| Outcome Measures: |
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., Baseline; Week 10 to Week 12|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., Up to Week 24|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., Up to Week 24|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., Up to Week 24|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., Weeks 13 - 20 | 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., Week 10 to Week 12|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., Week 10 to Week 12; Week 18 to Week 20|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., Baseline; Week 18 to Week 20|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., 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, 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., Week 18 to Week 20|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., 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, 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., Week 18 to Week 20|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%., Up to Week 20|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., Up to Week 20|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., Up to Week 20|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., Baseline; Week 1 (pre-dose), Week 1 +1 (Day 8; pre-dose), Week 11 (pre-dose), and Week 13 (pre-dose)|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., Baseline; Week 1, Week 4, Week 8, Week 11, Week 12, Week 13, Week 16, and Week 20|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., Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20|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., Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20|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., Baseline; Week 4, Week 8, Week 12, Week 16, and Week 20|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., Baseline; Week 12 and Week 20|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., 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|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., 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|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., 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|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., 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|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., 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|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., 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|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., 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
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| Locations: |
Research Site, Fresno, California, 93720, United States|Research Site, Granada Hills, California, 91344, United States|Research Site, Los Angeles, California, 90022, United States|Research Site, Northridge, California, 91324, United States|Research Site, Riverside, California, 92501, United States|Research Site #1, San Dimas, California, 91773, United States|Research Site #2, San Dimas, California, 91773, United States|Research Site, San Gabriel, California, 91776, United States|Research Site, Tarzana, California, 91356, United States|Research Site, Vacaville, California, 95688, United States|Research Site, Victorville, California, 92394, United States|Research Site, Denver, Colorado, 80230, United States|Research Site, Bridgeport, Connecticut, 06606, United States|Research Site, Hartford, Connecticut, 06762, United States|Research Site, Coral Gables, Florida, 33134, United States|Research Site, Hollywood, Florida, 33024, United States|Research Site, Miami, Florida, 33126, United States|Research Site, Miami, Florida, 33134, United States|Research Site, Miami, Florida, 33150, United States|Research Site, Tampa, Florida, 33607, United States|Research Site, Tampa, Florida, 33614, United States|Research Site, Winter Park, Florida, 32789, United States|Research Site, Augusta, Georgia, 30909, United States|Research Site, Statesboro, Georgia, 30458, United States|Research Site, Roseville, Michigan, 48066, United States|Research Site #1, Minneapolis, Minnesota, 55404, United States|Research Site #2, Minneapolis, Minnesota, 55404, United States|Research Site, Kansas City, Missouri, 64111, United States|Research Site, Las Vegas, Nevada, 89107, United States|Research Site, Bronx, New York, 10461, United States|Research Site, Asheville, North Carolina, 28801, United States|Research Site, Wilmington, North Carolina, 28401, United States|Research Site, Canton, Ohio, 44718, United States|Research Site, Oklahoma City, Oklahoma, 73116, United States|Research Site, El Paso, Texas, 79915, United States|Research Site, Houston, Texas, 77004, United States|Research Site, San Antonio, Texas, 78229, United States|Research Site, San Antonio, Texas, 78258, United States|Research Site, Chesapeake, Virginia, 23320, United States|Research Site, Norfolk, Virginia, 23510, United States|Research Site, Wauwatosa, Wisconsin, 53226, United States
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