | Standard Deviation 70.5 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 20 | 67.9 µg/dL | Standard Deviation 58.44 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 8 | 58.8 µg/dL | Standard Deviation 24.54 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 4 | 48.2 µg/dL | Standard Deviation 37.78 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 8 | -7.4 µg/dL | Standard Deviation 19.26 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 4 | -0.5 µg/dL | Standard Deviation 21.44 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 20 | -5.4 µg/dL | Standard Deviation 29.78 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 12 | -3.8 µg/dL | Standard Deviation 25.42 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 16 | -13.7 µg/dL | Standard Deviation 31.46 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Baseline | 218.2 µg/dL | Standard Deviation 33.8 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 16 | 42.5 µg/dL | Standard Deviation 62.93 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 12 | 58.0 µg/dL | Standard Deviation 14.45 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 8 | 56.0 µg/dL | Standard Deviation 58.15 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 4 | 44.2 µg/dL | Standard Deviation 53.58 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Total Iron Binding Capacity | Week 20 | 66.7 µg/dL | Standard Deviation 35.22 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change From Baseline in Total Iron Binding Capacity | Baseline | 211.0 µg/dL | Standard Deviation 42.99 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 20 | -6.0 µg/dL | Standard Deviation 21.79 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 16 | -2.5 µg/dL | Standard Deviation 18.52 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Baseline | 225.6 µg/dL | Standard Deviation 98.15 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 12 | -0.6 µg/dL | Standard Deviation 15.32 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 8 | -24.8 µg/dL | Standard Deviation 58.79 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change From Baseline in Total Iron Binding Capacity | Week 4 | 7.8 µg/dL | Standard Deviation 14.38 |
Secondary
Mean Change in Hb Between Baseline and the SEP
Change from Baseline was calculated as the SEP value minus the Baseline value. The Baseline Hb value was defined as the average of the final two Hb values prior to start of dosing on Day 1. The SEP value was the average Hb value from Week 18 to Week 20.
Time frame: Baseline; Week 18 to Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Participants with non-missing values were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change in Hb Between Baseline and the SEP | -0.197 g/dL | Standard Deviation 1.1597 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change in Hb Between Baseline and the SEP | -0.186 g/dL | Standard Deviation 0.8703 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change in Hb Between Baseline and the SEP | 0.070 g/dL | Standard Deviation 0.9545 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change in Hb Between Baseline and the SEP | 0.114 g/dL | Standard Deviation 1.0242 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change in Hb Between Baseline and the SEP | -0.421 g/dL | Standard Deviation 0.837 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Change in Hb Between Baseline and the SEP | -0.545 g/dL | Standard Deviation 0.9771 |
| High Dose of Epoetin Alfa: Epoetin Alfa | Mean Change in Hb Between Baseline and the SEP | 0.343 g/dL | Standard Deviation 0.8897 |
| ESA Hyporesponder: Vadadustat 600 mg | Mean Change in Hb Between Baseline and the SEP | -0.283 g/dL | Standard Deviation 0.7371 |
| ESA Hyporesponder: Epoetin Alfa | Mean Change in Hb Between Baseline and the SEP | -0.400 g/dL | Standard Deviation 1.0157 |
Secondary
Mean Change in Hb From the PEP to the Secondary Evaluation Period (SEP) in Participants Who Transitioned to Three Times Per Week (TIW) Vadadustat Dosing After Week 12
Change from PEP was calculated as the SEP value minus the PEP value. The PEP value was the average Hb value from Week 10 to Week 12. The SEP value was the average Hb value from Week 18 to Week 20. For the Main Study, analysis is presented per dose level according to the starting dose in TIW regimen, as well as being presented as a combined arm for Vadadustat Total (TIW dosing regimen). For the ESA Hyporesponder Parallel Study, a starting dose classification for TIW dosing regimen was not applicable due to no participants switching from Vadadustat QD to TIW dosing.
Time frame: Week 10 to Week 12; Week 18 to Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Only those who switched from Vadadustat QD to TIW dosing after Week 12 were included in the analysis (17 participants overall in Main Study and 0 participants in ESA Hyporesponder Parallel Study).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change in Hb From the PEP to the Secondary Evaluation Period (SEP) in Participants Who Transitioned to Three Times Per Week (TIW) Vadadustat Dosing After Week 12 | -0.050 g/dL | — |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change in Hb From the PEP to the Secondary Evaluation Period (SEP) in Participants Who Transitioned to Three Times Per Week (TIW) Vadadustat Dosing After Week 12 | -1.021 g/dL | Standard Deviation 1.0961 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Change in Hb From the PEP to the Secondary Evaluation Period (SEP) in Participants Who Transitioned to Three Times Per Week (TIW) Vadadustat Dosing After Week 12 | -0.360 g/dL | Standard Deviation 0.4894 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Change in Hb From the PEP to the Secondary Evaluation Period (SEP) in Participants Who Transitioned to Three Times Per Week (TIW) Vadadustat Dosing After Week 12 | -0.103 g/dL | Standard Deviation 1.9225 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Change in Hb From the PEP to the Secondary Evaluation Period (SEP) in Participants Who Transitioned to Three Times Per Week (TIW) Vadadustat Dosing After Week 12 | -0.422 g/dL | Standard Deviation 1.1708 |
Secondary
Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group
Blood samples were collected from participants at defined time points for the assessment of EPO concentration. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 1 (pre-dose), Week 1 +1 (Day 8; pre-dose), Week 11 (pre-dose), and Week 13 (pre-dose)
Population: Pharmacokinetic (PK) Population: all randomized participants who received study drug and had enough drug concentrations to estimate AUC and Cmax. Analysis of this population was based on the dose amount taken at the date of PK sampling for the Vadadustat group. Participants with concentrations below the limit of quantitation (BLQ) for all the time points were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 1 +1 (Day 8) | 15.6 Milliunits per milliliter | Geometric Coefficient of Variation 76.3 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 1 | 12.1 Milliunits per milliliter | Geometric Coefficient of Variation 94.3 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 11 | 14.2 Milliunits per milliliter | Geometric Coefficient of Variation 55.9 |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Baseline | 7.33 Milliunits per milliliter | Geometric Coefficient of Variation 57.3 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 1 +1 (Day 8) | 18.9 Milliunits per milliliter | Geometric Coefficient of Variation 98.2 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Baseline | 9.53 Milliunits per milliliter | Geometric Coefficient of Variation 54 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 1 | 17.5 Milliunits per milliliter | Geometric Coefficient of Variation 97 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 11 | 14.9 Milliunits per milliliter | Geometric Coefficient of Variation 106.2 |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 13 | 15.7 Milliunits per milliliter | Geometric Coefficient of Variation 107.2 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 1 +1 (Day 8) | 16.1 Milliunits per milliliter | Geometric Coefficient of Variation 76 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 11 | 19.4 Milliunits per milliliter | Geometric Coefficient of Variation 78 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Baseline | 9.93 Milliunits per milliliter | Geometric Coefficient of Variation 83.6 |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 13 | 39.2 Milliunits per milliliter | — |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 1 | 15.3 Milliunits per milliliter | Geometric Coefficient of Variation 72.6 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 1 | 14.1 Milliunits per milliliter | Geometric Coefficient of Variation 86.4 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Baseline | 8.77 Milliunits per milliliter | Geometric Coefficient of Variation 48.2 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 1 +1 (Day 8) | 18.0 Milliunits per milliliter | Geometric Coefficient of Variation 49.8 |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 11 | 20.6 Milliunits per milliliter | Geometric Coefficient of Variation 169.6 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 1 +1 (Day 8) | 17.4 Milliunits per milliliter | Geometric Coefficient of Variation 104.8 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Baseline | 6.98 Milliunits per milliliter | Geometric Coefficient of Variation 61.6 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 1 | 20.2 Milliunits per milliliter | Geometric Coefficient of Variation 90.8 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 11 | 17.3 Milliunits per milliliter | Geometric Coefficient of Variation 53.4 |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 13 | 10.5 Milliunits per milliliter | Geometric Coefficient of Variation 47.1 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 1 | 12.9 Milliunits per milliliter | Geometric Coefficient of Variation 54.2 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Baseline | 8.03 Milliunits per milliliter | Geometric Coefficient of Variation 53.2 |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Mean Serum Concentration of Erythropoietin (EPO) for Vadadustat Treatment Groups by Strata of Epoetin Alfa Dose Group | Week 1 +1 (Day 8) | 9.49 Milliunits per milliliter | Geometric Coefficient of Variation 37.1 |
Secondary
Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of t1/2 of Vadadustat following a single dose.
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Population: PK Population. Analysis of this population was based on the dose amount taken at the date of PK sampling for the Vadadustat group. Participants with non-missing values were included in the analysis. PK parameter of plasma Vadadustat concentration for Vadadustat treatment groups without dose normalization by strata of Epoetin Alfa dose group were included for the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 11 | 6.73 Hours |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 1 | 8.53 Hours |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 8.82 Hours |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 11 | 10.4 Hours |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 1 | 10.5 Hours |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 13 | 11.0 Hours |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 8.83 Hours |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 1 | 12.5 Hours |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 10.1 Hours |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 11 | 6.49 Hours |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 12.4 Hours |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 1 | 10.3 Hours |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 11 | 3.95 Hours |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 14.6 Hours |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 13 | 5.01 Hours |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 11 | 5.65 Hours |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 1 | 11.0 Hours |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 1 | 9.01 Hours |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Median Terminal Half-life (t1/2) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 11.7 Hours |
Secondary
Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose
Blood samples were collected from participants at defined time points for the assessment of Tmax of Vadadustat following a single dose.
Time frame: Day 1; Week 1, Week 1 +1 (Day 8), Week 11, Week 13: pre-dose, 2 hours (h), 3.5h, and 5h post-dose, and additionally at 7h and 10.5h post-dose
Population: PK Population. Analysis of this population was based on the dose amount taken at the date of PK sampling for Vadadustat group. Participants with non-missing values were included in the analysis. PK parameter of plasma Vadadustat concentration for Vadadustat treatment groups without dose normalization by strata of Epoetin Alfa dose group were included for the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 11 | 3.23 Hours |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 3.28 Hours |
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 1 | 2.08 Hours |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 11 | 3.50 Hours |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 13 | 1.98 Hours |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 1 | 2.72 Hours |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 2.11 Hours |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 1 | 3.48 Hours |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 3.33 Hours |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 11 | 3.50 Hours |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 13 | 4.25 Hours |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 1 | 3.50 Hours |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 3.30 Hours |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 11 | 2.03 Hours |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 13 | 2.04 Hours |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 1 | 2.00 Hours |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 2.17 Hours |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 11 | 2.11 Hours |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 1 +1 (Day 8) | 3.42 Hours |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Median Time to Reach Cmax (Tmax) of Vadadustat Following a Single Dose | Week 1 | 3.28 Hours |
Secondary
Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation
Iron supplementation was performed to maintain ferritin ≥200 nanograms/milliliters (ng/mL) and transferrin saturation (TSAT) ≥20%.
Time frame: Up to Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation | 23 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation | 21 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation | 16 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation | 10 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation | 14 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation | 18 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation | 10 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation | 4 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants Requiring at Least One Intravenous (IV) Elemental Iron Supplementation | 5 Participants |
Secondary
Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue
ESA rescue therapy was administered in participants with Hb ≥8.5 g/dL, and was stopped when Hb reached ≥9.0 g/dL.
Time frame: Up to Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue | 2 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue | 8 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue | 3 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue | 5 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue | 5 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue | 3 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue | 1 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue | 3 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants Requiring Erythropoiesis-stimulating Agent (ESA) Rescue | 1 Participants |
Secondary
Number of Participants Requiring Red Blood Cell (RBC) Transfusion
RBC transfusion was administered as rescue therapy in the event of an acute or severe loss of blood.
Time frame: Up to Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Participants with non-missing values were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Requiring Red Blood Cell (RBC) Transfusion | 0 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Requiring Red Blood Cell (RBC) Transfusion | 1 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Requiring Red Blood Cell (RBC) Transfusion | 0 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants Requiring Red Blood Cell (RBC) Transfusion | 3 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants Requiring Red Blood Cell (RBC) Transfusion | 1 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants Requiring Red Blood Cell (RBC) Transfusion | 2 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants Requiring Red Blood Cell (RBC) Transfusion | 0 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants Requiring Red Blood Cell (RBC) Transfusion | 1 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants Requiring Red Blood Cell (RBC) Transfusion | 1 Participants |
Secondary
Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP
The target range for Hb was from 10.0 to 11.0 g/dL. The PEP was comprised of Week 10 to Week 12.
Time frame: Week 10 to Week 12
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Participants with non-missing values were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP | 14 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP | 19 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP | 18 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP | 1 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP | 6 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP | 6 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP | 8 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP | 0 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants With a Mean Increase in Hb From Baseline to the PEP ≥0.5 g/dL or With Hb Values Within the Target Range at the PEP | 1 Participants |
Secondary
Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP
The target range for Hb was from 10.0 to 11.0 grams per g/dL. The SEP was comprised of Week 18 to Week 20.
Time frame: Week 18 to Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Participants with non-missing values were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP | 10 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP | 11 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP | 14 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP | 3 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP | 5 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP | 2 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP | 8 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP | 1 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants With a Mean Increase in Hb From Baseline to the SEP ≥0.5 g/dL or With Hb Values Within the Target Range at the SEP | 2 Participants |
Secondary
Number of Participants With Hb Values Within the Target Range at the PEP
The target range for Hb was from 10.0 to 11.0 g/dL, inclusive. The PEP was comprised of Week 10 to Week 12.
Time frame: Week 10 to Week 12
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Participants with non-missing values were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With Hb Values Within the Target Range at the PEP | 12 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With Hb Values Within the Target Range at the PEP | 13 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With Hb Values Within the Target Range at the PEP | 15 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With Hb Values Within the Target Range at the PEP | 1 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With Hb Values Within the Target Range at the PEP | 4 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants With Hb Values Within the Target Range at the PEP | 4 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With Hb Values Within the Target Range at the PEP | 6 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants With Hb Values Within the Target Range at the PEP | 0 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants With Hb Values Within the Target Range at the PEP | 0 Participants |
Secondary
Number of Participants With Hb Values Within the Target Range at the SEP
The target range for Hb was from 10.0 to 11.0 g/dL. The SEP was comprised of Week 18 to Week 20.
Time frame: Week 18 to Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Participants with non-missing values were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With Hb Values Within the Target Range at the SEP | 6 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With Hb Values Within the Target Range at the SEP | 7 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With Hb Values Within the Target Range at the SEP | 9 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With Hb Values Within the Target Range at the SEP | 2 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With Hb Values Within the Target Range at the SEP | 3 Participants |
| High Dose of Epoetin Alfa: Vadadustat 600 mg | Number of Participants With Hb Values Within the Target Range at the SEP | 2 Participants |
| High Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With Hb Values Within the Target Range at the SEP | 6 Participants |
| ESA Hyporesponder: Vadadustat 600 mg | Number of Participants With Hb Values Within the Target Range at the SEP | 1 Participants |
| ESA Hyporesponder: Epoetin Alfa | Number of Participants With Hb Values Within the Target Range at the SEP | 1 Participants |
Secondary
Number of Participants With Hb Values Within the Target Range at the SEP in Participants Who Transitioned to TIW Vadadustat Dosing
The target range for Hb was from 10.0 to 11.0 g/dL. The SEP was comprised of Week 18 to Week 20. For the Main Study, analysis is presented per dose level according to the starting dose in TIW regimen, as well as being presented as a combined arm for Vadadustat Total (TIW dosing regimen). For the ESA Hyporesponder Parallel Study, a starting dose classification for TIW dosing regimen was not applicable due to no participants switching from Vadadustat QD to TIW dosing.
Time frame: Week 18 to Week 20
Population: Randomized Population. Analysis of this population was based on the randomized treatment. Only those who switched from Vadadustat QD to TIW dosing after Week 12 were included in the analysis (17 participants overall in Main Study and 0 participants in ESA Hyporesponder Parallel Study).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With Hb Values Within the Target Range at the SEP in Participants Who Transitioned to TIW Vadadustat Dosing | 0 Participants |
| Low Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With Hb Values Within the Target Range at the SEP in Participants Who Transitioned to TIW Vadadustat Dosing | 2 Participants |
| Low Dose of Epoetin Alfa: Epoetin Alfa | Number of Participants With Hb Values Within the Target Range at the SEP in Participants Who Transitioned to TIW Vadadustat Dosing | 2 Participants |
| High Dose of Epoetin Alfa: Vadadustat 300 mg | Number of Participants With Hb Values Within the Target Range at the SEP in Participants Who Transitioned to TIW Vadadustat Dosing | 3 Participants |
| High Dose of Epoetin Alfa: Vadadustat 450 mg | Number of Participants With Hb Values Within the Target Range at the SEP in Participants Who Transitioned to TIW Vadadustat Dosing | 7 Participants |