Anemia, End Stage Renal Disease
Conditions
Keywords
Kidney, End Stage Renal Disease, ESRD, Chronic Kidney Disease, CKD, Renal, Anemia, Oral anemia treatment, Hemoglobin levels, Blood count, Erythropoietin, Hemodialysis, Normoresponder, Hyporesponder
Brief summary
The primary objective of this study is to evaluate the efficacy and safety of roxadustat in participants with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) therapy, previously treated with intravenous (IV) epoetin alfa.
Detailed description
Dose ranging study with consecutive cohorts in two participant populations: participants normally responding to current anemia treatment (epoetin alfa) (normoresponders: participants with baseline epoetin alfa dose at study entry 75 to 450 international units \[IU\]/kilograms \[kg\]/week) and participants not responding well to current treatment (hyporesponders: participants with maintenance epoetin alfa dose above 450 IU/kg/week). Normoresponders are randomized to study drug roxadustat or epoetin alfa at a ratio of 3:1; hyporesponders are randomized to study drug roxadustat or epoetin alfa or placebo at a ratio of 2:1:1. The study objectives are to demonstrate that roxadustat is effective in maintaining hemoglobin (Hb) levels when converting from epoetin alfa and to establish optimum starting doses and dose adjustment regimens for Hb maintenance.
Interventions
DRUGRoxadustat
Roxadustat will be administered per dose and schedule specified in the arms.
DRUGEpoetin Alfa
Epoetin Alfa will be administered per dose and schedule specified in the arms.
OTHERPlacebo
Placebo matching to roxadustat will be administered per schedule specified in the arm.
Sponsors
AstraZeneca
Astellas Pharma Inc
FibroGen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * ESRD and receiving maintenance HD TIW for ≥4 months prior to Day 1 * Two most recent Hb values obtained during screening period must be within the ranges set below: i) Group A. Normoresponder Criteria: Hb range in the 8 weeks prior to randomization within 9.0 to 13.5 g/dL ii) Group B. Hyporesponder Criteria: Hb range in the 8 weeks prior to randomization within 8.5 to 13.5 g/dL * Epoetin alfa, dose requirements: i) Group A. Normoresponder Criteria - Cohorts A-1 to A-12: Stable IV epoetin alfa dose at baseline (that is, no more than a 30% fluctuation in the weekly dose) during the 4 weeks prior to study Day -3 1. Cohorts A-1 to A-4: Current and previous (past 4 weeks) epoetin alfa dose range 25 to 85 IU/kg/dose, TIW; weekly dose between 75 and 255 IU/kg/week 2. Cohort A-5: Current and previous (past 4 weeks) epoetin alfa dose range ≥85 to 115 IU/kg/dose, TIW; total weekly dose between 255 and 450 IU/kg/week 3. Cohort A-9: Current and previous (past 4 weeks) epoetin alfa dose range ≥85 to 150 IU/kg/dose, TIW; total weekly dose between 255 and 450 IU/kg/week 4. Cohorts A-6 to A-8: Current and previous (past 4 weeks) epoetin alfa dose range 25 to 115 IU/kg/dose, TIW, and two times a week (BIW); total weekly dose between 75 and 345 IU/kg/week 5. Cohorts A-10 to A-12: Optional cohorts to be decided (TBD), dosing frequency and dose range to be determined by sponsor ii) Group B. Hyporesponder Criteria: <!-- --> 1. Cohort B-1 (completed): Current and previous (past 4 weeks) epoetin alfa dose range 125 to 400 IU/kg/dose, TIW; weekly dose between 375 and 1200 IU/kg/week 2. Cohort B-2 to B-4: Current and previous (past 4 weeks) epoetin alfa dose range \>115 IU/kg/dose, TIW; total weekly dose \>345 IU/kg/week no requirement for stability of epoetin alfa doses * Complete Blood Count (CBC), Hematology, liver function blood tests, serum folate and vitamin B12 within acceptable limits * Absence of active or chronic gastrointestinal bleeding * High sensitivity C-reactive protein (hsCRP) \<60 mg/liter for normoresponders Cohorts A-8 through A-12 enrolled under Amendment 3; no hsCRP criteria for hyporesponders * Body weight: 40 to 140 kg (dry weight) * Body mass index (BMI): 18 to 45 kg/meter square (m\^2) * Dialysis vascular access via native arteriovenous fistula or synthetic graft, or permanent (tunneled) catheter (not via temporary catheter); permanent and temporary catheters, however, are still prohibited in Cohort A-5 Key
Exclusion criteria
* Anticipated change in HD prescription * Any clinically significant infection or evidence of an underlying infection * Positive for any of the following: Human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab) * History of chronic liver disease * New York Heart Association Class III or IV congestive heart failure * Chronic inflammatory disease that could impact erythropoiesis (for example, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission * History of myelodysplastic syndrome * History of hemosiderosis, hemochromatosis, polycystic kidney disease, or anephric * Active hemolysis or diagnosis of hemolytic syndrome * Known bone marrow fibrosis * Uncontrolled or symptomatic secondary hyperparathyroidism * Any prior organ transplantation * Drug-treated gastroparesis or short-bowel syndrome * History of alcohol or drug abuse; or a positive drug screen for a substance that has not been prescribed for the participant * Prior treatment with roxadustat * Diagnosis or suspicion of renal cell carcinoma * Red blood cell (RBC) transfusion within 12 weeks prior to Day 1, or anticipated need for RBC transfusion during the dosing period * IV iron supplement within 2 weeks prior to Day 1 and/or unwilling to withhold IV iron during the dosing/treatment period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only | Week 7 | Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. Last observation carried forward (LOCF) method was used to impute missing values. |
| Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks | Week 7 | Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. |
| Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks | Weeks 17, 18, 19, and 20 | The average of the mean Hb values that were above 11 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Baseline up to Week 6 | Number of participants who required dose increase, dose reduce, dose interruption or dose resume were reported. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants. |
| Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | Weeks 17, 18, 19, and 20 | The average of the mean Hb values that were within 11-13 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values. |
| Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | Baseline up to Week 6 | Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron. |
| Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Baseline up to Week 19 | Number of participants who required dose increase, dose reduce, dose interruption or dose resume were reported. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants. |
| Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | Week 7 | — |
| Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks | Week 7 | — |
| Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | Weeks 17, 18, 19, and 20 | The average of the mean Hb values that were within 10-13 g/dL at Weeks 17, 18, 19, and 20 are presented. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants. LOCF method was used to impute missing values. |
| Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Weeks 8, 10, 12, 14, 17, 19, and 20 | Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants. |
| Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks | Baseline up to Week 19 | Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron. |
| Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | Baseline up to Week 6 | — |
| Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks | Baseline up to Week 19 | — |
| Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6 | Baseline up to Week 6 | The rate of rise was computed as the slope of the regression line of change in Hb level (in g/dL) vs. time (in weeks) using Random Coefficient Model. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants. |
| Trough Plasma Concentration of Roxadustat and Epoetin Alfa | Predose, 4, 8, 12, 24, 48, and 72 hours postdose at Weeks 1 and 6 | — |
| Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level | Week 7 | Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants. |
| Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | Baseline, Week 7 | Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. |
| Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Baseline, Weeks 8, 10, 12, 14, 17, 19, and 20 | Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. |
Countries
United States
Participant flow
Pre-assignment details
Normoresponder participants were enrolled sequentially in 10 cohorts (A-1 to A-10) with the exception of Cohort A-5 in parallel enrollment with A-6 to A-8. Hyporesponder participants were enrolled in 2 cohorts (B-1 and B-2). Normoresponder participants were those with stable baseline epoetin alfa doses between 75 and 450 international units (IU)/kilogram (kg)/week, while hyporeponders required maintenance epoetin alfa dose above 450 IU/kg/week.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 mg/kg, administered orally TIW in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb. | 12 |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb. | 12 |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb. | 12 |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb. | 12 |
| Cohort A-5 (Roxadustat 1.8 mg/kg TIW) Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb. | 12 |
| Cohort A-6 (Roxadustat 1.3 mg/kg TIW) Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb. | 12 |
| Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg) Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (\>60 to 90 kg), and heavy weight (\>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb. | 12 |
| Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg) Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (\>60 to 90 kg), and heavy weight (\>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb. | 12 |
| Cohort A-9 (Roxadustat 2.0 mg/kg) Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb. | 2 |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (\>60 to 90 kg), and heavy weight (\>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb. | 10 |
| Cohorts A (Epoetin Alfa) Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants. | 36 |
| Cohort B-1 (Roxadustat 1.5 mg/kg TIW) Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb. | 4 |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) Hyporesponsive participants (with baseline epoetin alfa dosage \>115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb. | 5 |
| Cohort B (Epoetin Alfa) Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants. | 4 |
| Cohort B (Placebo) Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 19 weeks. | 4 |
| Total | 161 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dosing Period 1: 6-Week Treatment | Adverse Event | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Dosing Period 1: 6-Week Treatment | Death | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Dosing Period 1: 6-Week Treatment | Lack of Efficacy | 0 | 1 | 0 | 0 | 3 | 1 | 2 | 2 | 0 | 1 | 0 | 0 | 1 | 0 | 3 |
| Dosing Period 1: 6-Week Treatment | Non-compliance with study drug | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 |
| Dosing Period 1: 6-Week Treatment | Other than specified | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Dosing Period 1: 6-Week Treatment | Protocol Violation | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Dosing Period 1: 6-Week Treatment | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 |
| Dosing Period 2: 19-Week Treatment | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Dosing Period 2: 19-Week Treatment | Death | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Dosing Period 2: 19-Week Treatment | Lack of Efficacy | 0 | 0 | 0 | 0 | 3 | 1 | 2 | 2 | 0 | 1 | 0 | 0 | 1 | 0 | 2 |
| Dosing Period 2: 19-Week Treatment | Non-compliance with study drug | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Dosing Period 2: 19-Week Treatment | Other than specified | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Dosing Period 2: 19-Week Treatment | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dosing Period 2: 19-Week Treatment | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Cohort A-5 (Roxadustat 1.8 mg/kg TIW) | Cohort A-6 (Roxadustat 1.3 mg/kg TIW) | Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg) | Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg) | Cohort A-9 (Roxadustat 2.0 mg/kg) | Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Cohorts A (Epoetin Alfa) | Cohort B-1 (Roxadustat 1.5 mg/kg TIW) | Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Cohort B (Epoetin Alfa) | Cohort B (Placebo) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 3.680644 | 55.1 years STANDARD_DEVIATION 12.1 | 58.8 years STANDARD_DEVIATION 13.6 | 56.6 years STANDARD_DEVIATION 10.8 | 50.8 years STANDARD_DEVIATION 19.4 | 55.2 years STANDARD_DEVIATION 10.6 | 58.7 years STANDARD_DEVIATION 10.1 | 61.9 years STANDARD_DEVIATION 11.9 | 55.7 years STANDARD_DEVIATION 14.5 | 57.0 years STANDARD_DEVIATION 17 | 55.8 years STANDARD_DEVIATION 6.8 | 57.9 years STANDARD_DEVIATION 11 | 55.0 years STANDARD_DEVIATION 8.8 | 60.2 years STANDARD_DEVIATION 5.9 | 47.0 years STANDARD_DEVIATION 12.5 | 58.8 years STANDARD_DEVIATION 8.6 |
| Sex: Female, Male Female | 61 Participants | 4 Participants | 1 Participants | 7 Participants | 5 Participants | 4 Participants | 2 Participants | 5 Participants | 4 Participants | 1 Participants | 3 Participants | 13 Participants | 3 Participants | 5 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 100 Participants | 8 Participants | 11 Participants | 5 Participants | 7 Participants | 8 Participants | 10 Participants | 7 Participants | 8 Participants | 1 Participants | 7 Participants | 23 Participants | 1 Participants | 0 Participants | 2 Participants | 2 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 | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 12 | 1 / 12 | 1 / 12 | 4 / 12 | 2 / 12 | 2 / 12 | 1 / 12 | 2 / 12 | 0 / 2 | 3 / 10 | 2 / 36 | 3 / 4 | 2 / 5 | 0 / 4 | 1 / 4 |
| serious Total, serious adverse events | 0 / 12 | 3 / 12 | 0 / 12 | 4 / 12 | 5 / 12 | 3 / 12 | 5 / 12 | 3 / 12 | 0 / 2 | 3 / 10 | 6 / 36 | 2 / 4 | 2 / 5 | 1 / 4 | 0 / 4 |
Outcome results
Primary
Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks
The average of the mean Hb values that were above 11 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.
Time frame: Weeks 17, 18, 19, and 20
Population: EE population for 19 weeks treatment included all participants randomized designated to receive 19 weeks of study medication and had received study treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion), or who permanently discontinued study medication during the dosing period due to lack of efficacy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks | 4 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks | 4 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks | 6 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks | 5 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks | 6 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks | 2 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks | 4 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks | 8 Participants |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks | 0 Participants |
| Cohort B (Epoetin Alfa) | Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks | 0 Participants |
| Cohort B (Placebo) | Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks | 0 Participants |
Primary
Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks
Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.
Time frame: Week 7
Population: EE population included participants who received treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion) or who permanently discontinued study drug during dosing period due to lack of efficacy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks | 0 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks | 1 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks | 2 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks | 0 Participants |
p-value: 1Fisher Exact
Primary
Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only
Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. Last observation carried forward (LOCF) method was used to impute missing values.
Time frame: Week 7
Population: EE population included participants who received treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (erythropoiesis-stimulating agent \[ESA\], IV Iron or red blood cell \[RBC\] transfusion) or who permanently discontinued study drug during dosing period due to lack of efficacy. Here, 'Overall number of participants analyzed' signifies normoresponder participants who were treated for 6 weeks only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only | 4 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only | 8 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only | 7 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only | 4 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only | 3 Participants |
p-value: 1Fisher Exact
p-value: 0.0698Fisher Exact
p-value: 0.1534Fisher Exact
p-value: 0.2657Fisher Exact
Secondary
Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks
Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.
Time frame: Baseline, Week 7
Population: EE population included participants who received treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion) or who permanently discontinued study drug during dosing period due to lack of efficacy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | -0.40 g/dL | Standard Deviation 1.56 |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | 0.91 g/dL | Standard Deviation 1.59 |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | 0.71 g/dL | Standard Deviation 1.61 |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | 0.25 g/dL | Standard Deviation 1.86 |
| Cohort A (Epoetin Alfa) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | -0.15 g/dL | Standard Deviation 1.36 |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | -0.18 g/dL | Standard Deviation 1.55 |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | -0.32 g/dL | Standard Deviation 1.39 |
| Cohorts A (Epoetin Alfa) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | -0.47 g/dL | Standard Deviation 0.94 |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | -0.00 g/dL | Standard Deviation 2.12 |
| Cohort B (Epoetin Alfa) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | 0.24 g/dL | Standard Deviation 1.82 |
| Cohort B (Placebo) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | -0.51 g/dL | Standard Deviation 1.31 |
| Cohort B-1 (Roxadustat 1.5 mg/kg TIW) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | -2.63 g/dL | — |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | -0.89 g/dL | Standard Deviation 0.74 |
| Cohort B (Epoetin Alfa) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | -0.28 g/dL | Standard Deviation 0.81 |
| Cohort B (Placebo) | Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks | -2.50 g/dL | Standard Deviation 0.23 |
Secondary
Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks
Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.
Time frame: Baseline, Weeks 8, 10, 12, 14, 17, 19, and 20
Population: EE population for 19 weeks treatment included all participants randomized designated to receive 19 weeks of study medication and had received study treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion), or who permanently discontinued study medication during the dosing period due to lack of efficacy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 12 | 0.26 g/dL | Standard Deviation 1.49 |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 19 | -0.11 g/dL | Standard Deviation 1.18 |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 8 | 0.49 g/dL | Standard Deviation 1.31 |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 17 | -0.09 g/dL | Standard Deviation 0.88 |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 20 | -0.39 g/dL | Standard Deviation 1.16 |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 10 | 0.56 g/dL | Standard Deviation 1.49 |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 14 | 0.53 g/dL | Standard Deviation 1.55 |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 12 | 0.04 g/dL | Standard Deviation 1.57 |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 14 | -0.03 g/dL | Standard Deviation 1.73 |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 20 | -0.55 g/dL | Standard Deviation 1.88 |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 19 | -0.32 g/dL | Standard Deviation 1.84 |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 10 | 0.17 g/dL | Standard Deviation 1.65 |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 8 | 0.08 g/dL | Standard Deviation 1.56 |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 17 | -0.09 g/dL | Standard Deviation 1.96 |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 14 | -0.27 g/dL | Standard Deviation 1.29 |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 20 | -0.55 g/dL | Standard Deviation 1.24 |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 10 | -0.17 g/dL | Standard Deviation 1.32 |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 8 | 0.01 g/dL | Standard Deviation 1.51 |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 19 | -0.28 g/dL | Standard Deviation 1.07 |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 12 | -0.10 g/dL | Standard Deviation 1.42 |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 17 | -0.27 g/dL | Standard Deviation 1.07 |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 10 | -0.56 g/dL | Standard Deviation 1.35 |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 17 | -0.48 g/dL | Standard Deviation 1.42 |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 14 | -0.41 g/dL | Standard Deviation 1.44 |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 12 | -0.56 g/dL | Standard Deviation 1.44 |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 19 | -0.82 g/dL | Standard Deviation 1.19 |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 20 | -0.82 g/dL | Standard Deviation 1.27 |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 8 | -0.49 g/dL | Standard Deviation 1.49 |
| Cohort A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 19 | -0.35 g/dL | Standard Deviation 1.2 |
| Cohort A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 14 | -0.24 g/dL | Standard Deviation 1.68 |
| Cohort A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 12 | -0.35 g/dL | Standard Deviation 1.17 |
| Cohort A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 17 | -0.27 g/dL | Standard Deviation 1.18 |
| Cohort A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 20 | -0.33 g/dL | Standard Deviation 1.34 |
| Cohort A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 8 | -0.29 g/dL | Standard Deviation 1.09 |
| Cohort A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 10 | -0.27 g/dL | Standard Deviation 1.22 |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 14 | -0.15 g/dL | Standard Deviation 1.77 |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 8 | 0.05 g/dL | Standard Deviation 2.05 |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 10 | -0.15 g/dL | Standard Deviation 0.07 |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 12 | -0.15 g/dL | Standard Deviation 0.92 |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 17 | -0.30 g/dL | Standard Deviation 0.85 |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 19 | 0.05 g/dL | Standard Deviation 0.07 |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 20 | 0.15 g/dL | Standard Deviation 0.07 |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 14 | 0.33 g/dL | Standard Deviation 2.37 |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 17 | 0.02 g/dL | Standard Deviation 2.06 |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 19 | -0.10 g/dL | Standard Deviation 2.03 |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 10 | 0.26 g/dL | Standard Deviation 2.07 |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 20 | -0.57 g/dL | Standard Deviation 1.68 |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 8 | 0.20 g/dL | Standard Deviation 1.85 |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 12 | 0.38 g/dL | Standard Deviation 2.28 |
| Cohorts A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 8 | -0.21 g/dL | Standard Deviation 1.02 |
| Cohorts A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 14 | -0.50 g/dL | Standard Deviation 1.23 |
| Cohorts A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 10 | -0.34 g/dL | Standard Deviation 1.19 |
| Cohorts A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 12 | -0.48 g/dL | Standard Deviation 1.2 |
| Cohorts A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 17 | -0.45 g/dL | Standard Deviation 1.57 |
| Cohorts A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 20 | -0.36 g/dL | Standard Deviation 1.5 |
| Cohorts A (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 19 | -0.30 g/dL | Standard Deviation 1.43 |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 14 | -2.29 g/dL | Standard Deviation 1.71 |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 12 | -2.02 g/dL | Standard Deviation 1.47 |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 20 | -2.82 g/dL | Standard Deviation 1.19 |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 17 | -2.69 g/dL | Standard Deviation 1.61 |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 10 | -1.46 g/dL | Standard Deviation 1.41 |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 19 | -3.02 g/dL | Standard Deviation 1.08 |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 8 | -0.89 g/dL | Standard Deviation 0.99 |
| Cohort B (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 8 | -0.41 g/dL | Standard Deviation 1.52 |
| Cohort B (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 14 | 0.42 g/dL | Standard Deviation 1.83 |
| Cohort B (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 17 | 0.16 g/dL | Standard Deviation 2.27 |
| Cohort B (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 12 | -0.08 g/dL | Standard Deviation 2.5 |
| Cohort B (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 19 | 0.12 g/dL | Standard Deviation 2.27 |
| Cohort B (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 20 | 0.12 g/dL | Standard Deviation 2.14 |
| Cohort B (Epoetin Alfa) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 10 | 0.19 g/dL | Standard Deviation 1.48 |
| Cohort B (Placebo) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 17 | -2.37 g/dL | Standard Deviation 0 |
| Cohort B (Placebo) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 19 | -2.37 g/dL | Standard Deviation 0 |
| Cohort B (Placebo) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 8 | -2.37 g/dL | Standard Deviation 0 |
| Cohort B (Placebo) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 10 | -2.37 g/dL | Standard Deviation 0 |
| Cohort B (Placebo) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 14 | -2.37 g/dL | Standard Deviation 0 |
| Cohort B (Placebo) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 20 | -2.47 g/dL | Standard Deviation 0.14 |
| Cohort B (Placebo) | Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks | Change at Week 12 | -2.37 g/dL | Standard Deviation 0 |
Secondary
Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks
Time frame: Baseline up to Week 19
Population: Safety population included all participants who were randomized and received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks | 0 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks | 0 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks | 2 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks | 1 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks | 2 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks | 1 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks | 4 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks | 6 Participants |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks | 0 Participants |
| Cohort B (Epoetin Alfa) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks | 1 Participants |
| Cohort B (Placebo) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks | 0 Participants |
Secondary
Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks
Time frame: Baseline up to Week 6
Population: Safety population included all participants who were randomized and received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 0 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 0 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 0 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 1 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 0 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 2 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 1 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 2 Participants |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 1 Participants |
| Cohort B (Epoetin Alfa) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 4 Participants |
| Cohort B (Placebo) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 6 Participants |
| Cohort B-1 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 0 Participants |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 0 Participants |
| Cohort B (Epoetin Alfa) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 1 Participants |
| Cohort B (Placebo) | Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks | 0 Participants |
Secondary
Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level
Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.
Time frame: Week 7
Population: EE population included participants who received treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion) or who permanently discontinued study drug during dosing period due to lack of efficacy. Here, 'Overall number of participants analyzed' signifies participants who were treated for 6 weeks only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level | 3 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level | 7 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level | 6 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level | 3 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level | 2 Participants |
Secondary
Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level
Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.
Time frame: Weeks 8, 10, 12, 14, 17, 19, and 20
Population: EE population for 19 weeks treatment included all participants randomized designated to receive 19 weeks of study medication and had received study treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion), or who permanently discontinued study medication during the dosing period due to lack of efficacy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 17 | 2 Participants |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 19 | 2 Participants |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 12 | 3 Participants |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 8 | 3 Participants |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 10 | 3 Participants |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 14 | 3 Participants |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 20 | 3 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 20 | 3 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 17 | 5 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 10 | 6 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 12 | 6 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 14 | 6 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 8 | 6 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 19 | 4 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 17 | 5 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 20 | 5 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 14 | 6 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 10 | 4 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 8 | 4 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 19 | 5 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 12 | 6 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 14 | 4 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 20 | 2 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 10 | 4 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 19 | 2 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 12 | 4 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 8 | 4 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 17 | 4 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 14 | 1 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 8 | 4 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 10 | 5 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 12 | 3 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 17 | 4 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 19 | 4 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 20 | 5 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 14 | 1 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 20 | 2 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 17 | 1 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 12 | 1 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 19 | 1 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 10 | 0 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 8 | 1 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 10 | 6 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 8 | 6 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 19 | 6 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 17 | 6 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 20 | 5 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 12 | 5 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 14 | 6 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 20 | 7 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 14 | 6 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 19 | 8 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 8 | 9 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 12 | 9 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 17 | 6 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level | Week 10 | 7 Participants |
Secondary
Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks
Number of participants who required dose increase, dose reduce, dose interruption or dose resume were reported. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.
Time frame: Baseline up to Week 19
Population: Safety population included all participants who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Increased | 2 Participants |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Resume | 0 Participants |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Interrupted | 1 Participants |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Reduced | 3 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Increased | 5 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Interrupted | 5 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Resume | 3 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Reduced | 3 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Increased | 5 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Resume | 1 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Interrupted | 2 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Reduced | 5 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Resume | 0 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Reduced | 4 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Interrupted | 0 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Increased | 4 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Resume | 1 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Increased | 7 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Reduced | 4 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Interrupted | 1 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Interrupted | 0 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Increased | 1 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Resume | 0 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Reduced | 1 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Reduced | 6 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Interrupted | 3 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Increased | 8 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Resume | 1 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Resume | 8 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Increased | 12 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Reduced | 11 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks | Dose Interrupted | 9 Participants |
Secondary
Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only
Number of participants who required dose increase, dose reduce, dose interruption or dose resume were reported. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.
Time frame: Baseline up to Week 6
Population: Safety population included all participants who were randomized and received at least one dose of study medication. Here, 'Overall number of participants analyzed' signifies participants who were treated for 6 weeks only.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Increased | 0 Participants |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Reduced | 0 Participants |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Interrupted | 4 Participants |
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Resume | 0 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Increased | 3 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Resume | 6 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Reduced | 0 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Interrupted | 7 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Resume | 4 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Reduced | 0 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Interrupted | 4 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Increased | 0 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Increased | 0 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Reduced | 2 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Resume | 0 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Interrupted | 0 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Resume | 0 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Interrupted | 3 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Reduced | 6 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only | Dose Increased | 9 Participants |
Secondary
Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks
Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron.
Time frame: Baseline up to Week 19
Population: Safety population included all participants who were randomized and received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks | 4 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks | 2 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks | 3 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks | 2 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks | 3 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks | 0 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks | 4 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks | 4 Participants |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks | 3 Participants |
| Cohort B (Epoetin Alfa) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks | 0 Participants |
| Cohort B (Placebo) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks | 1 Participants |
Secondary
Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks
Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron.
Time frame: Baseline up to Week 6
Population: Safety population included all participants who were randomized and received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 2 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 2 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 3 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 4 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 2 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 3 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 2 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 3 Participants |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 0 Participants |
| Cohort B (Epoetin Alfa) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 4 Participants |
| Cohort B (Placebo) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 6 Participants |
| Cohort B-1 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 1 Participants |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 3 Participants |
| Cohort B (Epoetin Alfa) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 0 Participants |
| Cohort B (Placebo) | Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks | 1 Participants |
Secondary
Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks
Time frame: Week 7
Population: EE population for 19 weeks treatment included all participants randomized designated to receive 19 weeks of study medication and had received study treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion), or who permanently discontinued study medication during the dosing period due to lack of efficacy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks | 3 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks | 4 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks | 3 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks | 6 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks | 6 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks | 0 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks | 1 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks | 13 Participants |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks | 2 Participants |
| Cohort B (Epoetin Alfa) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks | 3 Participants |
| Cohort B (Placebo) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks | 0 Participants |
Secondary
Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks
Time frame: Week 7
Population: EE population included participants who received treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion) or who permanently discontinued study drug during dosing period due to lack of efficacy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 3 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 3 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 5 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 5 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 4 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 3 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 6 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 6 Participants |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 0 Participants |
| Cohort B (Epoetin Alfa) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 1 Participants |
| Cohort B (Placebo) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 19 Participants |
| Cohort B-1 (Roxadustat 1.5 mg/kg TIW) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 0 Participants |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 2 Participants |
| Cohort B (Epoetin Alfa) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 3 Participants |
| Cohort B (Placebo) | Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks | 0 Participants |
Secondary
Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks)
The average of the mean Hb values that were within 10-13 g/dL at Weeks 17, 18, 19, and 20 are presented. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants. LOCF method was used to impute missing values.
Time frame: Weeks 17, 18, 19, and 20
Population: EE population for 19 weeks treatment included all participants randomized designated to receive 19 weeks of study medication and had received study treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion), or who permanently discontinued study medication during the dosing period due to lack of efficacy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 5 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 2 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 10 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 10 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 7 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 2 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 6 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 19 Participants |
Secondary
Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks)
The average of the mean Hb values that were within 11-13 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.
Time frame: Weeks 17, 18, 19, and 20
Population: EE population for 19 weeks treatment included all participants randomized designated to receive 19 weeks of study medication and had received study treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion), or who permanently discontinued study medication during the dosing period due to lack of efficacy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 4 Participants |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 1 Participants |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 6 Participants |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 5 Participants |
| Cohort A (Epoetin Alfa) | Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 6 Participants |
| Cohort A-9 (Roxadustat 2.0 mg/kg) | Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 2 Participants |
| Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) | Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 3 Participants |
| Cohorts A (Epoetin Alfa) | Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 8 Participants |
| Cohort B-2 (Roxadustat 2.0 mg/kg TIW) | Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 0 Participants |
| Cohort B (Epoetin Alfa) | Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 0 Participants |
| Cohort B (Placebo) | Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) | 0 Participants |
Secondary
Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6
The rate of rise was computed as the slope of the regression line of change in Hb level (in g/dL) vs. time (in weeks) using Random Coefficient Model. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.
Time frame: Baseline up to Week 6
Population: EE included participants who received treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion) or who permanently discontinued study drug during dosing period due to lack of efficacy. Here, 'Overall number of participants analyzed' signifies participants who were treated for 6 weeks only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A-1 (Roxadustat 1.0 mg/kg TIW) | Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6 | -0.0135 g/dL/week |
| Cohort A-2 (Roxadustat 1.5 mg/kg TIW) | Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6 | 0.1926 g/dL/week |
| Cohort A-3 (Roxadustat 2.0 mg/kg TIW) | Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6 | 0.1682 g/dL/week |
| Cohort A-4 (Roxadustat 1.8 mg/kg TIW) | Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6 | -0.0220 g/dL/week |
| Cohort A (Epoetin Alfa) | Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6 | -0.1267 g/dL/week |
Secondary
Trough Plasma Concentration of Roxadustat and Epoetin Alfa
Time frame: Predose, 4, 8, 12, 24, 48, and 72 hours postdose at Weeks 1 and 6
Population: Data for trough plasma concentration of roxadustat and epoetin alfa were not collected for this study.