A Phase 3 interventional study of Roxadustat and Darbepoetin alfa in Anemia in Chronic Kidney Disease in Non-dialysis Patients, sponsored by Astellas Pharma Europe B.V.. Completed at 125 sites in 26 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-14.
Sponsored by Astellas Pharma Europe B.V. (part of Astellas Pharma Inc) · Phase 3, Interventional, and Treatment
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.
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:
3,090 studies on the registry are indexed under Renal Insufficiency, Chronic; 698 are open to participants now.
This study's enrollment of 616 is above the median of 73 across 2,157 interventional studies indexed under Renal Insufficiency, Chronic.
Browse Renal Insufficiency, Chronic studies →Astellas Pharma Europe B.V. is the lead sponsor of 94 studies on the registry; none are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 4 (80%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Subject has one or more for treatment with darbepoetin alfa:
Subject is positive for any of the following:
Subject will be excluded from participation if any of the following apply:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants received roxadustat orally according to the tiered weight-based approach, with starting dose of 70 mg (milligram) given thrice weekly (TIW) to participants weighing up to 70 kg (kilogram) and 100 mg given TIW to participants weighing more than 70 kg. Dose-titration was performed based upon regular measurement of Hb levels until participants achieved central Hb value of ≥ 11.0 g/dL (gram per deciliter) 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 up to a maximum of 104 weeks.
Drug: Roxadustat
Participants received initial dose of darbepoetin alfa based upon the weight (either 0.45 μg/kg (microgram per kilogram), as a single subcutaneous or intravenous (IV) injection once weekly or 0.75 μg/kg, as a single subcutaneous injection once every 2 weeks) as per European Summary of Product Characteristics (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.
Drug: Darbepoetin alfa
Oral tablet.
Also known as: ASP1517
Subcutaneous or intravenous injection.
Also known as: Aranesp
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
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
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
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)
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)
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)
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
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)
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
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
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
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)
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)
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)
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)
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)
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
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
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)
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
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
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
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)
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.
| Milestone | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Started | 323 | 293 |
| Completed | 250 | 230 |
| Not completed | 73 | 63 |
| Withdrew: Adverse event | 2 | 1 |
| Withdrew: Death | 33 | 34 |
| Withdrew: Lost to follow-up | 3 | 3 |
| Withdrew: Progressive disease | 0 | 1 |
| Withdrew: Withdrawal by subject | 30 | 18 |
| Withdrew: Physician decision | 3 | 3 |
| Withdrew: Miscellaneous | 2 | 3 |
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).
| Percentage of Participants | Roxadustat | 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 | 89.5 | 78.0 |
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).
| g/dL | Roxadustat | 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 | 1.848 ± 1.079 | 1.839 ± 0.973 |
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.
| Millimoles per liter (mmol/L) | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28 | -0.352 ± 0.772 | 0.049 ± 0.705 |
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.
| Percentage of participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Week 6 | 0 (0 to 0) | 2.8 (0.9 to 4.6) |
| Week 12 | 1.3 (0 to 2.5) | 6.7 (3.8 to 9.6) |
| Week 18 | 3.3 (1.3 to 5.2) | 9.2 (5.8 to 12.6) |
| Week 24 | 4.3 (2 to 6.5) | 10.7 (7.1 to 14.3) |
| Week 30 | 5.3 (2.8 to 7.8) | 12.6 (8.7 to 16.5) |
| Week 36 | 6.7 (3.9 to 9.6) | 13.3 (9.3 to 17.3) |
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.
| Units on a scale | Roxadustat | 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 | 0.913 ± 7.182 | 2.062 ± 7.838 |
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.
| Units on a scale | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change From Baseline in SF-36 Vitality (VT) Sub-Score to the Average VT Sub-Score in Weeks 12 to 28 | 4.077 ± 8.657 | 3.881 ± 8.76 |
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).
| Millimeters of mercury (mmHg) | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change From Baseline in Mean Arterial Pressure (MAP) to the Average MAP Value in Weeks 20 to 28: Per Protocol Set | 0.541 ± 8.549 | 0.588 ± 8.779 |
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.
| Percentage of Participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Time to First Occurrence of Hypertension During Weeks 1 to 36: Per Protocol Set | 17.5 | 19.4 |
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.
| mmHg | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change From Baseline in MAP to the Average MAP Value in Weeks 20 to 28: Full Analysis Set | 0.635 ± 8.529 | 0.457 ± 8.741 |
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.
| Percentage of Participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Time to First Occurrence of Hypertension During Weeks 1 to 36: Full Analysis Set | 17.4 | 18.8 |
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).
| g/dL | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change From Baseline in Hb to the Average Hb Value of Weeks 28 to 52 Regardless of Rescue Therapy | 1.718 ± 0.958 | 1.673 ± 0.923 |
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.
| Percentage of Participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Time to First Hb Response During First 24 Weeks of Treatment Regardless of Administration of Rescue Therapy | 88.8 | 77.7 |
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.
| Percentage of participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Time to First Hb Response During First 24 Weeks of Treatment Without Rescue Therapy | 88.2 | 77.4 |
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).
| g/dL | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Weeks 28-36 | 11.403 (11.302 to 11.503) | 11.351 (11.247 to 11.455) |
| Weeks 44-52 | 11.185 (11.082 to 11.289) | 11.188 (11.082 to 11.294) |
| Weeks 72-80 | 11.225 (11.120 to 11.331) | 11.217 (11.110 to 11.324) |
| Weeks 96-104 | 11.102 (10.986 to 11.219) | 11.078 (10.960 to 11.196) |
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).
| g/dL | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Hb Change From BL to week 1 | 0.381 (0.311 to 0.45) | 0.294 (0.221 to 0.368) |
| Hb Change From BL to week 2 | 0.862 (0.782 to 0.941) | 0.584 (0.5 to 0.667) |
| Hb Change From BL to week 4 | 1.508 (1.403 to 1.613) | 1.073 (0.962 to 1.183) |
| Hb Change From BL to week 6 | 1.845 (1.729 to 1.962) | 1.423 (1.3 to 1.546) |
| Hb Change From BL to week 8 | 2.063 (1.94 to 2.185) | 1.682 (1.554 to 1.81) |
| Hb Change From BL to week 10 | 1.941 (1.819 to 2.062) | 1.611 (1.483 to 1.739) |
| Hb Change From BL to week 12 | 2.33 (2.204 to 2.456) | 2.03 (1.897 to 2.162) |
| Hb Change From BL to week 14 | 1.904 (1.781 to 2.027) | 1.745 (1.616 to 1.875) |
| Hb Change From BL to week 16 | 2.177 (2.053 to 2.301) | 1.994 (1.864 to 2.124) |
| Hb Change From BL to week 18 | 1.783 (1.669 to 1.896) | 1.609 (1.49 to 1.729) |
| Hb Change From BL to week 20 | 1.986 (1.869 to 2.103) | 1.9 (1.778 to 2.023) |
| Hb Change From BL to week 22 | 1.584 (1.473 to 1.696) | 1.615 (1.499 to 1.731) |
| Hb Change From BL to week 24 | 1.493 (1.383 to 1.603) | 1.554 (1.438 to 1.669) |
| Hb Change From BL to week 28 | 1.803 (1.688 to 1.919) | 1.869 (1.748 to 1.989) |
| Hb Change From BL to week 32 | 1.687 (1.568 to 1.806) | 1.673 (1.549 to 1.797) |
| Hb Change From BL to Week 36 | 1.913 (1.793 to 2.032) | 1.781 (1.657 to 1.905) |
| Hb Change From BL to week 40 | 1.625 (1.51 to 1.74) | 1.438 (1.32 to 1.556) |
| Hb Change From BL to week 44 | 1.65 (1.527 to 1.773) | 1.628 (1.502 to 1.754) |
| Hb Change From BL to week 48 | 1.459 (1.338 to 1.581) | 1.447 (1.322 to 1.572) |
| Hb Change From BL to week 52 | 1.682 (1.56 to 1.803) | 1.71 (1.585 to 1.835) |
| Hb Change From BL to week 56 | 1.412 (1.292 to 1.533) | 1.444 (1.321 to 1.567) |
| Hb Change From BL to week 60 | 1.735 (1.611 to 1.859) | 1.67 (1.543 to 1.796) |
| Hb Change From BL to week 64 | 1.546 (1.415 to 1.676) | 1.547 (1.414 to 1.681) |
| Hb Change From BL to week 68 | 1.851 (1.726 to 1.976) | 1.747 (1.62 to 1.875) |
| Hb Change From BL to week 72 | 1.615 (1.486 to 1.745) | 1.548 (1.416 to 1.68) |
| Hb Change From BL to week 76 | 1.745 (1.616 to 1.873) | 1.767 (1.636 to 1.898) |
| Hb Change From BL to week 80 | 1.534 (1.408 to 1.661) | 1.579 (1.451 to 1.707) |
| Hb Change From BL to week 84 | 1.723 (1.594 to 1.853) | 1.679 (1.548 to 1.809) |
| Hb Change From BL to week 88 | 1.424 (1.291 to 1.557) | 1.37 (1.236 to 1.504) |
| Hb Change From BL to week 92 | 1.677 (1.541 to 1.812) | 1.643 (1.505 to 1.78) |
| Hb Change From BL to week 96 | 1.429 (1.293 to 1.566) | 1.404 (1.266 to 1.542) |
| Hb Change From BL to week 100 | 1.488 (1.346 to 1.629) | 1.598 (1.454 to 1.742) |
| Hb Change From BL to week 104 | 1.489 (1.339 to 1.64) | 1.452 (1.299 to 1.606) |
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).
| g/dL | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Hb Change From BL to weeks 28-36 | 1.825 (1.723 to 1.926) | 1.799 (1.694 to 1.905) |
| Hb Change From BL to weeks 44-52 | 1.619 (1.513 to 1.724) | 1.62 (1.512 to 1.729) |
| Hb Change From BL to weeks 72-80 | 1.652 (1.545 to 1.759) | 1.649 (1.54 to 1.758) |
| Hb Change From BL to weeks 96-104 | 1.486 (1.363 to 1.608) | 1.502 (1.378 to 1.626) |
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.
| Percentage of Hb values | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Weeks 28-36, >= 10 | 93.078 ± 20.671 | 92.481 ± 19.876 |
| Weeks 28-36, Within 10-12 | 67.896 ± 33.499 | 69.217 ± 34.171 |
| Weeks 44-52, >= 10 | 90.921 ± 23.123 | 89.416 ± 24.833 |
| Weeks 44-52, Within 10-12 | 74.104 ± 32.119 | 68.931 ± 35.367 |
| Weeks 72-80, >= 10 | 91.494 ± 20.923 | 90.343 ± 24.364 |
| Weeks 72-80, Within 10-12 | 69.71 ± 32.444 | 67.861 ± 37.024 |
| Weeks 96-104, >= 10 | 90.436 ± 22.725 | 87.777 ± 27.03 |
| Weeks 96-104, Within 10-12 | 72.393 ± 33.277 | 68.629 ± 35.352 |
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.
| Percentage of participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Year 0.5 | 45.5 (40 to 51) | 28.9 (23.6 to 34.1) |
| Year 1 | 48.8 (43.2 to 54.4) | 30.9 (25.4 to 36.3) |
| Year 1.5 | 53.4 (47.7 to 59.1) | 35 (29.3 to 40.7) |
| Year 2 | 55.3 (49.5 to 61) | 37.8 (31.9 to 43.7) |
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).
| Hospitalizations | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Number of Hospitalizations | 1.5 ± 2.4 | 1.4 ± 2.3 |
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).
| Days per year | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Number of Days of Hospitalization Per Year | 12.6 ± 22 | 11.3 ± 27.7 |
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.
| Percentage of participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Year 0.5 | 31.7 (26.5 to 36.8) | 21.8 (17 to 26.7) |
| Year 1 | 43.7 (38.2 to 49.3) | 40.4 (34.6 to 46.2) |
| Year 1.5 | 55.2 (49.6 to 60.9) | 50.2 (44.2 to 56.1) |
| Year 2 | 62.3 (56.7 to 67.9) | 56.7 (50.7 to 62.7) |
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.
| Percentage of participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Year 0.5 | 3 (1.1 to 4.9) | 2.1 (0.4 to 3.8) |
| Year 1 | 7.3 (4.3 to 10.3) | 6.5 (3.5 to 9.5) |
| Year 1.5 | 10.9 (7.2 to 14.6) | 9.4 (5.8 to 13) |
| Year 2 | 13.9 (9.7 to 18.2) | 11.2 (7.3 to 15.1) |
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.
| RBC packs | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Number of RBC Packs | 0.4 ± 1.20 | 0.4 ± 1.98 |
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.
| mL | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Volume of RBC Transfused | 97.0 ± 112.2 | 334.63 ± 508.40 |
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).
| Participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Number of Particpants Who Received RBC Transfusions | 38 | 28 |
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.
| Percentage of participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Year 0.5 | 4 (1.8 to 6.2) | 2.1 (0.4 to 3.8) |
| Year 1 | 9.3 (6 to 12.7) | 6.5 (3.5 to 9.5) |
| Year 1.5 | 13.3 (9.3 to 17.3) | 9.4 (5.8 to 13) |
| Year 2 | 16.7 (12.2 to 21.2) | 11.2 (7.3 to 15.1) |
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.
| Participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Number of Participants Who Received Rescue Therapy (Composite of RBC Transfusions (All Participants) and Darbepoetin Alfa Use (Roxadustat Treated Participants Only) | 46 | 28 |
Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg.
| mg per month | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Weeks 37 to 52 | 11.028 ± 64.282 | 13.208 ± 46.408 |
| Weeks 53 to 104 | 18.702 ± 68.074 | 31.315 ± 95.306 |
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 | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Year 0.5 | 4.3 (2 to 6.5) | 11.8 (8 to 15.6) |
| Year 1 | 10 (6.5 to 13.5) | 19.2 (14.5 to 23.9) |
| Year 1.5 | 15.9 (11.5 to 20.2) | 24.2 (19 to 29.4) |
| Year 2 | 24.9 (18.8 to 31) | 29.1 (23.1 to 35.1) |
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).
| Percentage of Participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| During efficacy emergent period | 50.6 | 52.7 |
| During day 1 to week 36 | 55.3 | 55.1 |
| During week 37 to 52 | 55.6 | 55.4 |
| During week 53 to 104 | 53.1 | 50.6 |
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.
| mmol/L | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to week 8 | -0.92 ± 0.98 | -0.046 ± 0.836 |
| Change from BL to week 28 | -0.531 ± 1.153 | 0.016 ± 0.953 |
| Change from BL to week 52 | -0.524 ± 1.232 | -0.111 ± 1.097 |
| Change from BL to week 104 | -0.695 ± 1.284 | -0.197 ± 1.171 |
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.
| Ratio | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to Week 8 | -0.209 ± 0.665 | -0.049 ± 0.629 |
| Change from BL to Week 28 | 0.016 ± 0.893 | 0.053 ± 0.747 |
| Change from BL to Week 52 | 0.014 ± 1.095 | -0.065 ± 0.871 |
| Change from BL to Week 104 | -0.069 ± 1.579 | 0.012 ± 1.06 |
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.
| mmoL/L | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to week 8 | -0.729 ± 0.9 | -0.045 ± 0.787 |
| Change from BL to week 28 | -0.392 ± 1.098 | 0.02 ± 0.911 |
| Change from BL to week 52 | -0.383 ± 1.19 | -0.114 ± 1.062 |
| Change from BL to week 104 | -0.562 ± 1.162 | -0.15 ± 1.151 |
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.
| Grams per liter (g/L) | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to week 8 | -0.184 ± 0.222 | 0.026 ± 0.204 |
| Change from BL to week 28 | -0.104 ± 0.258 | 0.055 ± 0.217 |
| Change from BL to week 52 | -0.12 ± 0.254 | 0.027 ± 0.229 |
| Change from BL to week 104 | -0.116 ± 0.311 | -0.018 ± 0.242 |
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.
| Milligrams per deciliter (mg/dL) | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to week 8 | -16.5 ± 19.581 | -0.71 ± 17.791 |
| Change from BL to week 28 | -10.659 ± 23.644 | 0.091 ± 19.672 |
| Change from BL to week 52 | -10.74 ± 25.155 | -3.539 ± 23.811 |
| Change from BL to week 104 | -13.561 ± 25.461 | -2.038 ± 25.857 |
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.
| Ratio | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to week 8 | -0.031 ± 0.185 | -0.019 ± 0.13 |
| Change from BL to week 28 | -0.026 ± 0.208 | -0.034 ± 0.159 |
| Change from BL to week 52 | -0.025 ± 0.254 | -0.038 ± 0.191 |
| Change from BL to week 104 | -0.044 ± 0.238 | -0.009 ± 0.218 |
Missing category for fasting only includes non-fasting participants and the participants with missing values.
| Participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Weeks 12-28: Yes (Regardless Fasting Status) | 147 | 111 |
| Weeks 12-28: No (Regardless Fasting Status) | 20 | 33 |
| Weeks 12-28: Missing (Regardless Fasting Status) | 10 | 8 |
| Weeks 12-28: Yes (Fasting only) | 90 | 69 |
| Weeks 12-28: No (Fasting only) | 11 | 18 |
| Weeks 12-28: Missing (Fasting only) | 76 | 65 |
| Weeks 36-52: Yes (Regardless Fasting Status) | 129 | 104 |
| Weeks 36-52: No (Regardless Fasting Status) | 26 | 31 |
| Weeks 36-52: Missing (Regardless Fasting Status) | 22 | 17 |
| Weeks 36-52: Yes (Fasting only) | 78 | 57 |
| Weeks 36-52: No (Fasting only) | 15 | 22 |
| Weeks 36-52: Missing (Fasting only) | 84 | 73 |
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.
| Participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Weeks 12-28: Yes | 76 | 64 |
| Weeks 12-28: No | 228 | 212 |
| Week 12-28: Missing | 18 | 16 |
| Weeks 36-52: Yes | 80 | 64 |
| Weeks 36-52: No | 196 | 193 |
| Weeks 36-52: Missing | 46 | 35 |
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.
| Units on a scale | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to weeks 12-28 | 1.222 (0.54 to 1.904) | 2.29 (1.576 to 3.004) |
| Change from BL to weeks 36-52 | 1.083 (0.358 to 1.808) | 1.686 (0.939 to 2.433) |
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.
| Units on a scale | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to weeks 12-28 | 4.71 (3.558 to 5.861) | 5.238 (4.029 to 6.446) |
| Change from BL to weeks 36-52 | 3.661 (2.355 to 4.967) | 4.608 (3.252 to 5.964) |
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.
| Units on a scale | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to weeks 12-28 | 7.761 (5.501 to 10.02) | 8.665 (6.299 to 11.031) |
| Change from BL to weeks 36-52 | 5.492 (2.915 to 8.069) | 7.259 (4.593 to 9.925) |
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.
| Units on a scale | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to weeks 12-28 | 6.798 ± 17.830 | 6.876 ± 16.960 |
| Change from BL to weeks 36-52 | 5.602 ± 19.302 | 5.595 ± 19.922 |
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.
| Units on a scale | Roxadustat | 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 | 5.137 (3.498 to 6.776) | 4.353 (2.643 to 6.064) |
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).
| Percent work time | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to average in weeks 12-28 | -3.793 ± 32.987 | 0.842 ± 21 |
| Change from BL to average in weeks 36-52 | -0.078 ± 37.047 | 0.216 ± 23.483 |
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.
| Percent impairment | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to weeks 12-28 | -6.618 ± 22.419 | -2.433 ± 28.598 |
| Change from BL to weeks 36-52 | -7.879 ± 25.872 | 1.083 ± 23.102 |
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)+\[(1-(Q2/(Q2+Q4))x(Q5/10)\].
| Percent impairment | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to weeks 12-28 | -6.112 ± 23.21 | -1.217 ± 20.743 |
| Change From BL to weeks 36-52 | 2.817 ± 30.432 | 0.197 ± 23.431 |
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.
| Percent impairment | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Change from BL to weeks 12-28 | -9.581 ± 27.367 | -9.34 ± 27.09 |
| Change from BL to weeks 36-52 | -9.365 ± 28.956 | -8.17 ± 27.486 |
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.
| Percentage of Participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Week 8 | 76.1 | 79.4 |
| Week 12 | 83.7 | 83.6 |
| Week 28 | 83 | 81 |
| Week 52 | 79.3 | 79.8 |
| Week 76 | 73 | 74.9 |
| Week 104 | 71.8 | 76 |
| Last Assessment | 70.6 | 71.4 |
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.
| Picomoles per liter (pmol/L) | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Week 4 | -190.762 ± 241.695 | -159.174 ± 218.981 |
| Week 8 | -229.471 ± 255.677 | -208.356 ± 309.893 |
| Week 12 | -205.722 ± 271.752 | -201.587 ± 346.59 |
| Week 20 | -99.86 ± 334.486 | -140.26 ± 338.512 |
| Week 28 | -97.622 ± 366.153 | -121.574 ± 348.136 |
| Week 36 | -131.801 ± 355.463 | -120.424 ± 362.08 |
| Week 44 | -120.864 ± 368.902 | -60.149 ± 425.455 |
| Week 52 | -93.074 ± 521.433 | -72.383 ± 459.342 |
| Week 60 | -141.264 ± 355.419 | -47.714 ± 459.319 |
| Week 68 | -110.907 ± 422.28 | -14.283 ± 464.714 |
| Week 76 | -99.697 ± 412.982 | 3.424 ± 615.735 |
| Week 84 | -126.615 ± 403.693 | -1.351 ± 576.437 |
| Week 92 | -98.025 ± 460.364 | -26.73 ± 547.371 |
| Week 100 | -95.513 ± 486.758 | 31.391 ± 750.432 |
| Week 104 | -89.276 ± 476.167 | 26.454 ± 730.126 |
| EOS | 78.577 ± 680.524 | 119.157 ± 697.39 |
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.
| Percentage of saturation | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Week 4 | -6 ± 10.7 | -2.1 ± 11.5 |
| Week 8 | -5.9 ± 11.5 | -2.4 ± 10.6 |
| Week 12 | -2.4 ± 13.2 | -0.5 ± 12.3 |
| Week 20 | 1.6 ± 13.9 | 2.9 ± 11.6 |
| Week 28 | 1.1 ± 12.5 | 4 ± 12.5 |
| Week 36 | 1.6 ± 12 | 3.9 ± 11.5 |
| Week 44 | 0.6 ± 12 | 4.9 ± 12.9 |
| Week 52 | 1.3 ± 11.8 | 5.2 ± 13.2 |
| Week 60 | 0.4 ± 12.4 | 4.8 ± 12.7 |
| Week 68 | 1 ± 13.4 | 6.3 ± 13.1 |
| Week 76 | 0.1 ± 12.2 | 6 ± 13.7 |
| Week 84 | 1.1 ± 12.5 | 6.5 ± 13.9 |
| Week 92 | -0.2 ± 11.7 | 5.6 ± 13.8 |
| Week 100 | 0.6 ± 12.4 | 5.8 ± 14 |
| Week 104 | 0.5 ± 11.9 | 5 ± 13.3 |
| EOS | 5.3 ± 12.3 | 4.7 ± 13.9 |
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.
| Percentage of HbA1c | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Week 12 | 0.0021 ± 0.0071 | 0.001 ± 0.0073 |
| Week 28 | 0.0009 ± 0.0072 | 0.0015 ± 0.0067 |
| Week 36 | 0.0021 ± 0.0075 | 0.0021 ± 0.0073 |
| Week 44 | 0.0026 ± 0.0077 | 0.002 ± 0.0066 |
| Week 60 | 0.0025 ± 0.0083 | 0.0019 ± 0.0074 |
| Week 84 | 0.0024 ± 0.0093 | 0.0025 ± 0.0077 |
| Week 104 | 0.0018 ± 0.0086 | 0.002 ± 0.008 |
| EOS | 0.0031 ± 0.0087 | 0.0034 ± 0.0081 |
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.
| mg/dL | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Week 4 | 7 ± 62.8 | 10.3 ± 76.9 |
| Week 8 | 4.1 ± 60.1 | 1.3 ± 40.3 |
| Week 12 | 9.3 ± 64.5 | 7.1 ± 58.2 |
| Week 20 | 6.9 ± 69.4 | 4.3 ± 57.9 |
| Week 28 | 8.7 ± 66.9 | 2.8 ± 37.7 |
| Week 36 | 6.4 ± 52.5 | 3.6 ± 45.3 |
| Week 44 | 3.3 ± 44.7 | 0.4 ± 45.1 |
| Week 52 | 7.1 ± 69.7 | 1.1 ± 41.1 |
| Week 60 | 6.6 ± 65.6 | 6.3 ± 43.1 |
| Week 68 | 3.8 ± 66.1 | 5.5 ± 48.2 |
| Week 76 | 0.9 ± 41.9 | 5.8 ± 55.2 |
| Week 84 | 1.4 ± 49.1 | 12 ± 57.4 |
| Week 92 | 6 ± 69.5 | 2.1 ± 46.5 |
| Week 100 | 2.7 ± 45.3 | 4 ± 48.9 |
| Week 104 | -2.6 ± 60.7 | 1 ± 48.6 |
| Week 106 | -2.4 ± 31.2 | 9.2 ± 53.3 |
| EOS | 2.5 ± 58.2 | 9.8 ± 43.6 |
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.
| Geometric mean ratio | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Week 4 | 1.01 (0.99 to 1.03) | 0.97 (0.95 to 0.99) |
| Week 8 | 1.01 (0.98 to 1.03) | 0.96 (0.94 to 0.99) |
| Week 12 | 1.02 (1.00 to 1.05) | 0.95 (0.93 to 0.98) |
| Week 20 | 0.98 (0.95 to 1.01) | 0.93 (0.90 to 0.96) |
| Week 28 | 0.93 (0.89 to 0.96) | 0.89 (0.86 to 0.93) |
| Week 36 | 0.93 (0.89 to 0.97) | 0.89 (0.85 to 0.93) |
| Week 44 | 0.90 (0.86 to 0.93) | 0.89 (0.84 to 0.93) |
| Week 52 | 0.90 (0.86 to 0.94) | 0.88 (0.83 to 0.92) |
| Week 60 | 0.90 (0.86 to 0.94) | 0.86 (0.82 to 0.91) |
| Week 68 | 0.87 (0.83 to 0.91) | 0.84 (0.79 to 0.89) |
| Week 76 | 0.83 (0.78 to 0.88) | 0.84 (0.78 to 0.90) |
| Week 84 | 0.83 (0.78 to 0.88) | 0.83 (0.77 to 0.89) |
| Week 92 | 0.84 (0.79 to 0.90) | 0.85 (0.79 to 0.90) |
| Week 100 | 0.84 (0.78 to 0.89) | 0.86 (0.81 to 0.92) |
| Week 104 | 0.84 (0.79 to 0.90) | 0.84 (0.79 to 0.91) |
| Week 106 | 0.84 (0.78 to 0.90) | 0.86 (0.79 to 0.92) |
| EOS | 0.86 (0.81 to 0.91) | 0.85 (0.79 to 0.92) |
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.
| ml/min per 1.73 m^2 | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Rate of Progression of Chronic Kidney Disease Measured by eGFR Slope Over Time | -2.95 (-3.56 to -2.34) | -2.89 (-3.51 to -2.27) |
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.
| Geometric mean ratio | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Week 12 | 1.19 (1.07 to 1.34) | 1.23 (1.1 to 1.38) |
| Week 24 | 1.18 (1.06 to 1.33) | 1.22 (1.08 to 1.39) |
| Week 36 | 1.22 (1.07 to 1.4) | 1.18 (1.03 to 1.36) |
| Week 52 | 1.28 (1.1 to 1.49) | 1.1 (0.92 to 1.32) |
| Week 64 | 1.23 (1.03 to 1.46) | 1.11 (0.9 to 1.38) |
| Week 76 | 1.39 (1.14 to 1.7) | 1.18 (0.94 to 1.48) |
| Week 88 | 1.21 (0.97 to 1.5) | 1.1 (0.86 to 1.39) |
| Week 104 | 1.46 (1.17 to 1.82) | 1.18 (0.92 to 1.51) |
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.
| Percentage of Participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Year 0.5 | 12.9 (9.1 to 16.6) | 8.6 (5.3 to 11.9) |
| Year 1 | 27.4 (22.3 to 32.6) | 27.2 (21.9 to 32.6) |
| Year 1.5 | 38.2 (32.5 to 44) | 38.8 (32.9 to 44.7) |
| Year 2 | 46.5 (40.5 to 52.5) | 45.4 (39.2 to 51.5) |
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.
| Participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Number of Participants With End Stage Renal Disease (ESRD) | 110 | 107 |
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.
| Percentage of participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Year 0.5 | 14 (10.1 to 17.9) | 10.2 (6.7 to 13.8) |
| Year 1 | 30.9 (25.6 to 36.2) | 29.5 (24.1 to 34.9) |
| Year 1.5 | 42.1 (36.4 to 47.8) | 42.6 (36.6 to 48.5) |
| Year 2 | 49.9 (44 to 55.8) | 51 (44.9 to 57) |
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.
| Percentage of participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Year 0.5 | 12.7 (9 to 16.4) | 9.2 (5.8 to 12.6) |
| Year 1 | 27.1 (22 to 32.2) | 26.2 (21 to 31.4) |
| Year 1.5 | 37.1 (31.6 to 42.7) | 37.7 (31.9 to 43.5) |
| Year 2 | 42.9 (37.1 to 48.7) | 45.6 (39.6 to 51.7) |
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.
| Percentage of participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| Year 0.5 | 15.4 (11.3 to 19.5) | 13 (9 to 16.9) |
| Year 1 | 34.5 (29 to 40) | 35.5 (29.8 to 41.3) |
| Year 1.5 | 47.2 (41.3 to 53.1) | 50.2 (44.1 to 56.3) |
| Year 2 | 55.7 (49.7 to 61.7) | 59.3 (53.2 to 65.3) |
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.
| Participants | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| TEAE | 296 | 271 |
| Drug-Related TEAE | 78 | 66 |
| Serious TEAE | 209 | 181 |
| Drug-Related Serious TEAE | 18 | 9 |
| TEAE Leading to Death | 34 | 34 |
| Drug-Related TEAE Leading to Death | 2 | 0 |
| TEAE Leading to Withdrawal of Treatment | 25 | 11 |
| Drug-Related TEAE Leading to Withdraw of Treatment | 7 | 1 |
| TEAE NCI CTC Grades 3 or Higher | 181 | 164 |
Collected over From first dose of study drug up to end of study (up to week 108). Non-serious events are listed at a 4.95% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Roxadustat | 40/323 (12.4%) | 209/323 (64.7%) | 223/323 (69%) |
| Darbepoetin Alfa | 37/293 (12.6%) | 181/293 (61.8%) | 203/293 (69.3%) |
| Event | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| End stage renal diseaseRenal and urinary disorders | 108/323 | 106/293 |
| Glomerular filtration rate decreasedInvestigations | 26/323 | 25/293 |
| PneumoniaInfections and infestations | 21/323 | 14/293 |
| Cardiac failureCardiac disorders | 12/323 | 10/293 |
| Cardiac failure congestiveCardiac disorders | 2/323 | 10/293 |
| SepsisInfections and infestations | 7/323 | 9/293 |
| Arteriovenous fistula thrombosisInjury, poisoning and procedural complications | 9/323 | 5/293 |
| Acute myocardial infarctionCardiac disorders | 5/323 | 8/293 |
| HypertensionVascular disorders | 8/323 | 5/293 |
| Pyelonephritis acuteInfections and infestations | 1/323 | 7/293 |
| Event | Roxadustat | Darbepoetin Alfa |
|---|---|---|
| HypertensionVascular disorders | 93/323 | 97/293 |
| Oedema peripheralGeneral disorders | 48/323 | 36/293 |
| HyperkalaemiaMetabolism and nutrition disorders | 34/323 | 39/293 |
| NauseaGastrointestinal disorders | 35/323 | 24/293 |
| Glomerular filtration rate decreasedInvestigations | 33/323 | 28/293 |
| DiarrhoeaGastrointestinal disorders | 27/323 | 28/293 |
| Viral upper respiratory tract infectionInfections and infestations | 29/323 | 25/293 |
| HyperphosphataemiaMetabolism and nutrition disorders | 28/323 | 15/293 |
| Urinary tract infectionInfections and infestations | 17/323 | 24/293 |
| Iron deficiencyMetabolism and nutrition disorders | 20/323 | 24/293 |
The analysis population was the safety analysis set which consisted of all randomized participants who received at least one dose of study drug.
| Age, Continuous(Years) | Roxadustat | Darbepoetin Alfa | Total |
|---|---|---|---|
| Mean | 66.8 ± 13.6 | 65.7 ± 14.4 | 66.3 ± 14 |
| Sex: Female, Male(Participants) | Roxadustat | Darbepoetin Alfa | Total |
|---|---|---|---|
| Female | 178 | 164 | 342 |
| Male | 145 | 129 | 274 |
| Race/Ethnicity, Customized(Participants) | Roxadustat | Darbepoetin Alfa | Total |
|---|---|---|---|
| Race — Asian | 9 | 10 | 19 |
| Race — Black or African American | 8 | 2 | 10 |
| Race — White | 306 | 281 | 587 |
| Baseline Hb Value(Participants) | Roxadustat | Darbepoetin Alfa | Total |
|---|---|---|---|
| <=8.0 g/dL | 11 | 10 | 21 |
| >8.0 g/dL | 312 | 283 | 595 |
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PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Supporting information: Study protocol, Statistical analysis plan, Clinical study report
Time frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Data sharing details ↗ · www.clinicaltrials.astellas.com
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Studies of the drug tested here: Roxadustat
Renal Insufficiency, Chronic →