Anemia in Chronic Kidney Disease in Non-dialysis Patients
Conditions
Keywords
Non-dialysis, Roxadustat, ASP1517, Chronic Kidney Disease (CKD), Anemia, Hemoglobin
Brief summary
The primary objective of this study was to evaluate the efficacy of roxadustat compared to darbepoetin alfa in the treatment of anemia in nondialysis-dependent chronic kidney disease (NDD CKD) participants.
Detailed description
This was a phase 3, multicenter, randomized, open-label, active-controlled study. The study was planned to provide key efficacy and safety data for the approval of roxadustat in the treatment of anemia associated with CKD. Participants assigned to roxadustat treatment were administered roxadustat orally as a combination of tablets of different strengths. Participants assigned to darbepoetin alfa treatment were administered darbepoetin alfa subcutaneously or intravenously. The study consisted of 3 study periods: * Screening period: up to 6 weeks * Treatment period: 104 weeks * Follow-up period: 4 weeks until planned study end (end of year 2)
Interventions
DRUGRoxadustat
Oral tablet.
DRUGDarbepoetin alfa
Subcutaneous or intravenous injection.
Sponsors
Kyntra Bio
Astellas Pharma Europe B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has a diagnosis of CKD, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4 or 5, not on dialysis; with an Estimated Glomerular Filtration Rate (eGFR) \<60 mL/min/1.73 m\^2 estimated using the abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) equation. * The mean of the subject's two most recent (prior to randomization) Hb values during the screening period, obtained at least 4 days apart, must be less than or equal to 10.5 g/dL, with a difference of less than or equal to 1.0 g/dL. The last Hb value must be within 10 days prior to randomization. * Subject is deemed suitable for treatment with Erythropoiesis Stimulating Agent (ESA) using the criteria specified in the Kidney Disease Improving Global Outcomes (KDIGO) 2012 recommendation considering the rate of fall of Hb concentration, prior response to iron therapy, the risk of needing a transfusion, the risks related to ESA therapy and the presence of symptoms attributable to anemia. * Subject has a serum folate level greater than or equal to lower limit of normal (LLN) at screening. * Subject has a serum vitamin B12 level greater than or equal to LLN at screening. * Subject's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are less than or equal to 3 x upper limit of normal (ULN), and total bilirubin (TBL) is less than or equal to 1.5 x ULN. * Subject's body weight is 45.0 kg to a maximum of 160.0 kg. * Male subject must not donate sperm starting from screening, throughout the study period and up to 12 weeks after final study drug administration.
Exclusion criteria
* Subject has received any Erythropoiesis Stimulating Agent (ESA) treatment within 12 weeks prior to randomization. * Subject has received any dose of IV iron within 6 weeks prior to randomization. * Subject has received a Red Blood Cell (RBC) transfusion within 8 weeks prior to randomization. * Subject has a known history of myelodysplastic syndrome or multiple myeloma. * Subject has a known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than Chronic Kidney Disease (CKD). * Subject has a known hemosiderosis, hemochromatosis, coagulation disorder, or hypercoagulable condition. * Subject has a known chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission. * Subject is anticipated to undergo elective surgery that is expected to lead to significant blood loss during the study period or anticipated elective coronary revascularization. * Subject has active or chronic gastrointestinal bleeding. * Subject has received any prior treatment with roxadustat or a Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). * Subject has been treated with iron-chelating agents within 4 weeks prior to randomization. * Subject has a history of chronic liver disease (e.g., cirrhosis or fibrosis of the liver). * Subject has known New York Heart Association Class III or IV congestive heart failure. * Subject has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization. * Subject has one or more contraindications for treatment with darbepoetin alfa: * Uncontrolled hypertension, or two or more blood pressure values of SBP greater than or equal to 160 mmHg or DBP greater than or equal to 95 mmHg (within 2 weeks prior to randomization). * Known hypersensitivity to darbepoetin alfa, recombinant human erythropoietin, or any of the excipients. * Subject has a diagnosis or suspicion (e.g., complex kidney cyst of Bosniak Category 2F or higher) of renal cell carcinoma as shown on renal ultrasound within 12 weeks prior to randomization. * Subject has a history of malignancy, except for the following: cancers determined to be cured or in remission for greater than or equal to 5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps. * Subject is positive for any of the following: * human immunodeficiency virus (HIV). * hepatitis B surface antigen (HBsAg). * or anti-hepatitis C virus antibody (anti-HCV Ab). * Subject has an active clinically significant infection that is manifested by White Blood Count (WBC) \> Upper Limit of Normal (ULN), and/or fever, in conjunction with clinical signs or symptoms of infection within one week prior to randomization. * Subject has a known untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration or retinal vein occlusion. * Subject has had any prior organ transplant (that has not been explanted), subject is scheduled for organ transplantation, or subject is likely to initiate renal replacement therapy including dialysis within the first year of the study. * Subject will be excluded from participation if any of the following apply: * subject has received investigational therapy within 30 days or 5 half lives or limit set by national law, whichever is longer, prior to initiation of screening, or * any condition which makes the subject unsuitable for study participation. * Subject has an anticipated use of dapsone in any dose amount or chronic use of acetaminophen/paracetamol \>2.0 g/day during the treatment or follow-up period of the study. * Subject has a history of alcohol or drug abuse within 2 years prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Hb Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy | Baseline to week 24 | Hb response was measured as Yes or No. Response Yes (responders) was defined as: Hb ≥11.0 g/dL and Hb change from baseline by ≥ 1.0 g/dL, for participants with baseline Hb \> 8.0 g/dL; or Hb change from baseline by ≥ 2.0 g/dL, for participants with baseline Hb ≤ 8.0 g/dL at two consecutive visits with available data separated at least 5 days during the first 24 weeks of treatment without having received rescue therapy (red blood cell \[RBC\] transfusion for all participants or darbepoetin for roxadustat treated participant). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28 | Baseline and weeks 12 to 28 | Baseline LDL-C was defined as the LDL-C value on day 1. If this value was missing, the latest value prior to first study drug administration was used. |
| Time to First Intravenous Iron Use | Weeks 6, 12, 18, 24, 30 and 36 | Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to end of treatment (EOT) Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who had received more than one intravenous iron, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure. |
| Change From Baseline in Short Form-36 (SF-36) Physical Functioning (PF) Sub-Score to the Average PF Sub Score in Weeks 12 to 28 | Baseline and weeks 12 to 28 | Baseline SF-36 PF was defined as the SF-36 PF value on Day 1.The SF-36 is a Quality of Life (QoL) instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 contains 36 items that measured eight scales: (1) physical functioning; (2) role limitations due to physical health problems; (3) bodily pain; (4) social functioning; (5) general health perceptions; (6) role limitations due to emotional problems; (7) vitality, energy or fatigue; and (8) mental health. Each scale is transformed into 0-100 score, with higher scores indicating better health status. The SF-36 PF consisted of 11 questions that focused on health and ability to do usual activities, with higher scores indicating better health status. |
| Change From Baseline in SF-36 Vitality (VT) Sub-Score to the Average VT Sub-Score in Weeks 12 to 28 | Baseline and weeks 12 to 28 | Baseline VT Subscore was defined as the VT value on Day 1. The SF-36 is a QoL instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 vitality has four questions with score range from 0-100 with higher scores indicating better vitality status. |
| Change From Baseline in Mean Arterial Pressure (MAP) to the Average MAP Value in Weeks 20 to 28: Per Protocol Set | Baseline and weeks 20 to 28 | Baseline MAP was defined as the MAP value on Day 1. If this value was missing, the latest value prior to first study drug administration was used. MAP was derived as: MAP = (2/3)\*diastolic blood pressure (DBP) + (1/3)\*systolic blood pressure (SBP). |
| Time to First Occurrence of Hypertension During Weeks 1 to 36: Per Protocol Set | Weeks 1 to 36 | Hypertension was defined as either SBP ≥ 170 mmHg and an increase from baseline ≥ 20 mmHg or as DBP ≥ 110 mmHg and an increase from baseline ≥ 15 mmHg. For participants who had experienced more than one event, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion. Percentage of participants were reported in this outcome measure. |
| Change From Baseline in MAP to the Average MAP Value in Weeks 20 to 28: Full Analysis Set | Baseline and weeks 20 to 28 | Baseline MAP was defined as the MAP value on Day 1. If this value was missing, the latest value prior to first study drug administration was used. MAP was derived as: MAP = (2/3)\*DBP + (1/3)\*SBP. |
| Time to First Occurrence of Hypertension During Weeks 1 to 36: Full Analysis Set | Weeks 1 to 36 | Hypertension was defined as either SBP ≥ 170 mmHg and an increase from baseline ≥ 20 mmHg or as DBP ≥ 110 mmHg and an increase from baseline ≥ 15 mmHg. For participants who had experienced more than one event, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion. Percentage of participants were reported in this outcome measure. |
| Change From Baseline in Hb to the Average Hb Value of Weeks 28 to 52 Regardless of Rescue Therapy | Baseline and weeks 28 to 52 | Baseline Hb was defined as the mean of all available central laboratory Hb values collected before or including the date of first study drug intake (pre-dose). |
| Time to First Hb Response During First 24 Weeks of Treatment Regardless of Administration of Rescue Therapy | Weeks 1 to 24 | Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who had experienced more than one event, only their first event was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion. Percentage of participants were reported in this outcome measure. |
| Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins B (ApoB) | Baseline and weeks 8, 28, 52, 104 | Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
| Time to First Hb Response During First 24 Weeks of Treatment Without Rescue Therapy | Weeks 1 to 24 | Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who had experienced more than one event, only their first event was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion. Percentage of participants were reported in this outcome measure. |
| Hb Level Averaged Over Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 Without Rescue Therapy | Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 | Baseline Hb was defined as the mean of all available central laboratory Hb values collected before or including the date of first study drug intake (predose). |
| Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Baseline and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104 | Baseline Hb was defined as the mean of all available central laboratory Hb values collected before or including the date of first study drug intake (pre-dose). |
| Change From Baseline in Hb to Average Hb Value of Weeks 28 to 36, 44 to 52, 72 to 80, 96 to 104 Regardless of Use of Rescue Therapy | Baseline and weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 | Baseline Hb was defined as the mean of all available central laboratory Hb values collected before or including the date of first study drug intake (predose). |
| Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 28 to 36, 44 to 52 and 96 to 104 | Percentage for each participant was calculated from the number of Hb values within 10.0-12.0 g/dL / total number of Hb values\*100 in weeks 28 to 36, 44 to 52 and 96 to 104 without use of rescue therapy within 6 weeks prior to and during the 8 week evaluation period. |
| Time to First Hb Rate of Rise > 2 g/dL Within 4 Weeks | Year 0.5, 1, 1.5 and 2 | Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who had experienced more than one event, only their first event was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure. |
| Number of Hospitalizations | Baseline to EOT (up to week 104) | The number of hospitalizations per participant were calculated during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). |
| Number of Days of Hospitalization Per Year | Baseline to EOT (up to week 104) | The number of days of hospitalization per year was calculated as the sum of the durations of all hospitalizations in days (minimum \[date of discharge, end of efficacy of emergent period\] - date of admission + 1) / (duration of efficacy emergent period in days / 365.25). The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). |
| Time to First Hospitalization | Year 0.5, 1, 1.5 and 2 | Time to first hospitalization in years was defined in years as: (first event date during the efficacy emergent period - analysis date of first dose intake +1)/365.25, and the 'first event date' was defined as 'date of first admission and 'analysis date of first dose intake. Date of end of efficacy emergent period was defined as as the treatment period up to the EOT visit. For participants who have experienced more than one hospitalization, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure. |
| Change From Baseline to Weeks 8, 28, 52 and 104 in ApoB/ApoA1 Ratio | Baseline and weeks 8, 28, 52, 104 | Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
| Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12 to 28 and 36 to 52 | Missing category for fasting only includes non-fasting participants and the participants with missing values. |
| Time to First Use of RBC Transfusion | Year 0.5, 1, 1.5 and 2 | Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who had experienced more than one RBC transfusion, only their first event was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure. |
| Number of RBC Packs | Baseline to EOT (up to week 104) | The number of RBC packs were calculated as the sum of units transfused during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT visit or last non-missing Hb assessment (for participants who died during the treatment period). Participants with no medication records of RBC have their number of RBC packs set to 0. |
| Volume of RBC Transfused | Baseline to EOT (up to week 104) | The volume of blood transfused was calculated as the sum of blood volume transfused during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). Participants with no medication records of RBC have their volume set to 0. |
| Number of Particpants Who Received RBC Transfusions | Baseline to EOT (up to week 104) | Participants who received RBC transfusions during the efficacy emergent period were reported. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). |
| Time to First Use of Rescue Therapy | Year 0.5, 1, 1.5 and 2 | Rescue therapy for participants in the roxadustat group included RBC transfusion or ESA therapy and for participants in the darbepoetin alfa group included RBC transfusion only. Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who have experienced more than one use of rescue therapy (i.e. RBC and ESA), only their first event was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure. |
| Number of Participants Who Received Rescue Therapy (Composite of RBC Transfusions (All Participants) and Darbepoetin Alfa Use (Roxadustat Treated Participants Only) | Baseline to EOT (up to week 104) | Rescue therapy for participants in the roxadustat group included RBC transfusion or ESA therapy and for participants in the darbepoetin alfa group included RBC transfusion only. Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who have experienced more than one use of rescue therapy (i.e. RBC and ESA), only their first event was used. |
| Mean Monthly Intravenous Iron Per Participant During Weeks 37 to 52 and 53 to 104 | Weeks 37 to 52 and 53 to 104 | Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg. |
| Time to First Use of IV Iron Supplementation | Year 0.5, 1, 1.5 and 2 | Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who had received more than one IV iron, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure. |
| Percentage of Participants With Oral Iron Use Only | Day 1 to week 36, weeks 37 to 52, weeks 53 to 104, efficacy emergent period (up to week 104) | Percentage of participants with oral iron use only were calculated based on total number of participants within the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). |
| Change From Baseline to Weeks 8, 28, 52 and 104 in Total Cholesterol | Baseline and weeks 8, 28, 52, 104 | Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
| Change From Baseline to Weeks 8, 28, 52 and 104 in LDL-C/High-Density Lipoprotein Cholesterol (HDL-C) Ratio | Baseline and weeks 8, 28, 52, 104 | Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
| Change From Baseline to Weeks 8, 28, 52 and 104 in Non-HDL Cholesterol | Baseline and weeks 8, 28, 52, 104 | Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
| Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins A1 (ApoA1) | Baseline and weeks 8, 28, 52, 104 | Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
| Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Weeks 12 to 28 and 36 to 52 | Achieved antihypertensive treatment goal was defined as SBP \< 130 mmHg and DBP \< 80 mmHg over an evaluation period defined as the average of available values in weeks 12 to 28 and 36 to 52. |
| Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in SF-36 Physical Component Score (PCS) | Baseline, weeks 12 to 28 and 36 to 52 | Baseline SF-36 PCS was defined as the SF-36 PCS value on day 1.The SF-36 is a QoL instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 contains 36 items that measured eight scales: (1) physical functioning; (2) role limitations due to physical health problems; (3) bodily pain; (4) social functioning; (5) general health perceptions; (6) role limitations due to emotional problems; (7) vitality, energy or fatigue; and (8) mental health. Each scale is transformed into 0-100 score, with higher scores indicating better health status. The PCS was calculated based on all 8 scales and ranged from 5.02-79.78. For each of these above scales, higher scores always indicated better health status. |
| Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in Anemia Subscale (AnS) (Additional Concerns) of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score | Baseline, weeks 12 to 28 and 36 to 52 | Baseline FACT-An AnS was defined as the FACT-An AnS value on day 1. Together with the functional assessment of cancer therapy - general (FACT-G), the AnS is referred to as the FACT-An Total. The AnS scale contains 13 fatigue specific items (the fatigue score) plus 7 items related to anemia. The Anemia AnS score range is 0 to 80. Higher scores indicated better QoL. |
| Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Total Score | Baseline, weeks 12 to 28 and 36 to 52 | Baseline FACT-An total score was defined on day 1. Total Fact-An score is composed of FACT-G and Ans scales. FACT-G contains 27 items that cover four dimensions of well-being: physical well being (PWB) - 7 items, functional well being (FWB) - 7 items, social/family well being (SWB) - 7 items, and emotional well being (EWB) - 6 items. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia. The total score was obtained by summation of the scores from PWB, SWB, EWB, FWB and AnS. The FACT-An Total Score scale range was 0-188. A higher score indicated better QoL. |
| Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Trial Outcome Index (TOI) Score | Baseline, weeks 12 to 28 and 36 to 52 | Baseline FACT-An total TOI Score was defined on day 1. Total FACT-An TOI score is a sum of PWB subscale score, FWB subscale score and Ans scale score. Fact-An TOI scale contains 14 items that cover four dimensions of well-being: PWB -7 items, FWB -7 items, where score range for each PWB subscale and FWB subscale is 0-28. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia, where score range for Ans scale is 0-80. The total score was obtained by summation of the scores from PWB, FWB and AnS. The FACT-An Total TOI score range was 0-136. A higher score indicated better QoL. |
| Change From Baseline to the Average Value of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score | Baseline and weeks 12 to 28 | Baseline assessment was defined as the value on day 1. The EQ-5D-5L is a self-reported questionnaire, used as a measure of respondents' health related quality of life (HRQoL) and utility values. The EQ-5D consists of the descriptive system and the VAS. The EQ-5D descriptive system comprises 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, extreme problems. The VAS records the respondent's self rated health status on a graduated (0-100) scale, where the endpoints are labeled 'best imaginable health state' and 'worst imaginable health state' with higher scores for higher HRQoL. |
| Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in Work Productivity and Activity Impairment-Anemic Symptoms (WPAI:ANS) Score: Percent Work Time Missed | Baseline, weeks 12 to 28 and 36 to 52 | WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to anaemic symptoms; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the anaemic symptoms on productivity while working; Q6=Impact of the anaemic symptoms on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicated greater activity impairment. Multiply scores by 100 to express in percentages. Percent work time missed due to problem: Q2/(Q2+Q4). |
| Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Impairment While Working | Baseline, weeks 12 to 28 and 36 to 52 | WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to anaemic symptoms; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the anaemic symptoms on productivity while working; Q6=Impact of the anaemic symptoms on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicated greater activity impairment. Percent impairment while working due to problem: Q5/10. |
| Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Overall Work Impairment | Baseline, weeks 12 to 28 and 36 to 52 | WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to anaemic symptoms; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the anaemic symptoms on productivity while working; Q6=Impact of the anaemic symptoms on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicated greater activity impairment. Percent overall work impairment due to problem: Q2/(Q2+Q4)+\[(1-(Q2/(Q2+Q4))x(Q5/10)\]. |
| Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Activity Impairment | Baseline, weeks 12 to 28 and 36 to 52 | WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to anaemic symptoms; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the anaemic symptoms on productivity while working; Q6=Impact of the anaemic symptoms on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicated greater activity impairment. Percent activity impairment due to problem: Q6/10. |
| Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Weeks 8, 12, 28, 52, 76, 104, last assessment (week 108) | The PGIC is a patient-rated instrument that measured change in participant's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), when compared to the start of treatment. The percentage of participants presented included very much improved, much improved and minimally improved. |
| Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 and end of study (EOS) (up to 108 weeks) | Baseline assessment was assessment from day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
| Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 and EOS (up to 108 weeks) | Baseline assessment was assessment from day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
| Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Baseline and weeks 12, 28, 36, 44, 60, 84, 104 and EOS (up to 108 weeks) | Percentage of change from baseline to each study visit were calculated for HbA1c. Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
| Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104, 106 and EOS (up to 108 weeks) | Baseline assessment was assessment from day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
| Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104, 106 and EOS (up to 108 weeks) | Baseline assessment was assessment from day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
| Rate of Progression of Chronic Kidney Disease Measured by eGFR Slope Over Time | Baseline up to EOS (up to week 108) | Annualized eGFR slope over time was estimated by a random slopes and intercepts model using all available eGFR values (one baseline and all post-treatment values up to EOT period or start of dialysis adjusted on baseline Hb, region, CV history at baseline and the interaction terms (baseline eGFR by timepoint and baseline Hb by timepoint). All assessments collected after initiation of dialysis (acute or chronic) were excluded from the analysis. Baseline assessment was the assessment from day 1 visit. If this value was missing, the value from screening visit was used. |
| Change From Baseline in Hb to the Average Hb of Weeks 28 to 36 Without Rescue Therapy Within 6 Weeks Prior to and During This 8-Week Evaluation Period | Baseline and weeks 28 to 36 | Baseline Hb was defined as the mean of all available central laboratory Hb values collected before or including the date of first study drug intake (predose). |
| Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Year 0.5, 1, 1.5 and 2 | For participants who had doubled their serum creatinine or had chronic dialysis or renal transplant more than once, only their first occurrence during safety emergent period was used. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the end of treatment taking into account the different dosing frequencies of the study treatments. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure. |
| Number of Participants With End Stage Renal Disease (ESRD) | Baseline up to EOS (up to week 108) | Occurrence of end stage renal disease during the study (i.e from day 1 up to the end of study) was defined as at least one of the following: underwent \>30 days dialysis therapy, received kidney transplant, planned kidney transplant, physician recommended renal replacement therapy and participant refused therapy, began dialysis and died \< 30 days later. |
| Time to Chronic Kidney Disease Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Year 0.5, 1, 1.5 and 2 | Chronic kidney disease progression was defined as date of occurrence of chronic dialysis or date of renal transplant or doubled serum creatinine or date of death, whichever came first. For participants who had chronic dialysis or renal transplant or died, only their first occurrence during the safety emergent period was used. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the end of treatment taking into account the different dosing frequencies of the study treatments. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure. |
| Time to Chronic Dialysis or Renal Transplant or Death | Year 0.5, 1, 1.5 and 2 | For participants who had chronic dialysis or renal transplant or died, only their first occurrence during the safety emergent period was used. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the end of treatment taking into account the different dosing frequencies of the study treatments. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure. |
| Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Year 0.5, 1, 1.5 and 2 | For participants who had at least 40% decrease in eGFR from baseline, chronic dialysis or renal transplant during the safety emergent period, only their first occurrence was used. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the end of treatment taking into account the different dosing frequencies of the study treatments. Data reported was analyzed by kaplan-meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From first dose of study drug up to end of study (up to week 108) | An AE was defined as any untoward medical occurrence in a participant who was given the study drug or who had undergone study procedures and did not necessarily have a causal relationship with this treatment. All AEs collected during the safety emergent period were counted as TEAE. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the end of treatment taking into account the different dosing frequencies of the study treatments. Based on national cancer institute common terminology criteria (NCI-CTCAE), AEs were graded as grade 1=mild, grade 2=moderate, grade 3 =severe or medically significant, grade 4 =life threatening, grade 5 =death related to AE. All reported deaths after the first study drug administration and up to 28 days after the analysis date of last dose were based on last dosing frequency. |
| Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Baseline and weeks 12, 24, 36, 52, 64, 76, 88 and 104 | Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
Countries
Austria, Belarus, Bulgaria, Croatia, Czechia, Finland, France, Georgia, Germany, Hungary, Ireland, Israel, Latvia, Montenegro, Netherlands, North Macedonia, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Slovenia, Spain, Ukraine, United Kingdom
Participant flow
Recruitment details
Participants of ≥ 18 years of age with a diagnosis of chronic kidney disease, with kidney disease outcomes quality initiative stage 3, 4 or 5, anaemic and not receiving dialysis; with an estimated glomerular filtration rate (eGFR) \< 60 milliliter per minute per 1.73 meter square (mL/min/1.73 m\^2) were enrolled in this study.
Pre-assignment details
Participants were randomized in a 1:1 ratio to roxadustat or darbepoetin alfa. Randomization was stratified by 4 factors: region, screening hemoglobin (Hb) values (Hb ≤ 8.0 g/dL versus \> 8.0 g/dL), history of cardiovascular, cerebrovascular or thromboembolic diseases and screening eGFR (\<30 mL/min/1.73 m\^2 versus ≥30 mL/min/1.73 m\^2 ).
Participants by arm
| Arm | Count |
|---|---|
| Roxadustat Participants received roxadustat orally according to the tiered weight-based approach, with starting dose of 70 mg given TIW to participants weighing between 45 kg up to 70 kg and 100 mg given TIW to participants weighing more than 70 kg up to 160 kg. Dose-titration was performed based upon regular measurement of Hb levels until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL. Participants received roxadustat for up to a maximum of 104 weeks. | 323 |
| Darbepoetin Alfa Participants received initial dose of darbepoetin alfa based upon the weight (either 0.45 μg/kg of body weight, as a single subcutaneous or IV injection once weekly or 0.75 μg/kg of body weight, as a single subcutaneous injection once every 2 weeks) as per EU SmPC along with IV iron supplementation according to the standard of care. Dose-adjustment was performed based upon regular measurement of Hb levels until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which darbepoetin alfa dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL. Participants received darbepoetin alfa for up to a maximum of 104 weeks. | 293 |
| Total | 616 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Death | 33 | 34 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Miscellaneous | 2 | 3 |
| Overall Study | Physician Decision | 3 | 3 |
| Overall Study | Progressive Disease | 0 | 1 |
| Overall Study | Withdrawal by Subject | 30 | 18 |
Baseline characteristics
| Characteristic | Darbepoetin Alfa | Total | Roxadustat |
|---|---|---|---|
| Age, Continuous | 65.7 Years STANDARD_DEVIATION 14.4 | 66.3 Years STANDARD_DEVIATION 14 | 66.8 Years STANDARD_DEVIATION 13.6 |
| Baseline Hb Value <=8.0 g/dL | 10 Participants | 21 Participants | 11 Participants |
| Baseline Hb Value >8.0 g/dL | 283 Participants | 595 Participants | 312 Participants |
| Race/Ethnicity, Customized Race Asian | 10 Participants | 19 Participants | 9 Participants |
| Race/Ethnicity, Customized Race Black or African American | 2 Participants | 10 Participants | 8 Participants |
| Race/Ethnicity, Customized Race White | 281 Participants | 587 Participants | 306 Participants |
| Sex: Female, Male Female | 164 Participants | 342 Participants | 178 Participants |
| Sex: Female, Male Male | 129 Participants | 274 Participants | 145 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 40 / 323 | 37 / 293 |
| other Total, other adverse events | 223 / 323 | 203 / 293 |
| serious Total, serious adverse events | 209 / 323 | 181 / 293 |
Outcome results
Primary
Percentage of Participants With a Hb Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy
Hb response was measured as Yes or No. Response Yes (responders) was defined as: Hb ≥11.0 g/dL and Hb change from baseline by ≥ 1.0 g/dL, for participants with baseline Hb \> 8.0 g/dL; or Hb change from baseline by ≥ 2.0 g/dL, for participants with baseline Hb ≤ 8.0 g/dL at two consecutive visits with available data separated at least 5 days during the first 24 weeks of treatment without having received rescue therapy (red blood cell \[RBC\] transfusion for all participants or darbepoetin for roxadustat treated participant).
Time frame: Baseline to week 24
Population: The analysis population was the Per Protocol Set (PPS) which consisted of all Full Analysis Set (FAS) participants who did not meet any of exclusion criteria from the PPS. The FAS consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose valid Hb assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Percentage of Participants With a Hb Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy | 89.5 Percentage of Participants |
| Darbepoetin Alfa | Percentage of Participants With a Hb Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy | 78.0 Percentage of Participants |
Comparison: A generalized linear model as an approximation for the Miettinen and Nurminen method, adjusted for stratification factors (actual) was used to estimate the difference of proportions and 95% confidence interval.95% CI: [5.66, 17.36]
Secondary
Change From Baseline in Hb to Average Hb Value of Weeks 28 to 36, 44 to 52, 72 to 80, 96 to 104 Regardless of Use of Rescue Therapy
Baseline Hb was defined as the mean of all available central laboratory Hb values collected before or including the date of first study drug intake (predose).
Time frame: Baseline and weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Roxadustat | Change From Baseline in Hb to Average Hb Value of Weeks 28 to 36, 44 to 52, 72 to 80, 96 to 104 Regardless of Use of Rescue Therapy | Hb Change From BL to weeks 28-36 | 1.825 g/dL |
| Roxadustat | Change From Baseline in Hb to Average Hb Value of Weeks 28 to 36, 44 to 52, 72 to 80, 96 to 104 Regardless of Use of Rescue Therapy | Hb Change From BL to weeks 72-80 | 1.652 g/dL |
| Roxadustat | Change From Baseline in Hb to Average Hb Value of Weeks 28 to 36, 44 to 52, 72 to 80, 96 to 104 Regardless of Use of Rescue Therapy | Hb Change From BL to weeks 44-52 | 1.619 g/dL |
| Roxadustat | Change From Baseline in Hb to Average Hb Value of Weeks 28 to 36, 44 to 52, 72 to 80, 96 to 104 Regardless of Use of Rescue Therapy | Hb Change From BL to weeks 96-104 | 1.486 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Average Hb Value of Weeks 28 to 36, 44 to 52, 72 to 80, 96 to 104 Regardless of Use of Rescue Therapy | Hb Change From BL to weeks 44-52 | 1.62 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Average Hb Value of Weeks 28 to 36, 44 to 52, 72 to 80, 96 to 104 Regardless of Use of Rescue Therapy | Hb Change From BL to weeks 28-36 | 1.799 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Average Hb Value of Weeks 28 to 36, 44 to 52, 72 to 80, 96 to 104 Regardless of Use of Rescue Therapy | Hb Change From BL to weeks 96-104 | 1.502 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Average Hb Value of Weeks 28 to 36, 44 to 52, 72 to 80, 96 to 104 Regardless of Use of Rescue Therapy | Hb Change From BL to weeks 72-80 | 1.649 g/dL |
Comparison: Weeks 28-36 - The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline estimated glomerular filtration rate and baseline Hb by visit as continuous covariates.p-value: 0.72795% CI: [-0.119, 0.17]Mixed Models Analysis
Comparison: Weeks 44-52 - The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline estimated glomerular filtration rate and baseline Hb by visit as continuous covariates.p-value: 0.98595% CI: [-0.151, 0.148]Mixed Models Analysis
Comparison: Weeks 72-80 - The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline estimated glomerular filtration rate and baseline Hb by visit as continuous covariates.p-value: 0.96595% CI: [-0.148, 0.154]Mixed Models Analysis
Comparison: Weeks 96-104 - The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline estimated glomerular filtration rate and baseline Hb by visit as continuous covariates.p-value: 0.85695% CI: [-0.188, 0.157]Mixed Models Analysis
Secondary
Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy
Baseline Hb was defined as the mean of all available central laboratory Hb values collected before or including the date of first study drug intake (pre-dose).
Time frame: Baseline and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 68 | 1.851 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 2 | 0.862 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 6 | 1.845 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 12 | 2.33 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 16 | 2.177 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 18 | 1.783 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 20 | 1.986 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 22 | 1.584 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 24 | 1.493 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 32 | 1.687 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to Week 36 | 1.913 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 56 | 1.412 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 60 | 1.735 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 80 | 1.534 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 84 | 1.723 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 88 | 1.424 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 72 | 1.615 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 76 | 1.745 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 92 | 1.677 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 96 | 1.429 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 100 | 1.488 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 104 | 1.489 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 4 | 1.508 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 8 | 2.063 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 10 | 1.941 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 14 | 1.904 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 28 | 1.803 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 40 | 1.625 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 44 | 1.65 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 48 | 1.459 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 52 | 1.682 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 64 | 1.546 g/dL |
| Roxadustat | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 1 | 0.381 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 64 | 1.547 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 1 | 0.294 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 72 | 1.548 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 2 | 0.584 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 4 | 1.073 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 44 | 1.628 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 6 | 1.423 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 10 | 1.611 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 76 | 1.767 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 12 | 2.03 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 88 | 1.37 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 16 | 1.994 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 14 | 1.745 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 18 | 1.609 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 92 | 1.643 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 20 | 1.9 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 22 | 1.615 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 96 | 1.404 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 24 | 1.554 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 52 | 1.71 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 32 | 1.673 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 100 | 1.598 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to Week 36 | 1.781 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 28 | 1.869 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 56 | 1.444 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 104 | 1.452 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 60 | 1.67 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 48 | 1.447 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 80 | 1.579 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 40 | 1.438 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 84 | 1.679 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 8 | 1.682 g/dL |
| Darbepoetin Alfa | Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy | Hb Change From BL to week 68 | 1.747 g/dL |
Comparison: Week 1- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.08695% CI: [-0.012, 0.185]Mixed Models Analysis
Comparison: Week 2- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: <0.00195% CI: [0.165, 0.391]Mixed Models Analysis
Comparison: Week 4- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: <0.00195% CI: [0.284, 0.586]Mixed Models Analysis
Comparison: Week 6- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: <0.00195% CI: [0.254, 0.59]Mixed Models Analysis
Comparison: Week 8- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: <0.00195% CI: [0.205, 0.556]Mixed Models Analysis
Comparison: Week 10- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: <0.00195% CI: [0.155, 0.505]Mixed Models Analysis
Comparison: Week 12- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.00195% CI: [0.119, 0.482]Mixed Models Analysis
Comparison: Week 14- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.07995% CI: [-0.018, 0.336]Mixed Models Analysis
Comparison: Week 16- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.04495% CI: [0.005, 0.361]Mixed Models Analysis
Comparison: Week 18- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.03795% CI: [0.01, 0.336]Mixed Models Analysis
Comparison: Week 20- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.31995% CI: [-0.083, 0.253]Mixed Models Analysis
Comparison: Week 22- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.70995% CI: [-0.19, 0.129]Mixed Models Analysis
Comparison: Week 24- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.4595% CI: [-0.219, 0.097]Mixed Models Analysis
Comparison: Week 28- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.4495% CI: [-0.231, 0.101]Mixed Models Analysis
Comparison: Week 32- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.87495% CI: [-0.157, 0.184]Mixed Models Analysis
Comparison: Week 36- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.13295% CI: [-0.039, 0.302]Mixed Models Analysis
Comparison: Week 40- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.02495% CI: [0.024, 0.351]Mixed Models Analysis
Comparison: Week 44- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.80795% CI: [-0.153, 0.197]Mixed Models Analysis
Comparison: Week 48- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.8995% CI: [-0.16, 0.185]Mixed Models Analysis
Comparison: Week 52- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.74695% CI: [-0.201, 0.144]Mixed Models Analysis
Comparison: Week 56- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.71595% CI: [-0.202, 0.139]Mixed Models Analysis
Comparison: Week 60- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.46395% CI: [-0.11, 0.242]Mixed Models Analysis
Comparison: Week 64- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.98795% CI: [-0.187, 0.184]Mixed Models Analysis
Comparison: Week 68- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.25195% CI: [-0.074, 0.281]Mixed Models Analysis
Comparison: Week 72- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.47395% CI: [-0.117, 0.251]Mixed Models Analysis
Comparison: Week 76- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.81395% CI: [-0.204, 0.16]Mixed Models Analysis
Comparison: Week 80- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.62295% CI: [-0.223, 0.134]Mixed Models Analysis
Comparison: Week 84- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.63295% CI: [-0.138, 0.227]Mixed Models Analysis
Comparison: Week 88- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.56895% CI: [-0.133, 0.242]Mixed Models Analysis
Comparison: Week 92- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.72995% CI: [-0.158, 0.226]Mixed Models Analysis
Comparison: Week 96- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.79795% CI: [-0.168, 0.218]Mixed Models Analysis
Comparison: Week 100- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.2895% CI: [-0.31, 0.09]Mixed Models Analysis
Comparison: Week 104- The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.73395% CI: [-0.177, 0.251]Mixed Models Analysis
Secondary
Change From Baseline in Hb to the Average Hb of Weeks 28 to 36 Without Rescue Therapy Within 6 Weeks Prior to and During This 8-Week Evaluation Period
Baseline Hb was defined as the mean of all available central laboratory Hb values collected before or including the date of first study drug intake (predose).
Time frame: Baseline and weeks 28 to 36
Population: The analysis population was the PPS, with participants who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Change From Baseline in Hb to the Average Hb of Weeks 28 to 36 Without Rescue Therapy Within 6 Weeks Prior to and During This 8-Week Evaluation Period | 1.848 g/dL | Standard Deviation 1.079 |
| Darbepoetin Alfa | Change From Baseline in Hb to the Average Hb of Weeks 28 to 36 Without Rescue Therapy Within 6 Weeks Prior to and During This 8-Week Evaluation Period | 1.839 g/dL | Standard Deviation 0.973 |
Comparison: The model included treatment, visit, visit by treatment interaction, region and history of cardiovascular disease as fixed class factors and baseline Hb, baseline estimated glomerular filtration rate and baseline Hb by visit as continuous covariates.p-value: 0.83995% CI: [-0.131, 0.162]Mixed Models Analysis
Secondary
Change From Baseline in Hb to the Average Hb Value of Weeks 28 to 52 Regardless of Rescue Therapy
Baseline Hb was defined as the mean of all available central laboratory Hb values collected before or including the date of first study drug intake (pre-dose).
Time frame: Baseline and weeks 28 to 52
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Change From Baseline in Hb to the Average Hb Value of Weeks 28 to 52 Regardless of Rescue Therapy | 1.718 g/dL | Standard Deviation 0.958 |
| Darbepoetin Alfa | Change From Baseline in Hb to the Average Hb Value of Weeks 28 to 52 Regardless of Rescue Therapy | 1.673 g/dL | Standard Deviation 0.923 |
Comparison: The model included treatment, visit, visit by treatment interaction, region and history of cardiovascular disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit as continuous covariates.p-value: 0.52995% CI: [-0.081, 0.157]Mixed Models Analysis
Secondary
Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28
Baseline LDL-C was defined as the LDL-C value on day 1. If this value was missing, the latest value prior to first study drug administration was used.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28 | -0.352 Millimoles per liter (mmol/L) | Standard Deviation 0.772 |
| Darbepoetin Alfa | Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28 | 0.049 Millimoles per liter (mmol/L) | Standard Deviation 0.705 |
Comparison: The model included treatment, visit, visit by treatment interaction, region and history of cardiovascular disease as fixed class factors and baseline LDL, baseline Hb, baseline estimated glomerular filtration rate as continuous covariates.p-value: <0.00195% CI: [-0.51, -0.296]Mixed Models Analysis
Secondary
Change From Baseline in MAP to the Average MAP Value in Weeks 20 to 28: Full Analysis Set
Baseline MAP was defined as the MAP value on Day 1. If this value was missing, the latest value prior to first study drug administration was used. MAP was derived as: MAP = (2/3)\*DBP + (1/3)\*SBP.
Time frame: Baseline and weeks 20 to 28
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Change From Baseline in MAP to the Average MAP Value in Weeks 20 to 28: Full Analysis Set | 0.635 mmHg | Standard Deviation 8.529 |
| Darbepoetin Alfa | Change From Baseline in MAP to the Average MAP Value in Weeks 20 to 28: Full Analysis Set | 0.457 mmHg | Standard Deviation 8.741 |
Comparison: The model included treatment, visit, visit by treatment interaction, region and history of cardiovascular disease as fixed class factors and baseline MAP, baseline Hb, baseline eGFR as continuous covariates.p-value: 0.81895% CI: [-1.299, 1.026]Mixed Models Analysis
Secondary
Change From Baseline in Mean Arterial Pressure (MAP) to the Average MAP Value in Weeks 20 to 28: Per Protocol Set
Baseline MAP was defined as the MAP value on Day 1. If this value was missing, the latest value prior to first study drug administration was used. MAP was derived as: MAP = (2/3)\*diastolic blood pressure (DBP) + (1/3)\*systolic blood pressure (SBP).
Time frame: Baseline and weeks 20 to 28
Population: The analysis population was the PPS, with participants who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Change From Baseline in Mean Arterial Pressure (MAP) to the Average MAP Value in Weeks 20 to 28: Per Protocol Set | 0.541 Millimeters of mercury (mmHg) | Standard Deviation 8.549 |
| Darbepoetin Alfa | Change From Baseline in Mean Arterial Pressure (MAP) to the Average MAP Value in Weeks 20 to 28: Per Protocol Set | 0.588 Millimeters of mercury (mmHg) | Standard Deviation 8.779 |
Comparison: The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline MAP, baseline Hb, baseline eGFR as continuous covariates.p-value: 0.54795% CI: [-1.587, 0.842]Mixed Models Analysis
Secondary
Change From Baseline in SF-36 Vitality (VT) Sub-Score to the Average VT Sub-Score in Weeks 12 to 28
Baseline VT Subscore was defined as the VT value on Day 1. The SF-36 is a QoL instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 vitality has four questions with score range from 0-100 with higher scores indicating better vitality status.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the PPS, with participants who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Change From Baseline in SF-36 Vitality (VT) Sub-Score to the Average VT Sub-Score in Weeks 12 to 28 | 4.077 Units on a scale | Standard Deviation 8.657 |
| Darbepoetin Alfa | Change From Baseline in SF-36 Vitality (VT) Sub-Score to the Average VT Sub-Score in Weeks 12 to 28 | 3.881 Units on a scale | Standard Deviation 8.76 |
Comparison: The model included treatment, visit (weeks 8, 12 and 28), visit by treatment interaction, region and history of cardiovascular disease as fixed class factors and baseline SF-36 VT, baseline Hb, baseline eGFR as continuous covariates.p-value: 0.45495% CI: [-1.656, 0.742]Mixed Models Analysis
Secondary
Change From Baseline in Short Form-36 (SF-36) Physical Functioning (PF) Sub-Score to the Average PF Sub Score in Weeks 12 to 28
Baseline SF-36 PF was defined as the SF-36 PF value on Day 1.The SF-36 is a Quality of Life (QoL) instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 contains 36 items that measured eight scales: (1) physical functioning; (2) role limitations due to physical health problems; (3) bodily pain; (4) social functioning; (5) general health perceptions; (6) role limitations due to emotional problems; (7) vitality, energy or fatigue; and (8) mental health. Each scale is transformed into 0-100 score, with higher scores indicating better health status. The SF-36 PF consisted of 11 questions that focused on health and ability to do usual activities, with higher scores indicating better health status.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the PPS, with participants who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Change From Baseline in Short Form-36 (SF-36) Physical Functioning (PF) Sub-Score to the Average PF Sub Score in Weeks 12 to 28 | 0.913 Units on a scale | Standard Deviation 7.182 |
| Darbepoetin Alfa | Change From Baseline in Short Form-36 (SF-36) Physical Functioning (PF) Sub-Score to the Average PF Sub Score in Weeks 12 to 28 | 2.062 Units on a scale | Standard Deviation 7.838 |
Comparison: The model included treatment, visit (weeks 8, 12 and 28) visit by treatment interaction, region and history of cardiovascular disease as fixed class factors and baseline SF-36 PF, baseline Hb, baseline estimated glomerular filtration rate as continuous covariates.p-value: 0.02795% CI: [-2.423, -0.145]Mixed Models Analysis
Secondary
Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR)
Baseline assessment was assessment from day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time frame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104, 106 and EOS (up to 108 weeks)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 4 | 1.01 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 8 | 1.01 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 20 | 0.98 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 52 | 0.90 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 68 | 0.87 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 100 | 0.84 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 12 | 1.02 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 28 | 0.93 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 36 | 0.93 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 44 | 0.90 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 60 | 0.90 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 76 | 0.83 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 84 | 0.83 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 92 | 0.84 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 104 | 0.84 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 106 | 0.84 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | EOS | 0.86 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 84 | 0.83 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 4 | 0.97 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 36 | 0.89 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 8 | 0.96 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 12 | 0.95 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | EOS | 0.85 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 20 | 0.93 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 44 | 0.89 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 92 | 0.85 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 52 | 0.88 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 60 | 0.86 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 68 | 0.84 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 106 | 0.86 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 100 | 0.86 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 76 | 0.84 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 104 | 0.84 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) | Week 28 | 0.89 Geometric mean ratio |
Secondary
Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose
Baseline assessment was assessment from day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time frame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104, 106 and EOS (up to 108 weeks)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 100 | 2.7 mg/dL | Standard Deviation 45.3 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 60 | 6.6 mg/dL | Standard Deviation 65.6 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 28 | 8.7 mg/dL | Standard Deviation 66.9 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 68 | 3.8 mg/dL | Standard Deviation 66.1 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 8 | 4.1 mg/dL | Standard Deviation 60.1 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 76 | 0.9 mg/dL | Standard Deviation 41.9 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 36 | 6.4 mg/dL | Standard Deviation 52.5 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 84 | 1.4 mg/dL | Standard Deviation 49.1 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 4 | 7 mg/dL | Standard Deviation 62.8 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 92 | 6 mg/dL | Standard Deviation 69.5 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 44 | 3.3 mg/dL | Standard Deviation 44.7 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 104 | -2.6 mg/dL | Standard Deviation 60.7 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 20 | 6.9 mg/dL | Standard Deviation 69.4 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 106 | -2.4 mg/dL | Standard Deviation 31.2 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 52 | 7.1 mg/dL | Standard Deviation 69.7 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | EOS | 2.5 mg/dL | Standard Deviation 58.2 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 12 | 9.3 mg/dL | Standard Deviation 64.5 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | EOS | 9.8 mg/dL | Standard Deviation 43.6 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 12 | 7.1 mg/dL | Standard Deviation 58.2 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 92 | 2.1 mg/dL | Standard Deviation 46.5 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 4 | 10.3 mg/dL | Standard Deviation 76.9 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 8 | 1.3 mg/dL | Standard Deviation 40.3 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 20 | 4.3 mg/dL | Standard Deviation 57.9 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 28 | 2.8 mg/dL | Standard Deviation 37.7 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 36 | 3.6 mg/dL | Standard Deviation 45.3 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 44 | 0.4 mg/dL | Standard Deviation 45.1 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 52 | 1.1 mg/dL | Standard Deviation 41.1 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 60 | 6.3 mg/dL | Standard Deviation 43.1 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 68 | 5.5 mg/dL | Standard Deviation 48.2 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 76 | 5.8 mg/dL | Standard Deviation 55.2 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 84 | 12 mg/dL | Standard Deviation 57.4 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 100 | 4 mg/dL | Standard Deviation 48.9 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 104 | 1 mg/dL | Standard Deviation 48.6 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose | Week 106 | 9.2 mg/dL | Standard Deviation 53.3 |
Secondary
Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c)
Percentage of change from baseline to each study visit were calculated for HbA1c. Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time frame: Baseline and weeks 12, 28, 36, 44, 60, 84, 104 and EOS (up to 108 weeks)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 28 | 0.0009 Percentage of HbA1c | Standard Deviation 0.0072 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 36 | 0.0021 Percentage of HbA1c | Standard Deviation 0.0075 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 84 | 0.0024 Percentage of HbA1c | Standard Deviation 0.0093 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 12 | 0.0021 Percentage of HbA1c | Standard Deviation 0.0071 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 44 | 0.0026 Percentage of HbA1c | Standard Deviation 0.0077 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 60 | 0.0025 Percentage of HbA1c | Standard Deviation 0.0083 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 104 | 0.0018 Percentage of HbA1c | Standard Deviation 0.0086 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | EOS | 0.0031 Percentage of HbA1c | Standard Deviation 0.0087 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | EOS | 0.0034 Percentage of HbA1c | Standard Deviation 0.0081 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 28 | 0.0015 Percentage of HbA1c | Standard Deviation 0.0067 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 44 | 0.002 Percentage of HbA1c | Standard Deviation 0.0066 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 36 | 0.0021 Percentage of HbA1c | Standard Deviation 0.0073 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 60 | 0.0019 Percentage of HbA1c | Standard Deviation 0.0074 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 104 | 0.002 Percentage of HbA1c | Standard Deviation 0.008 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 84 | 0.0025 Percentage of HbA1c | Standard Deviation 0.0077 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) | Week 12 | 0.001 Percentage of HbA1c | Standard Deviation 0.0073 |
Secondary
Change From Baseline to Each Scheduled Measurement in Serum Ferritin
Baseline assessment was assessment from day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time frame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 and end of study (EOS) (up to 108 weeks)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 100 | -95.513 Picomoles per liter (pmol/L) | Standard Deviation 486.758 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | EOS | 78.577 Picomoles per liter (pmol/L) | Standard Deviation 680.524 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 36 | -131.801 Picomoles per liter (pmol/L) | Standard Deviation 355.463 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 4 | -190.762 Picomoles per liter (pmol/L) | Standard Deviation 241.695 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 12 | -205.722 Picomoles per liter (pmol/L) | Standard Deviation 271.752 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 8 | -229.471 Picomoles per liter (pmol/L) | Standard Deviation 255.677 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 68 | -110.907 Picomoles per liter (pmol/L) | Standard Deviation 422.28 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 28 | -97.622 Picomoles per liter (pmol/L) | Standard Deviation 366.153 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 44 | -120.864 Picomoles per liter (pmol/L) | Standard Deviation 368.902 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 60 | -141.264 Picomoles per liter (pmol/L) | Standard Deviation 355.419 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 76 | -99.697 Picomoles per liter (pmol/L) | Standard Deviation 412.982 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 20 | -99.86 Picomoles per liter (pmol/L) | Standard Deviation 334.486 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 84 | -126.615 Picomoles per liter (pmol/L) | Standard Deviation 403.693 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 92 | -98.025 Picomoles per liter (pmol/L) | Standard Deviation 460.364 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 104 | -89.276 Picomoles per liter (pmol/L) | Standard Deviation 476.167 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 52 | -93.074 Picomoles per liter (pmol/L) | Standard Deviation 521.433 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 104 | 26.454 Picomoles per liter (pmol/L) | Standard Deviation 730.126 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 12 | -201.587 Picomoles per liter (pmol/L) | Standard Deviation 346.59 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 36 | -120.424 Picomoles per liter (pmol/L) | Standard Deviation 362.08 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 44 | -60.149 Picomoles per liter (pmol/L) | Standard Deviation 425.455 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 52 | -72.383 Picomoles per liter (pmol/L) | Standard Deviation 459.342 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 60 | -47.714 Picomoles per liter (pmol/L) | Standard Deviation 459.319 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 68 | -14.283 Picomoles per liter (pmol/L) | Standard Deviation 464.714 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 84 | -1.351 Picomoles per liter (pmol/L) | Standard Deviation 576.437 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 92 | -26.73 Picomoles per liter (pmol/L) | Standard Deviation 547.371 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | EOS | 119.157 Picomoles per liter (pmol/L) | Standard Deviation 697.39 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 4 | -159.174 Picomoles per liter (pmol/L) | Standard Deviation 218.981 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 20 | -140.26 Picomoles per liter (pmol/L) | Standard Deviation 338.512 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 28 | -121.574 Picomoles per liter (pmol/L) | Standard Deviation 348.136 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 76 | 3.424 Picomoles per liter (pmol/L) | Standard Deviation 615.735 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 100 | 31.391 Picomoles per liter (pmol/L) | Standard Deviation 750.432 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Serum Ferritin | Week 8 | -208.356 Picomoles per liter (pmol/L) | Standard Deviation 309.893 |
Secondary
Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT)
Baseline assessment was assessment from day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time frame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 and EOS (up to 108 weeks)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 12 | -2.4 Percentage of saturation | Standard Deviation 13.2 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 52 | 1.3 Percentage of saturation | Standard Deviation 11.8 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 68 | 1 Percentage of saturation | Standard Deviation 13.4 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 60 | 0.4 Percentage of saturation | Standard Deviation 12.4 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 76 | 0.1 Percentage of saturation | Standard Deviation 12.2 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 20 | 1.6 Percentage of saturation | Standard Deviation 13.9 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 84 | 1.1 Percentage of saturation | Standard Deviation 12.5 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 8 | -5.9 Percentage of saturation | Standard Deviation 11.5 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 92 | -0.2 Percentage of saturation | Standard Deviation 11.7 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 28 | 1.1 Percentage of saturation | Standard Deviation 12.5 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 100 | 0.6 Percentage of saturation | Standard Deviation 12.4 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 44 | 0.6 Percentage of saturation | Standard Deviation 12 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 104 | 0.5 Percentage of saturation | Standard Deviation 11.9 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 36 | 1.6 Percentage of saturation | Standard Deviation 12 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | EOS | 5.3 Percentage of saturation | Standard Deviation 12.3 |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 4 | -6 Percentage of saturation | Standard Deviation 10.7 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | EOS | 4.7 Percentage of saturation | Standard Deviation 13.9 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 4 | -2.1 Percentage of saturation | Standard Deviation 11.5 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 44 | 4.9 Percentage of saturation | Standard Deviation 12.9 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 60 | 4.8 Percentage of saturation | Standard Deviation 12.7 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 68 | 6.3 Percentage of saturation | Standard Deviation 13.1 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 8 | -2.4 Percentage of saturation | Standard Deviation 10.6 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 12 | -0.5 Percentage of saturation | Standard Deviation 12.3 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 20 | 2.9 Percentage of saturation | Standard Deviation 11.6 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 28 | 4 Percentage of saturation | Standard Deviation 12.5 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 36 | 3.9 Percentage of saturation | Standard Deviation 11.5 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 52 | 5.2 Percentage of saturation | Standard Deviation 13.2 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 76 | 6 Percentage of saturation | Standard Deviation 13.7 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 84 | 6.5 Percentage of saturation | Standard Deviation 13.9 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 92 | 5.6 Percentage of saturation | Standard Deviation 13.8 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 100 | 5.8 Percentage of saturation | Standard Deviation 14 |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) | Week 104 | 5 Percentage of saturation | Standard Deviation 13.3 |
Secondary
Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR)
Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time frame: Baseline and weeks 12, 24, 36, 52, 64, 76, 88 and 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 36 | 1.22 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 52 | 1.28 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 64 | 1.23 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 12 | 1.19 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 24 | 1.18 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 76 | 1.39 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 88 | 1.21 Geometric mean ratio |
| Roxadustat | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 104 | 1.46 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 24 | 1.22 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 36 | 1.18 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 52 | 1.1 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 64 | 1.11 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 104 | 1.18 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 88 | 1.1 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 12 | 1.23 Geometric mean ratio |
| Darbepoetin Alfa | Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) | Week 76 | 1.18 Geometric mean ratio |
Secondary
Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in Anemia Subscale (AnS) (Additional Concerns) of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score
Baseline FACT-An AnS was defined as the FACT-An AnS value on day 1. Together with the functional assessment of cancer therapy - general (FACT-G), the AnS is referred to as the FACT-An Total. The AnS scale contains 13 fatigue specific items (the fatigue score) plus 7 items related to anemia. The Anemia AnS score range is 0 to 80. Higher scores indicated better QoL.
Time frame: Baseline, weeks 12 to 28 and 36 to 52
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Roxadustat | Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in Anemia Subscale (AnS) (Additional Concerns) of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score | Change from BL to weeks 12-28 | 4.71 Units on a scale |
| Roxadustat | Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in Anemia Subscale (AnS) (Additional Concerns) of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score | Change from BL to weeks 36-52 | 3.661 Units on a scale |
| Darbepoetin Alfa | Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in Anemia Subscale (AnS) (Additional Concerns) of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score | Change from BL to weeks 12-28 | 5.238 Units on a scale |
| Darbepoetin Alfa | Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in Anemia Subscale (AnS) (Additional Concerns) of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score | Change from BL to weeks 36-52 | 4.608 Units on a scale |
Comparison: Weeks 12-28 - The model included treatment, visit, visit by treatment interaction, region and history of cardiovascular disease as fixed class factors and baseline FACT-An AnS, baseline Hb, baseline estimated glomerular filtration rate as continuous covariates.p-value: 0.51795% CI: [-2.127, 1.072]Mixed Models Analysis
Comparison: Weeks 36-52 - The model included treatment, visit, visit by treatment interaction, region and history of cardiovascular disease as fixed class factors and baseline FACT-An AnS, baseline Hb, baseline estimated glomerular filtration rate as continuous covariates.p-value: 0.30895% CI: [-2.771, 0.877]Mixed Models Analysis
Secondary
Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in SF-36 Physical Component Score (PCS)
Baseline SF-36 PCS was defined as the SF-36 PCS value on day 1.The SF-36 is a QoL instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 contains 36 items that measured eight scales: (1) physical functioning; (2) role limitations due to physical health problems; (3) bodily pain; (4) social functioning; (5) general health perceptions; (6) role limitations due to emotional problems; (7) vitality, energy or fatigue; and (8) mental health. Each scale is transformed into 0-100 score, with higher scores indicating better health status. The PCS was calculated based on all 8 scales and ranged from 5.02-79.78. For each of these above scales, higher scores always indicated better health status.
Time frame: Baseline, weeks 12 to 28 and 36 to 52
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Roxadustat | Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in SF-36 Physical Component Score (PCS) | Change from BL to weeks 12-28 | 1.222 Units on a scale |
| Roxadustat | Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in SF-36 Physical Component Score (PCS) | Change from BL to weeks 36-52 | 1.083 Units on a scale |
| Darbepoetin Alfa | Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in SF-36 Physical Component Score (PCS) | Change from BL to weeks 12-28 | 2.29 Units on a scale |
| Darbepoetin Alfa | Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in SF-36 Physical Component Score (PCS) | Change from BL to weeks 36-52 | 1.686 Units on a scale |
Comparison: Weeks 12-28 - The model included treatment, visit, visit by treatment interaction, region and history of cardiovascular disease as fixed class factors and baseline SF-36 PCS, baseline Hb, baseline estimated glomerular filtration rate as continuous covariates.p-value: 0.02795% CI: [-2.012, -0.124]Mixed Models Analysis
Comparison: Weeks 36-52 - The model included treatment, visit, visit by treatment interaction, region and history of cardiovascular disease as fixed class factors and baseline SF-36 PCS, baseline Hb, baseline estimated glomerular filtration rate as continuous covariates.p-value: 0.23995% CI: [-1.606, 0.401]Mixed Models Analysis
Secondary
Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Total Score
Baseline FACT-An total score was defined on day 1. Total Fact-An score is composed of FACT-G and Ans scales. FACT-G contains 27 items that cover four dimensions of well-being: physical well being (PWB) - 7 items, functional well being (FWB) - 7 items, social/family well being (SWB) - 7 items, and emotional well being (EWB) - 6 items. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia. The total score was obtained by summation of the scores from PWB, SWB, EWB, FWB and AnS. The FACT-An Total Score scale range was 0-188. A higher score indicated better QoL.
Time frame: Baseline, weeks 12 to 28 and 36 to 52
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Total Score | Change from BL to weeks 12-28 | 7.761 Units on a scale |
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Total Score | Change from BL to weeks 36-52 | 5.492 Units on a scale |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Total Score | Change from BL to weeks 12-28 | 8.665 Units on a scale |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Total Score | Change from BL to weeks 36-52 | 7.259 Units on a scale |
Comparison: Week 12-28 - The model included treatment, visit, visit by treatment interaction, region and history of cardiovascular disease as fixed class factors and baseline FACT-An total score, baseline Hb, baseline estimated glomerular filtration rate as continuous covariates.p-value: 0.5795% CI: [-4.032, 2.224]Mixed Models Analysis
Comparison: Weeks 36-52 -The model included treatment, visit, visit by treatment interaction, region and history of cardiovascular disease as fixed class factors and baseline FACT-An total score, baseline Hb, baseline estimated glomerular filtration rate as continuous covariates.p-value: 0.33495% CI: [-5.354, 1.82]Mixed Models Analysis
Secondary
Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Trial Outcome Index (TOI) Score
Baseline FACT-An total TOI Score was defined on day 1. Total FACT-An TOI score is a sum of PWB subscale score, FWB subscale score and Ans scale score. Fact-An TOI scale contains 14 items that cover four dimensions of well-being: PWB -7 items, FWB -7 items, where score range for each PWB subscale and FWB subscale is 0-28. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia, where score range for Ans scale is 0-80. The total score was obtained by summation of the scores from PWB, FWB and AnS. The FACT-An Total TOI score range was 0-136. A higher score indicated better QoL.
Time frame: Baseline, weeks 12 to 28 and 36 to 52
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Trial Outcome Index (TOI) Score | Change from BL to weeks 12-28 | 6.798 Units on a scale | Standard Deviation 17.83 |
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Trial Outcome Index (TOI) Score | Change from BL to weeks 36-52 | 5.602 Units on a scale | Standard Deviation 19.302 |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Trial Outcome Index (TOI) Score | Change from BL to weeks 12-28 | 6.876 Units on a scale | Standard Deviation 16.96 |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Trial Outcome Index (TOI) Score | Change from BL to weeks 36-52 | 5.595 Units on a scale | Standard Deviation 19.922 |
Secondary
Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in Work Productivity and Activity Impairment-Anemic Symptoms (WPAI:ANS) Score: Percent Work Time Missed
WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to anaemic symptoms; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the anaemic symptoms on productivity while working; Q6=Impact of the anaemic symptoms on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicated greater activity impairment. Multiply scores by 100 to express in percentages. Percent work time missed due to problem: Q2/(Q2+Q4).
Time frame: Baseline, weeks 12 to 28 and 36 to 52
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in Work Productivity and Activity Impairment-Anemic Symptoms (WPAI:ANS) Score: Percent Work Time Missed | Change from BL to average in weeks 12-28 | -3.793 Percent work time | Standard Deviation 32.987 |
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in Work Productivity and Activity Impairment-Anemic Symptoms (WPAI:ANS) Score: Percent Work Time Missed | Change from BL to average in weeks 36-52 | -0.078 Percent work time | Standard Deviation 37.047 |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in Work Productivity and Activity Impairment-Anemic Symptoms (WPAI:ANS) Score: Percent Work Time Missed | Change from BL to average in weeks 12-28 | 0.842 Percent work time | Standard Deviation 21 |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in Work Productivity and Activity Impairment-Anemic Symptoms (WPAI:ANS) Score: Percent Work Time Missed | Change from BL to average in weeks 36-52 | 0.216 Percent work time | Standard Deviation 23.483 |
Secondary
Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Activity Impairment
WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to anaemic symptoms; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the anaemic symptoms on productivity while working; Q6=Impact of the anaemic symptoms on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicated greater activity impairment. Percent activity impairment due to problem: Q6/10.
Time frame: Baseline, weeks 12 to 28 and 36 to 52
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Activity Impairment | Change from BL to weeks 12-28 | -9.581 Percent impairment | Standard Deviation 27.367 |
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Activity Impairment | Change from BL to weeks 36-52 | -9.365 Percent impairment | Standard Deviation 28.956 |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Activity Impairment | Change from BL to weeks 12-28 | -9.34 Percent impairment | Standard Deviation 27.09 |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Activity Impairment | Change from BL to weeks 36-52 | -8.17 Percent impairment | Standard Deviation 27.486 |
Secondary
Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Impairment While Working
WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to anaemic symptoms; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the anaemic symptoms on productivity while working; Q6=Impact of the anaemic symptoms on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicated greater activity impairment. Percent impairment while working due to problem: Q5/10.
Time frame: Baseline, weeks 12 to 28 and 36 to 52
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Impairment While Working | Change from BL to weeks 36-52 | -7.879 Percent impairment | Standard Deviation 25.872 |
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Impairment While Working | Change from BL to weeks 12-28 | -6.618 Percent impairment | Standard Deviation 22.419 |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Impairment While Working | Change from BL to weeks 36-52 | 1.083 Percent impairment | Standard Deviation 23.102 |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Impairment While Working | Change from BL to weeks 12-28 | -2.433 Percent impairment | Standard Deviation 28.598 |
Secondary
Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Overall Work Impairment
WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to anaemic symptoms; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the anaemic symptoms on productivity while working; Q6=Impact of the anaemic symptoms on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicated greater activity impairment. Percent overall work impairment due to problem: Q2/(Q2+Q4)+\[(1-(Q2/(Q2+Q4))x(Q5/10)\].
Time frame: Baseline, weeks 12 to 28 and 36 to 52
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Overall Work Impairment | Change from BL to weeks 12-28 | -6.112 Percent impairment | Standard Deviation 23.21 |
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Overall Work Impairment | Change From BL to weeks 36-52 | 2.817 Percent impairment | Standard Deviation 30.432 |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Overall Work Impairment | Change from BL to weeks 12-28 | -1.217 Percent impairment | Standard Deviation 20.743 |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Overall Work Impairment | Change From BL to weeks 36-52 | 0.197 Percent impairment | Standard Deviation 23.431 |
Secondary
Change From Baseline to the Average Value of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score
Baseline assessment was defined as the value on day 1. The EQ-5D-5L is a self-reported questionnaire, used as a measure of respondents' health related quality of life (HRQoL) and utility values. The EQ-5D consists of the descriptive system and the VAS. The EQ-5D descriptive system comprises 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, extreme problems. The VAS records the respondent's self rated health status on a graduated (0-100) scale, where the endpoints are labeled 'best imaginable health state' and 'worst imaginable health state' with higher scores for higher HRQoL.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From Baseline to the Average Value of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score | 5.137 Units on a scale |
| Darbepoetin Alfa | Change From Baseline to the Average Value of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score | 4.353 Units on a scale |
Comparison: The model includes treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline EQ-5D 5L VAS, baseline Hb, baseline eGFR as continuous covariates.p-value: 0.49795% CI: [-1.481, 3.049]Mixed Models Analysis
Secondary
Change From Baseline to Weeks 8, 28, 52 and 104 in ApoB/ApoA1 Ratio
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time frame: Baseline and weeks 8, 28, 52, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in ApoB/ApoA1 Ratio | Change from BL to week 52 | -0.025 Ratio | Standard Deviation 0.254 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in ApoB/ApoA1 Ratio | Change from BL to week 8 | -0.031 Ratio | Standard Deviation 0.185 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in ApoB/ApoA1 Ratio | Change from BL to week 104 | -0.044 Ratio | Standard Deviation 0.238 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in ApoB/ApoA1 Ratio | Change from BL to week 28 | -0.026 Ratio | Standard Deviation 0.208 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in ApoB/ApoA1 Ratio | Change from BL to week 104 | -0.009 Ratio | Standard Deviation 0.218 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in ApoB/ApoA1 Ratio | Change from BL to week 28 | -0.034 Ratio | Standard Deviation 0.159 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in ApoB/ApoA1 Ratio | Change from BL to week 52 | -0.038 Ratio | Standard Deviation 0.191 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in ApoB/ApoA1 Ratio | Change from BL to week 8 | -0.019 Ratio | Standard Deviation 0.13 |
Secondary
Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins A1 (ApoA1)
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time frame: Baseline and weeks 8, 28, 52, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins A1 (ApoA1) | Change from BL to week 8 | -0.184 Grams per liter (g/L) | Standard Deviation 0.222 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins A1 (ApoA1) | Change from BL to week 28 | -0.104 Grams per liter (g/L) | Standard Deviation 0.258 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins A1 (ApoA1) | Change from BL to week 104 | -0.116 Grams per liter (g/L) | Standard Deviation 0.311 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins A1 (ApoA1) | Change from BL to week 52 | -0.12 Grams per liter (g/L) | Standard Deviation 0.254 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins A1 (ApoA1) | Change from BL to week 104 | -0.018 Grams per liter (g/L) | Standard Deviation 0.242 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins A1 (ApoA1) | Change from BL to week 28 | 0.055 Grams per liter (g/L) | Standard Deviation 0.217 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins A1 (ApoA1) | Change from BL to week 52 | 0.027 Grams per liter (g/L) | Standard Deviation 0.229 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins A1 (ApoA1) | Change from BL to week 8 | 0.026 Grams per liter (g/L) | Standard Deviation 0.204 |
Secondary
Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins B (ApoB)
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time frame: Baseline and weeks 8, 28, 52, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins B (ApoB) | Change from BL to week 52 | -10.74 Milligrams per deciliter (mg/dL) | Standard Deviation 25.155 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins B (ApoB) | Change from BL to week 8 | -16.5 Milligrams per deciliter (mg/dL) | Standard Deviation 19.581 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins B (ApoB) | Change from BL to week 104 | -13.561 Milligrams per deciliter (mg/dL) | Standard Deviation 25.461 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins B (ApoB) | Change from BL to week 28 | -10.659 Milligrams per deciliter (mg/dL) | Standard Deviation 23.644 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins B (ApoB) | Change from BL to week 104 | -2.038 Milligrams per deciliter (mg/dL) | Standard Deviation 25.857 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins B (ApoB) | Change from BL to week 28 | 0.091 Milligrams per deciliter (mg/dL) | Standard Deviation 19.672 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins B (ApoB) | Change from BL to week 52 | -3.539 Milligrams per deciliter (mg/dL) | Standard Deviation 23.811 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins B (ApoB) | Change from BL to week 8 | -0.71 Milligrams per deciliter (mg/dL) | Standard Deviation 17.791 |
Secondary
Change From Baseline to Weeks 8, 28, 52 and 104 in LDL-C/High-Density Lipoprotein Cholesterol (HDL-C) Ratio
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time frame: Baseline and weeks 8, 28, 52, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in LDL-C/High-Density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 8 | -0.209 Ratio | Standard Deviation 0.665 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in LDL-C/High-Density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 28 | 0.016 Ratio | Standard Deviation 0.893 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in LDL-C/High-Density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 52 | 0.014 Ratio | Standard Deviation 1.095 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in LDL-C/High-Density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 104 | -0.069 Ratio | Standard Deviation 1.579 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in LDL-C/High-Density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 104 | 0.012 Ratio | Standard Deviation 1.06 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in LDL-C/High-Density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 8 | -0.049 Ratio | Standard Deviation 0.629 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in LDL-C/High-Density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 52 | -0.065 Ratio | Standard Deviation 0.871 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in LDL-C/High-Density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 28 | 0.053 Ratio | Standard Deviation 0.747 |
Secondary
Change From Baseline to Weeks 8, 28, 52 and 104 in Non-HDL Cholesterol
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time frame: Baseline and weeks 8, 28, 52, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Non-HDL Cholesterol | Change from BL to week 52 | -0.383 mmoL/L | Standard Deviation 1.19 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Non-HDL Cholesterol | Change from BL to week 28 | -0.392 mmoL/L | Standard Deviation 1.098 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Non-HDL Cholesterol | Change from BL to week 104 | -0.562 mmoL/L | Standard Deviation 1.162 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Non-HDL Cholesterol | Change from BL to week 8 | -0.729 mmoL/L | Standard Deviation 0.9 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Non-HDL Cholesterol | Change from BL to week 104 | -0.15 mmoL/L | Standard Deviation 1.151 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Non-HDL Cholesterol | Change from BL to week 28 | 0.02 mmoL/L | Standard Deviation 0.911 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Non-HDL Cholesterol | Change from BL to week 52 | -0.114 mmoL/L | Standard Deviation 1.062 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Non-HDL Cholesterol | Change from BL to week 8 | -0.045 mmoL/L | Standard Deviation 0.787 |
Secondary
Change From Baseline to Weeks 8, 28, 52 and 104 in Total Cholesterol
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time frame: Baseline and weeks 8, 28, 52, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Total Cholesterol | Change from BL to week 8 | -0.92 mmol/L | Standard Deviation 0.98 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Total Cholesterol | Change from BL to week 28 | -0.531 mmol/L | Standard Deviation 1.153 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Total Cholesterol | Change from BL to week 52 | -0.524 mmol/L | Standard Deviation 1.232 |
| Roxadustat | Change From Baseline to Weeks 8, 28, 52 and 104 in Total Cholesterol | Change from BL to week 104 | -0.695 mmol/L | Standard Deviation 1.284 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Total Cholesterol | Change from BL to week 104 | -0.197 mmol/L | Standard Deviation 1.171 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Total Cholesterol | Change from BL to week 8 | -0.046 mmol/L | Standard Deviation 0.836 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Total Cholesterol | Change from BL to week 52 | -0.111 mmol/L | Standard Deviation 1.097 |
| Darbepoetin Alfa | Change From Baseline to Weeks 8, 28, 52 and 104 in Total Cholesterol | Change from BL to week 28 | 0.016 mmol/L | Standard Deviation 0.953 |
Secondary
Hb Level Averaged Over Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 Without Rescue Therapy
Baseline Hb was defined as the mean of all available central laboratory Hb values collected before or including the date of first study drug intake (predose).
Time frame: Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Roxadustat | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 Without Rescue Therapy | Weeks 28-36 | 11.403 g/dL |
| Roxadustat | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 Without Rescue Therapy | Weeks 44-52 | 11.185 g/dL |
| Roxadustat | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 Without Rescue Therapy | Weeks 72-80 | 11.225 g/dL |
| Roxadustat | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 Without Rescue Therapy | Weeks 96-104 | 11.102 g/dL |
| Darbepoetin Alfa | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 Without Rescue Therapy | Weeks 96-104 | 11.078 g/dL |
| Darbepoetin Alfa | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 Without Rescue Therapy | Weeks 28-36 | 11.351 g/dL |
| Darbepoetin Alfa | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 Without Rescue Therapy | Weeks 72-80 | 11.217 g/dL |
| Darbepoetin Alfa | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 Without Rescue Therapy | Weeks 44-52 | 11.188 g/dL |
Comparison: Weeks 28-36 - The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline estimated glomerular filtration rate and baseline Hb by visit as continuous covariates.p-value: 0.47895% CI: [-0.091, 0.194]Mixed Models Analysis
Comparison: Weeks 44-52 - The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline estimated glomerular filtration rate and baseline Hb by visit as continuous covariates.p-value: 0.96995% CI: [-0.149, 0.143]Mixed Models Analysis
Comparison: Weeks 72-80 - The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline estimated glomerular filtration rate and baseline Hb by visit as continuous covariates.p-value: 0.9195% CI: [-0.14, 0.157]Mixed Models Analysis
Comparison: Weeks 96-104 - The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline estimated glomerular filtration rate and baseline Hb by visit as continuous covariates.p-value: 0.77595% CI: [-0.14, 0.188]Mixed Models Analysis
Secondary
Mean Monthly Intravenous Iron Per Participant During Weeks 37 to 52 and 53 to 104
Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg.
Time frame: Weeks 37 to 52 and 53 to 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Mean Monthly Intravenous Iron Per Participant During Weeks 37 to 52 and 53 to 104 | Weeks 37 to 52 | 11.028 mg per month | Standard Deviation 64.282 |
| Roxadustat | Mean Monthly Intravenous Iron Per Participant During Weeks 37 to 52 and 53 to 104 | Weeks 53 to 104 | 18.702 mg per month | Standard Deviation 68.074 |
| Darbepoetin Alfa | Mean Monthly Intravenous Iron Per Participant During Weeks 37 to 52 and 53 to 104 | Weeks 37 to 52 | 13.208 mg per month | Standard Deviation 46.408 |
| Darbepoetin Alfa | Mean Monthly Intravenous Iron Per Participant During Weeks 37 to 52 and 53 to 104 | Weeks 53 to 104 | 31.315 mg per month | Standard Deviation 95.306 |
Secondary
Number of Days of Hospitalization Per Year
The number of days of hospitalization per year was calculated as the sum of the durations of all hospitalizations in days (minimum \[date of discharge, end of efficacy of emergent period\] - date of admission + 1) / (duration of efficacy emergent period in days / 365.25). The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period).
Time frame: Baseline to EOT (up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Number of Days of Hospitalization Per Year | 12.6 Days per year | Standard Deviation 22 |
| Darbepoetin Alfa | Number of Days of Hospitalization Per Year | 11.3 Days per year | Standard Deviation 27.7 |
Secondary
Number of Hospitalizations
The number of hospitalizations per participant were calculated during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period).
Time frame: Baseline to EOT (up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Number of Hospitalizations | 1.5 Hospitalizations | Standard Deviation 2.4 |
| Darbepoetin Alfa | Number of Hospitalizations | 1.4 Hospitalizations | Standard Deviation 2.3 |
Secondary
Number of Participants Who Had Achieved Antihypertensive Treatment Goal
Achieved antihypertensive treatment goal was defined as SBP \< 130 mmHg and DBP \< 80 mmHg over an evaluation period defined as the average of available values in weeks 12 to 28 and 36 to 52.
Time frame: Weeks 12 to 28 and 36 to 52
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roxadustat | Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Weeks 12-28: Yes | 76 Participants |
| Roxadustat | Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Weeks 12-28: No | 228 Participants |
| Roxadustat | Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Weeks 36-52: Yes | 80 Participants |
| Roxadustat | Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Week 12-28: Missing | 18 Participants |
| Roxadustat | Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Weeks 36-52: No | 196 Participants |
| Roxadustat | Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Weeks 36-52: Missing | 46 Participants |
| Darbepoetin Alfa | Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Weeks 36-52: No | 193 Participants |
| Darbepoetin Alfa | Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Weeks 12-28: Yes | 64 Participants |
| Darbepoetin Alfa | Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Weeks 36-52: Yes | 64 Participants |
| Darbepoetin Alfa | Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Week 12-28: Missing | 16 Participants |
| Darbepoetin Alfa | Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Weeks 36-52: Missing | 35 Participants |
| Darbepoetin Alfa | Number of Participants Who Had Achieved Antihypertensive Treatment Goal | Weeks 12-28: No | 212 Participants |
Secondary
Number of Participants Who Received Rescue Therapy (Composite of RBC Transfusions (All Participants) and Darbepoetin Alfa Use (Roxadustat Treated Participants Only)
Rescue therapy for participants in the roxadustat group included RBC transfusion or ESA therapy and for participants in the darbepoetin alfa group included RBC transfusion only. Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who have experienced more than one use of rescue therapy (i.e. RBC and ESA), only their first event was used.
Time frame: Baseline to EOT (up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Roxadustat | Number of Participants Who Received Rescue Therapy (Composite of RBC Transfusions (All Participants) and Darbepoetin Alfa Use (Roxadustat Treated Participants Only) | 46 Participants |
| Darbepoetin Alfa | Number of Participants Who Received Rescue Therapy (Composite of RBC Transfusions (All Participants) and Darbepoetin Alfa Use (Roxadustat Treated Participants Only) | 28 Participants |
Secondary
Number of Participants With End Stage Renal Disease (ESRD)
Occurrence of end stage renal disease during the study (i.e from day 1 up to the end of study) was defined as at least one of the following: underwent \>30 days dialysis therapy, received kidney transplant, planned kidney transplant, physician recommended renal replacement therapy and participant refused therapy, began dialysis and died \< 30 days later.
Time frame: Baseline up to EOS (up to week 108)
Population: The analysis population was the FAS.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Roxadustat | Number of Participants With End Stage Renal Disease (ESRD) | 110 Participants |
| Darbepoetin Alfa | Number of Participants With End Stage Renal Disease (ESRD) | 107 Participants |
Secondary
Number of Participants With Mean LDL Cholesterol < 100 mg/dL
Missing category for fasting only includes non-fasting participants and the participants with missing values.
Time frame: Weeks 12 to 28 and 36 to 52
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 36-52: No (Regardless Fasting Status) | 26 Participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12-28: No (Fasting only) | 11 Participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12-28: No (Regardless Fasting Status) | 20 Participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12-28: Missing (Fasting only) | 76 Participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 36-52: Missing (Fasting only) | 84 Participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12-28: Missing (Regardless Fasting Status) | 10 Participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 36-52: Missing (Regardless Fasting Status) | 22 Participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 36-52: Yes (Regardless Fasting Status) | 129 Participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 36-52: Yes (Fasting only) | 78 Participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12-28: Yes (Fasting only) | 90 Participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 36-52: No (Fasting only) | 15 Participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12-28: Yes (Regardless Fasting Status) | 147 Participants |
| Darbepoetin Alfa | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 36-52: No (Fasting only) | 22 Participants |
| Darbepoetin Alfa | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 36-52: Yes (Regardless Fasting Status) | 104 Participants |
| Darbepoetin Alfa | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 36-52: Missing (Fasting only) | 73 Participants |
| Darbepoetin Alfa | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12-28: Yes (Regardless Fasting Status) | 111 Participants |
| Darbepoetin Alfa | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12-28: No (Regardless Fasting Status) | 33 Participants |
| Darbepoetin Alfa | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12-28: Missing (Regardless Fasting Status) | 8 Participants |
| Darbepoetin Alfa | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12-28: Yes (Fasting only) | 69 Participants |
| Darbepoetin Alfa | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12-28: No (Fasting only) | 18 Participants |
| Darbepoetin Alfa | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 12-28: Missing (Fasting only) | 65 Participants |
| Darbepoetin Alfa | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 36-52: No (Regardless Fasting Status) | 31 Participants |
| Darbepoetin Alfa | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 36-52: Missing (Regardless Fasting Status) | 17 Participants |
| Darbepoetin Alfa | Number of Participants With Mean LDL Cholesterol < 100 mg/dL | Weeks 36-52: Yes (Fasting only) | 57 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An AE was defined as any untoward medical occurrence in a participant who was given the study drug or who had undergone study procedures and did not necessarily have a causal relationship with this treatment. All AEs collected during the safety emergent period were counted as TEAE. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the end of treatment taking into account the different dosing frequencies of the study treatments. Based on national cancer institute common terminology criteria (NCI-CTCAE), AEs were graded as grade 1=mild, grade 2=moderate, grade 3 =severe or medically significant, grade 4 =life threatening, grade 5 =death related to AE. All reported deaths after the first study drug administration and up to 28 days after the analysis date of last dose were based on last dosing frequency.
Time frame: From first dose of study drug up to end of study (up to week 108)
Population: The analysis population was the safety analysis set included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roxadustat | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE | 296 Participants |
| Roxadustat | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Drug-Related TEAE | 78 Participants |
| Roxadustat | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Serious TEAE | 209 Participants |
| Roxadustat | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Drug-Related TEAE Leading to Withdraw of Treatment | 7 Participants |
| Roxadustat | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE NCI CTC Grades 3 or Higher | 181 Participants |
| Roxadustat | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Drug-Related Serious TEAE | 18 Participants |
| Roxadustat | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 34 Participants |
| Roxadustat | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Drug-Related TEAE Leading to Death | 2 Participants |
| Roxadustat | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE Leading to Withdrawal of Treatment | 25 Participants |
| Darbepoetin Alfa | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE | 271 Participants |
| Darbepoetin Alfa | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Serious TEAE | 181 Participants |
| Darbepoetin Alfa | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Drug-Related TEAE | 66 Participants |
| Darbepoetin Alfa | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 34 Participants |
| Darbepoetin Alfa | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE Leading to Withdrawal of Treatment | 11 Participants |
| Darbepoetin Alfa | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Drug-Related Serious TEAE | 9 Participants |
| Darbepoetin Alfa | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Drug-Related TEAE Leading to Withdraw of Treatment | 1 Participants |
| Darbepoetin Alfa | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Drug-Related TEAE Leading to Death | 0 Participants |
| Darbepoetin Alfa | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE NCI CTC Grades 3 or Higher | 164 Participants |
Secondary
Number of Particpants Who Received RBC Transfusions
Participants who received RBC transfusions during the efficacy emergent period were reported. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period).
Time frame: Baseline to EOT (up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Roxadustat | Number of Particpants Who Received RBC Transfusions | 38 Participants |
| Darbepoetin Alfa | Number of Particpants Who Received RBC Transfusions | 28 Participants |
Secondary
Number of RBC Packs
The number of RBC packs were calculated as the sum of units transfused during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT visit or last non-missing Hb assessment (for participants who died during the treatment period). Participants with no medication records of RBC have their number of RBC packs set to 0.
Time frame: Baseline to EOT (up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Number of RBC Packs | 0.4 RBC packs | Standard Deviation 1.2 |
| Darbepoetin Alfa | Number of RBC Packs | 0.4 RBC packs | Standard Deviation 1.98 |
Secondary
Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy
Percentage for each participant was calculated from the number of Hb values within 10.0-12.0 g/dL / total number of Hb values\*100 in weeks 28 to 36, 44 to 52 and 96 to 104 without use of rescue therapy within 6 weeks prior to and during the 8 week evaluation period.
Time frame: Weeks 28 to 36, 44 to 52 and 96 to 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 28-36, Within 10-12 | 67.896 Percentage of Hb values | Standard Deviation 33.499 |
| Roxadustat | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 72-80, >= 10 | 91.494 Percentage of Hb values | Standard Deviation 20.923 |
| Roxadustat | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 44-52, Within 10-12 | 74.104 Percentage of Hb values | Standard Deviation 32.119 |
| Roxadustat | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 72-80, Within 10-12 | 69.71 Percentage of Hb values | Standard Deviation 32.444 |
| Roxadustat | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 44-52, >= 10 | 90.921 Percentage of Hb values | Standard Deviation 23.123 |
| Roxadustat | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 96-104, >= 10 | 90.436 Percentage of Hb values | Standard Deviation 22.725 |
| Roxadustat | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 96-104, Within 10-12 | 72.393 Percentage of Hb values | Standard Deviation 33.277 |
| Roxadustat | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 28-36, >= 10 | 93.078 Percentage of Hb values | Standard Deviation 20.671 |
| Darbepoetin Alfa | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 96-104, Within 10-12 | 68.629 Percentage of Hb values | Standard Deviation 35.352 |
| Darbepoetin Alfa | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 28-36, >= 10 | 92.481 Percentage of Hb values | Standard Deviation 19.876 |
| Darbepoetin Alfa | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 44-52, >= 10 | 89.416 Percentage of Hb values | Standard Deviation 24.833 |
| Darbepoetin Alfa | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 96-104, >= 10 | 87.777 Percentage of Hb values | Standard Deviation 27.03 |
| Darbepoetin Alfa | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 28-36, Within 10-12 | 69.217 Percentage of Hb values | Standard Deviation 34.171 |
| Darbepoetin Alfa | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 44-52, Within 10-12 | 68.931 Percentage of Hb values | Standard Deviation 35.367 |
| Darbepoetin Alfa | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 72-80, >= 10 | 90.343 Percentage of Hb values | Standard Deviation 24.364 |
| Darbepoetin Alfa | Percentage of Hb Values >=10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 72-80, Within 10-12 | 67.861 Percentage of Hb values | Standard Deviation 37.024 |
Secondary
Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC)
The PGIC is a patient-rated instrument that measured change in participant's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), when compared to the start of treatment. The percentage of participants presented included very much improved, much improved and minimally improved.
Time frame: Weeks 8, 12, 28, 52, 76, 104, last assessment (week 108)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 52 | 79.3 Percentage of Participants |
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 28 | 83 Percentage of Participants |
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Last Assessment | 70.6 Percentage of Participants |
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 76 | 73 Percentage of Participants |
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 12 | 83.7 Percentage of Participants |
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 104 | 71.8 Percentage of Participants |
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 8 | 76.1 Percentage of Participants |
| Darbepoetin Alfa | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 104 | 76 Percentage of Participants |
| Darbepoetin Alfa | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 8 | 79.4 Percentage of Participants |
| Darbepoetin Alfa | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 28 | 81 Percentage of Participants |
| Darbepoetin Alfa | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Last Assessment | 71.4 Percentage of Participants |
| Darbepoetin Alfa | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 12 | 83.6 Percentage of Participants |
| Darbepoetin Alfa | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 52 | 79.8 Percentage of Participants |
| Darbepoetin Alfa | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 76 | 74.9 Percentage of Participants |
Secondary
Percentage of Participants With Oral Iron Use Only
Percentage of participants with oral iron use only were calculated based on total number of participants within the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period).
Time frame: Day 1 to week 36, weeks 37 to 52, weeks 53 to 104, efficacy emergent period (up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Percentage of Participants With Oral Iron Use Only | During week 37 to 52 | 55.6 Percentage of Participants |
| Roxadustat | Percentage of Participants With Oral Iron Use Only | During efficacy emergent period | 50.6 Percentage of Participants |
| Roxadustat | Percentage of Participants With Oral Iron Use Only | During week 53 to 104 | 53.1 Percentage of Participants |
| Roxadustat | Percentage of Participants With Oral Iron Use Only | During day 1 to week 36 | 55.3 Percentage of Participants |
| Darbepoetin Alfa | Percentage of Participants With Oral Iron Use Only | During week 53 to 104 | 50.6 Percentage of Participants |
| Darbepoetin Alfa | Percentage of Participants With Oral Iron Use Only | During day 1 to week 36 | 55.1 Percentage of Participants |
| Darbepoetin Alfa | Percentage of Participants With Oral Iron Use Only | During week 37 to 52 | 55.4 Percentage of Participants |
| Darbepoetin Alfa | Percentage of Participants With Oral Iron Use Only | During efficacy emergent period | 52.7 Percentage of Participants |
Secondary
Rate of Progression of Chronic Kidney Disease Measured by eGFR Slope Over Time
Annualized eGFR slope over time was estimated by a random slopes and intercepts model using all available eGFR values (one baseline and all post-treatment values up to EOT period or start of dialysis adjusted on baseline Hb, region, CV history at baseline and the interaction terms (baseline eGFR by timepoint and baseline Hb by timepoint). All assessments collected after initiation of dialysis (acute or chronic) were excluded from the analysis. Baseline assessment was the assessment from day 1 visit. If this value was missing, the value from screening visit was used.
Time frame: Baseline up to EOS (up to week 108)
Population: The analysis population was the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Rate of Progression of Chronic Kidney Disease Measured by eGFR Slope Over Time | -2.95 ml/min per 1.73 m^2 |
| Darbepoetin Alfa | Rate of Progression of Chronic Kidney Disease Measured by eGFR Slope Over Time | -2.89 ml/min per 1.73 m^2 |
p-value: 0.90295% CI: [-0.93, 0.82]Mixed Models Analysis
Secondary
Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant
For participants who had at least 40% decrease in eGFR from baseline, chronic dialysis or renal transplant during the safety emergent period, only their first occurrence was used. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the end of treatment taking into account the different dosing frequencies of the study treatments. Data reported was analyzed by kaplan-meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time frame: Year 0.5, 1, 1.5 and 2
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Year 2 | 55.7 Percentage of participants |
| Roxadustat | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Year 1 | 34.5 Percentage of participants |
| Roxadustat | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Year 0.5 | 15.4 Percentage of participants |
| Roxadustat | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Year 1.5 | 47.2 Percentage of participants |
| Darbepoetin Alfa | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Year 1.5 | 50.2 Percentage of participants |
| Darbepoetin Alfa | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Year 1 | 35.5 Percentage of participants |
| Darbepoetin Alfa | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Year 2 | 59.3 Percentage of participants |
| Darbepoetin Alfa | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Year 0.5 | 13 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates. Superiority was declared if the upper bound of the 95% CI was below 1.0.p-value: 0.56895% CI: [0.75, 1.17]Regression, Cox
Secondary
Time to Chronic Dialysis or Renal Transplant or Death
For participants who had chronic dialysis or renal transplant or died, only their first occurrence during the safety emergent period was used. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the end of treatment taking into account the different dosing frequencies of the study treatments. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure.
Time frame: Year 0.5, 1, 1.5 and 2
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to Chronic Dialysis or Renal Transplant or Death | Year 0.5 | 12.7 Percentage of participants |
| Roxadustat | Time to Chronic Dialysis or Renal Transplant or Death | Year 1 | 27.1 Percentage of participants |
| Roxadustat | Time to Chronic Dialysis or Renal Transplant or Death | Year 2 | 42.9 Percentage of participants |
| Roxadustat | Time to Chronic Dialysis or Renal Transplant or Death | Year 1.5 | 37.1 Percentage of participants |
| Darbepoetin Alfa | Time to Chronic Dialysis or Renal Transplant or Death | Year 1.5 | 37.7 Percentage of participants |
| Darbepoetin Alfa | Time to Chronic Dialysis or Renal Transplant or Death | Year 0.5 | 9.2 Percentage of participants |
| Darbepoetin Alfa | Time to Chronic Dialysis or Renal Transplant or Death | Year 2 | 45.6 Percentage of participants |
| Darbepoetin Alfa | Time to Chronic Dialysis or Renal Transplant or Death | Year 1 | 26.2 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates. Superiority was declared if the upper bound of the 95% CI was below 1.0.p-value: 0.94895% CI: [0.77, 1.27]Regression, Cox
Secondary
Time to Chronic Kidney Disease Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death)
Chronic kidney disease progression was defined as date of occurrence of chronic dialysis or date of renal transplant or doubled serum creatinine or date of death, whichever came first. For participants who had chronic dialysis or renal transplant or died, only their first occurrence during the safety emergent period was used. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the end of treatment taking into account the different dosing frequencies of the study treatments. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure.
Time frame: Year 0.5, 1, 1.5 and 2
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to Chronic Kidney Disease Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Year 0.5 | 14 Percentage of participants |
| Roxadustat | Time to Chronic Kidney Disease Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Year 1 | 30.9 Percentage of participants |
| Roxadustat | Time to Chronic Kidney Disease Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Year 1.5 | 42.1 Percentage of participants |
| Roxadustat | Time to Chronic Kidney Disease Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Year 2 | 49.9 Percentage of participants |
| Darbepoetin Alfa | Time to Chronic Kidney Disease Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Year 2 | 51 Percentage of participants |
| Darbepoetin Alfa | Time to Chronic Kidney Disease Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Year 0.5 | 10.2 Percentage of participants |
| Darbepoetin Alfa | Time to Chronic Kidney Disease Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Year 1.5 | 42.6 Percentage of participants |
| Darbepoetin Alfa | Time to Chronic Kidney Disease Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Year 1 | 29.5 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates. Superiority was declared if the upper bound of the 95% CI was below 1.0.p-value: 0.93995% CI: [0.79, 1.25]Regression, Cox
Secondary
Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline
For participants who had doubled their serum creatinine or had chronic dialysis or renal transplant more than once, only their first occurrence during safety emergent period was used. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the end of treatment taking into account the different dosing frequencies of the study treatments. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure.
Time frame: Year 0.5, 1, 1.5 and 2
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Year 1 | 27.4 Percentage of Participants |
| Roxadustat | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Year 1.5 | 38.2 Percentage of Participants |
| Roxadustat | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Year 2 | 46.5 Percentage of Participants |
| Roxadustat | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Year 0.5 | 12.9 Percentage of Participants |
| Darbepoetin Alfa | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Year 0.5 | 8.6 Percentage of Participants |
| Darbepoetin Alfa | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Year 1 | 27.2 Percentage of Participants |
| Darbepoetin Alfa | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Year 2 | 45.4 Percentage of Participants |
| Darbepoetin Alfa | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Year 1.5 | 38.8 Percentage of Participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates. Superiority was declared if the upper bound of the 95% CI was below 1.0.p-value: 0.9695% CI: [0.79, 1.29]Regression, Cox
Secondary
Time to First Hb Rate of Rise > 2 g/dL Within 4 Weeks
Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who had experienced more than one event, only their first event was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure.
Time frame: Year 0.5, 1, 1.5 and 2
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Hb Rate of Rise > 2 g/dL Within 4 Weeks | Year 1 | 48.8 Percentage of participants |
| Roxadustat | Time to First Hb Rate of Rise > 2 g/dL Within 4 Weeks | Year 0.5 | 45.5 Percentage of participants |
| Roxadustat | Time to First Hb Rate of Rise > 2 g/dL Within 4 Weeks | Year 1.5 | 53.4 Percentage of participants |
| Roxadustat | Time to First Hb Rate of Rise > 2 g/dL Within 4 Weeks | Year 2 | 55.3 Percentage of participants |
| Darbepoetin Alfa | Time to First Hb Rate of Rise > 2 g/dL Within 4 Weeks | Year 2 | 37.8 Percentage of participants |
| Darbepoetin Alfa | Time to First Hb Rate of Rise > 2 g/dL Within 4 Weeks | Year 0.5 | 28.9 Percentage of participants |
| Darbepoetin Alfa | Time to First Hb Rate of Rise > 2 g/dL Within 4 Weeks | Year 1.5 | 35 Percentage of participants |
| Darbepoetin Alfa | Time to First Hb Rate of Rise > 2 g/dL Within 4 Weeks | Year 1 | 30.9 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on CV history and Region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: <0.00195% CI: [1.36, 2.22]Regression, Cox
Secondary
Time to First Hb Response During First 24 Weeks of Treatment Regardless of Administration of Rescue Therapy
Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who had experienced more than one event, only their first event was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion. Percentage of participants were reported in this outcome measure.
Time frame: Weeks 1 to 24
Population: The analysis population was the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Time to First Hb Response During First 24 Weeks of Treatment Regardless of Administration of Rescue Therapy | 88.8 Percentage of Participants |
| Darbepoetin Alfa | Time to First Hb Response During First 24 Weeks of Treatment Regardless of Administration of Rescue Therapy | 77.7 Percentage of Participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on cardiovascular history and region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: <0.00195% CI: [1.38, 1.96]Regression, Cox
Secondary
Time to First Hb Response During First 24 Weeks of Treatment Without Rescue Therapy
Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who had experienced more than one event, only their first event was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion. Percentage of participants were reported in this outcome measure.
Time frame: Weeks 1 to 24
Population: The analysis population was the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Time to First Hb Response During First 24 Weeks of Treatment Without Rescue Therapy | 88.2 Percentage of participants |
| Darbepoetin Alfa | Time to First Hb Response During First 24 Weeks of Treatment Without Rescue Therapy | 77.4 Percentage of participants |
Comparison: Hazard ratio was calculated using stratified Cox Proportional Hazards regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: <0.00195% CI: [1.39, 1.98]Regression, Cox
Secondary
Time to First Hospitalization
Time to first hospitalization in years was defined in years as: (first event date during the efficacy emergent period - analysis date of first dose intake +1)/365.25, and the 'first event date' was defined as 'date of first admission and 'analysis date of first dose intake. Date of end of efficacy emergent period was defined as as the treatment period up to the EOT visit. For participants who have experienced more than one hospitalization, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure.
Time frame: Year 0.5, 1, 1.5 and 2
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Hospitalization | Year 1 | 43.7 Percentage of participants |
| Roxadustat | Time to First Hospitalization | Year 0.5 | 31.7 Percentage of participants |
| Roxadustat | Time to First Hospitalization | Year 2 | 62.3 Percentage of participants |
| Roxadustat | Time to First Hospitalization | Year 1.5 | 55.2 Percentage of participants |
| Darbepoetin Alfa | Time to First Hospitalization | Year 2 | 56.7 Percentage of participants |
| Darbepoetin Alfa | Time to First Hospitalization | Year 0.5 | 21.8 Percentage of participants |
| Darbepoetin Alfa | Time to First Hospitalization | Year 1.5 | 50.2 Percentage of participants |
| Darbepoetin Alfa | Time to First Hospitalization | Year 1 | 40.4 Percentage of participants |
Comparison: Hazard ratio was calculated using stratified Cox Proportional Hazards regression stratifying on CV history and Region and adjusting on Hb and eGFR at baseline as continuous covariates. Superiority was declared if the upper bound of the 95% CI is below 1.0.p-value: 0.07995% CI: [0.98, 1.5]Regression, Cox
Secondary
Time to First Intravenous Iron Use
Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to end of treatment (EOT) Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who had received more than one intravenous iron, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure.
Time frame: Weeks 6, 12, 18, 24, 30 and 36
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Intravenous Iron Use | Week 24 | 4.3 Percentage of participants |
| Roxadustat | Time to First Intravenous Iron Use | Week 36 | 6.7 Percentage of participants |
| Roxadustat | Time to First Intravenous Iron Use | Week 6 | 0 Percentage of participants |
| Roxadustat | Time to First Intravenous Iron Use | Week 12 | 1.3 Percentage of participants |
| Roxadustat | Time to First Intravenous Iron Use | Week 18 | 3.3 Percentage of participants |
| Roxadustat | Time to First Intravenous Iron Use | Week 30 | 5.3 Percentage of participants |
| Darbepoetin Alfa | Time to First Intravenous Iron Use | Week 18 | 9.2 Percentage of participants |
| Darbepoetin Alfa | Time to First Intravenous Iron Use | Week 24 | 10.7 Percentage of participants |
| Darbepoetin Alfa | Time to First Intravenous Iron Use | Week 12 | 6.7 Percentage of participants |
| Darbepoetin Alfa | Time to First Intravenous Iron Use | Week 36 | 13.3 Percentage of participants |
| Darbepoetin Alfa | Time to First Intravenous Iron Use | Week 30 | 12.6 Percentage of participants |
| Darbepoetin Alfa | Time to First Intravenous Iron Use | Week 6 | 2.8 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on cardiovascular history and region and adjusting on Hb and eGFR at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0.p-value: 0.00495% CI: [0.26, 0.78]Regression, Cox
Secondary
Time to First Occurrence of Hypertension During Weeks 1 to 36: Full Analysis Set
Hypertension was defined as either SBP ≥ 170 mmHg and an increase from baseline ≥ 20 mmHg or as DBP ≥ 110 mmHg and an increase from baseline ≥ 15 mmHg. For participants who had experienced more than one event, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion. Percentage of participants were reported in this outcome measure.
Time frame: Weeks 1 to 36
Population: The analysis population was the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Time to First Occurrence of Hypertension During Weeks 1 to 36: Full Analysis Set | 17.4 Percentage of Participants |
| Darbepoetin Alfa | Time to First Occurrence of Hypertension During Weeks 1 to 36: Full Analysis Set | 18.8 Percentage of Participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on cardiovascular history and region and adjusting on Hb and eGFR at baseline as continuous covariates. Superiority was declared if the upper bound of the 95% CI is lower than 1.p-value: 0.45295% CI: [0.6, 1.26]Regression, Cox
Secondary
Time to First Occurrence of Hypertension During Weeks 1 to 36: Per Protocol Set
Hypertension was defined as either SBP ≥ 170 mmHg and an increase from baseline ≥ 20 mmHg or as DBP ≥ 110 mmHg and an increase from baseline ≥ 15 mmHg. For participants who had experienced more than one event, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion. Percentage of participants were reported in this outcome measure.
Time frame: Weeks 1 to 36
Population: The analysis population was the PPS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Time to First Occurrence of Hypertension During Weeks 1 to 36: Per Protocol Set | 17.5 Percentage of Participants |
| Darbepoetin Alfa | Time to First Occurrence of Hypertension During Weeks 1 to 36: Per Protocol Set | 19.4 Percentage of Participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on CV history and Region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: 0.33695% CI: [0.56, 1.22]Regression, Cox
Secondary
Time to First Use of IV Iron Supplementation
Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who had received more than one IV iron, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure.
Time frame: Year 0.5, 1, 1.5 and 2
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Use of IV Iron Supplementation | Year 0.5 | 4.3 Percentage of participants |
| Roxadustat | Time to First Use of IV Iron Supplementation | Year 1.5 | 15.9 Percentage of participants |
| Roxadustat | Time to First Use of IV Iron Supplementation | Year 1 | 10 Percentage of participants |
| Roxadustat | Time to First Use of IV Iron Supplementation | Year 2 | 24.9 Percentage of participants |
| Darbepoetin Alfa | Time to First Use of IV Iron Supplementation | Year 2 | 29.1 Percentage of participants |
| Darbepoetin Alfa | Time to First Use of IV Iron Supplementation | Year 1.5 | 24.2 Percentage of participants |
| Darbepoetin Alfa | Time to First Use of IV Iron Supplementation | Year 0.5 | 11.8 Percentage of participants |
| Darbepoetin Alfa | Time to First Use of IV Iron Supplementation | Year 1 | 19.2 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI is below 1.0.p-value: 0.05295% CI: [0.51, 1]Regression, Cox
Secondary
Time to First Use of RBC Transfusion
Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who had experienced more than one RBC transfusion, only their first event was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure.
Time frame: Year 0.5, 1, 1.5 and 2
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Use of RBC Transfusion | Year 2 | 13.9 Percentage of participants |
| Roxadustat | Time to First Use of RBC Transfusion | Year 1.5 | 10.9 Percentage of participants |
| Roxadustat | Time to First Use of RBC Transfusion | Year 1 | 7.3 Percentage of participants |
| Roxadustat | Time to First Use of RBC Transfusion | Year 0.5 | 3 Percentage of participants |
| Darbepoetin Alfa | Time to First Use of RBC Transfusion | Year 1.5 | 9.4 Percentage of participants |
| Darbepoetin Alfa | Time to First Use of RBC Transfusion | Year 0.5 | 2.1 Percentage of participants |
| Darbepoetin Alfa | Time to First Use of RBC Transfusion | Year 1 | 6.5 Percentage of participants |
| Darbepoetin Alfa | Time to First Use of RBC Transfusion | Year 2 | 11.2 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates. Superiority was declared if the upper bound of the 95% CI is below 1.0.p-value: 0.395% CI: [0.79, 2.11]Regression, Cox
Secondary
Time to First Use of Rescue Therapy
Rescue therapy for participants in the roxadustat group included RBC transfusion or ESA therapy and for participants in the darbepoetin alfa group included RBC transfusion only. Participants were analyzed during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). For participants who have experienced more than one use of rescue therapy (i.e. RBC and ESA), only their first event was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. Percentage of participants were reported in this outcome measure.
Time frame: Year 0.5, 1, 1.5 and 2
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Use of Rescue Therapy | Year 0.5 | 4 Percentage of participants |
| Roxadustat | Time to First Use of Rescue Therapy | Year 1.5 | 13.3 Percentage of participants |
| Roxadustat | Time to First Use of Rescue Therapy | Year 2 | 16.7 Percentage of participants |
| Roxadustat | Time to First Use of Rescue Therapy | Year 1 | 9.3 Percentage of participants |
| Darbepoetin Alfa | Time to First Use of Rescue Therapy | Year 2 | 11.2 Percentage of participants |
| Darbepoetin Alfa | Time to First Use of Rescue Therapy | Year 0.5 | 2.1 Percentage of participants |
| Darbepoetin Alfa | Time to First Use of Rescue Therapy | Year 1 | 6.5 Percentage of participants |
| Darbepoetin Alfa | Time to First Use of Rescue Therapy | Year 1.5 | 9.4 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on CV history and Region and adjusting on Hb and eGFR at baseline as continuous covariates. Superiority was declared if the upper bound of the 95% CI is below 1.0.p-value: 0.05595% CI: [0.99, 2.54]Regression, Cox
Secondary
Volume of RBC Transfused
The volume of blood transfused was calculated as the sum of blood volume transfused during the efficacy emergent period. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). Participants with no medication records of RBC have their volume set to 0.
Time frame: Baseline to EOT (up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Volume of RBC Transfused | 97.0 mL | Standard Deviation 112.2 |
| Darbepoetin Alfa | Volume of RBC Transfused | 334.63 mL | Standard Deviation 508.4 |