Pyrenees: Roxadustat in the Treatment of Anemia in End Stage Renal Disease (ESRD) Patients on Stable Dialysis
Sponsor
Astellas Pharma Europe B.V. (Industry)
Overall Status
Completed
CT.gov ID
NCT02278341
Collaborator
FibroGen (Industry)
838
143
2
43.5
5.9
0.1
Study Details
Study Description
Brief Summary
This study was conducted to explore a new therapy for anemia in participants with end stage renal disease (ESRD) on dialysis. Anemia is a reduced number of red blood cells or hemoglobin. Hemoglobin (which contains iron) is important for the transport of oxygen in your blood. The purpose of this study was to evaluate if roxadustat is effective and safe in the maintenance treatment of anemia in ESRD participants on stable dialysis. Roxadustat was compared to epoetin alfa and darbepoetin alfa, commercially available medicines for treatment of anemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This study consisted of three study periods as follows:
-
Screening Period: up to 6 weeks
-
Treatment Period: a minimum of 52 weeks up to a maximum of 104 weeks
-
Follow-up Period: 4 weeks
Study Design
Study Type:
Interventional
Actual Enrollment
:
838 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Open-Label, Active-Controlled Study to Evaluate the Efficacy and Safety of Roxadustat in the Maintenance Treatment of Anemia in End Stage Renal Disease Patients on Stable Dialysis
Actual Study Start Date
:
Nov 21, 2014
Actual Primary Completion Date
:
Jun 8, 2017
Actual Study Completion Date
:
Jul 6, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Roxadustat Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. |
Drug: Roxadustat
Participants received initial dose of roxadustat orally as a tablet in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Other Names:
Drug: Iron
Oral iron treatment was recommended for supplementation to support erythropoiesis and as first-line treatment for iron deficiency, unless participant was intolerant to this treatment. For participants receiving roxadustat the recommended daily dose was 200 mg of elemental iron. Participants were advised to take roxadustat at least 1 hour before or 1 hour after oral iron. Intravenous iron supplementation for participants receiving roxadustat was allowed if all of the following criteria were met: The participant's Hb level had not responded adequately to roxadustat following two consecutive dose increases or reached the maximum dose limit, and participant's ferritin was < 100 ng/mL (< 220 pmol/L) or TSAT < 20%, or the participant was intolerant of oral iron therapy. For participants treated with epoetin alfa or darbepoetin alfa, IV iron supplementation was given according to standard of care.
|
| Active Comparator: ESA (Erythropoiesis Stimulating Agent) treatment Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from the epoetin alfa to darbepoetin alfa or vice versa. |
Drug: Epoetin alfa
Participants received epoetin alfa via intravenous or subcutaneous injection, once a week, twice a week, or three times a week (TIW). Epoetin alfa dosage was adjusted to maintain Hb level within the target range. Dosing of epoetin alfa was per UK SmPC of Eprex®. Participants received IV iron supplementation according to the standard of care.
Other Names:
Drug: Darbepoetin alfa
Participants received darbepoetin alfa via intravenous or subcutaneous injection, once a week or once every other week. Darbepoetin alfa dosage was adjusted to maintain Hb level within the target range. Dosing of darbepoetin alfa was per EU SmPC of Aranesp®. Participants received IV iron supplementation according to the standard of care.
Other Names:
Drug: Iron
Oral iron treatment was recommended for supplementation to support erythropoiesis and as first-line treatment for iron deficiency, unless participant was intolerant to this treatment. For participants receiving roxadustat the recommended daily dose was 200 mg of elemental iron. Participants were advised to take roxadustat at least 1 hour before or 1 hour after oral iron. Intravenous iron supplementation for participants receiving roxadustat was allowed if all of the following criteria were met: The participant's Hb level had not responded adequately to roxadustat following two consecutive dose increases or reached the maximum dose limit, and participant's ferritin was < 100 ng/mL (< 220 pmol/L) or TSAT < 20%, or the participant was intolerant of oral iron therapy. For participants treated with epoetin alfa or darbepoetin alfa, IV iron supplementation was given according to standard of care.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline (BL) to the Average Hemoglobin (Hb) in Weeks 28-36 Without Rescue Therapy [EU (EMA)] [Baseline and weeks 28 to 36]
Baseline Hb was defined as the mean of four central laboratory Hb values; four latest Hb values prior or on the same date as the first study drug intake. For participants who did not have an available Hb value during the week 28-36 period, imputation rules were applied. For analyses without rescue therapy, participants who used rescue therapy after the initiation of rescue therapy were set to missing for 6 weeks from the start date of rescue therapy. If no Hb value was available, an imputation technique was used, with the mean of all available values from Day 1 to minimum (End of Efficacy Emergent Period) carried forward.
- Change From BL to the Average Hb in Weeks 28 to 52 Regardless of Rescue Therapy [US (FDA)] [Baseline and weeks 28 to 52]
Baseline Hb was defined as the mean of four central laboratory Hb values: four latest Hb values prior or on the same date as first study drug intake. Change from baseline to the average Hb are observed values. Missing hemoglobin data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the Monte Carlo Markov Chain (MCMC) imputation model with treatment, baseline hemoglobin, randomization stratification factors and the available non missing hemoglobin for each scheduled week.
Secondary Outcome Measures
- Percentage of Participants With Hb Response During Weeks 28 to 36 [Weeks 28 to 36]
Hb response during weeks 28-36, was defined as mean Hb from 10-12 g/dL without receiving rescue therapy in the 6 weeks prior to, or during, the evaluation period. The percentages and 95% CI were unadjusted, the exact method of Clopper-Pearson was used for 95% CI. 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).
- Change From BL in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28 [Baseline and weeks 12 to 28]
Baseline LDL was defined as the LDL value on Day 1. If this value was missing, the latest value prior to first study drug administration was used.
- Mean Monthly Intravenous (IV) Iron Use [Day 1 to week 36]
Participants with no or missing medication records of IV Iron have their monthly IV Iron use set to 0 mg. For participants who took IV Iron, but without a dosing frequency, the average values were set to missing.
- Change From BL in Short Form-36 (SF-36) Health Survey Physical Functioning (PF) Sub-score to the Average of Weeks 12 to 28 [Baseline and weeks 12 to 28]
Baseline SF-36 PF was defined as the SF-36 PF value on Day 1.The SF-36 is a Quality of Life (QoL) instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 contains 36 items that measure eight scales: (1) physical functioning (PF); (2) role limitations due to physical health problems (RP); (3) bodily pain (BP); (4) social functioning (SF); (5) general health perceptions (GH); (6) role limitations due to emotional problems (RE); (7) vitality, energy or fatigue (VT); and (8) mental health(MH). Each scale is transformed into 0-100 score, with higher scores indicating better health status. The SF-36 PF consists of 11 questions focused on health and ability to do usual activities, with higher scores indicating better health status.
- Change From BL in SF-36 Vitality (VT) Sub-score to the Average of Weeks 12 to 28 [Baseline and weeks 12 to 28]
Baseline VT Subscore was defined as the VT value on Day 1. The SF-36 is a QoL instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 vitality has four questions with score range from 0-100 with higher scores indicating better vitality status.
- Change From BL in Mean Arterial Pressure (MAP) to the Average of Weeks 20 to 28 [Baseline and weeks 20 to 28]
Baseline MAP was defined as the MAP value on Day 1. If this value was missing, the latest value prior to first study drug administration was used. Mean Arterial Pressure (MAP) is derived as: MAP = (2/3)*DBP + (1/3)*SBP.
- Time to First Occurrence of an Increase in Blood Pressure [Weeks 1 to 36]
Increase in Blood Pressure was defined as either: Systolic Blood Pressure (SBP) ≥ 170 mmHg and an increase from BL ≥ 20 mmHg, or as: Diastolic Blood Pressure (DBP) ≥ 100 mmHg and an increase from BL ≥ 15 mmHg. For participants who have 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 and the 95% confidence interval was calculated with Greenwood's formula.
- Change From BL in Mean Arterial Pressure (MAP) to the Average MAP Value of Weeks 20 to 28 [Baseline and weeks 20 to 28]
Baseline MAP was defined as the MAP value on day 1. If this value was missing, the latest value prior to first study drug administration was used. Mean Arterial Pressure (MAP) is derived as: MAP = (2/3)*DBP + (1/3)*SBP.
- Time to First Occurrence of an Increase in Blood Pressure [Weeks 1 to 36]
Increase in Blood Pressure was defined as either: SBP ≥ 170 mmHg and an increase from BL ≥ 20 mmHg, or as: DBP ≥ 100 mmHg and an increase from BL ≥ 15 mmHg. 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 With a Hb Response During Weeks 28 and 36 Regardless of Use of Rescue Therapy [Weeks 28 to 36]
Hb response was defined as mean Hb during weeks 28 to 36 within the target range of 10.0 to 12.0 g/dL. The percentages and 95% CI are unadjusted, the exact method of Clopper-Pearson was used for 95% CI.
- Change From BL in Hb to Each Postdosing Time Point [Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18,20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72,76, 80, 84, 88, 92, 96, 100, and 104]
Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose).
- Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy [Weeks 28 to 36, 44 to 52, and 96 to 104]
Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose). Averaged Hb values over weeks 28-36, weeks 44-52 and weeks 96-104 are observed values.
- Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy [Baseline and weeks 28 to 36, 44 to 52, and 96 to 104]
Change from baseline to the average Hb are observed values. Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose).
- Percentage of Hb Values ≥ 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy [Weeks 28-36, 44-52 and 96-104]
Percentage for each participant was calculated as Number of Hb values >= 10.0 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 Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy [Weeks 28-36, 44-52 and 96-104]
Percentage for each participant was calculated as 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.
- Number of Hospitalizations [Baseline to End of Treatment (EOT) (Up to week 104)]
The number of hospitalizations per participant were calculated during the Efficacy Emergent Period. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). It included all Non-Hemodialysis (HD) hospitalizations. The HD days were not counted as hospitalizations, even when performed overnight.
- Number of Days of Hospitalization Per Year [Baseline to EOT (Up to week 104)]
The number of days of hospitalizations per year was calculated as the sum of the durations of all non-HD hospitalizations in days (Date of discharge - Date of admission + 1)] / (duration of efficacy emergent period in days / 365.25). In case of missing dates, the hospitalization duration was imputed by the average duration per stay derived from the participants with non-missing duration within the same treatment group.
- Time to First Hospitalization [Baseline to EOT (Up to week 104)]
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. For participants without hospitalization, the time to censoring was calculated as: (Date of End of Efficacy Emergent Period - Analysis Date of first dose intake + 1) / 365.25. 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.
- Time to First Use of Rescue Therapy [Baseline to EOT (Up to week 104)]
Rescue therapy was defined as red blood cell (RBC) transfusion for both treatment groups and ESA for roxadustat participants. Only rescue medication that was started during the study treatment and up to end of efficacy emergent period was taken into account and considered as use of rescue medication. For participants who have experienced more than one use of rescue therapy, 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.
- Time to First RBC Transfusion [Baseline to EOT (Up to week 104)]
For participants who have experienced more than one RBC transfusion, only their first event following study treatment was used. For RBC transfusions, when the number of units was not given but the volume transfused was, the number of units were estimated by volume transfused/250 mL (for transfusion of packed cell units) or volume transfused/500 mL (for transfusion of full blood). Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
- Mean Monthly Number of RBC Packs Per Participant [Baseline to EOT (Up to week 104)]
During efficacy emergent period, the mean monthly number of RBC packs was calculated as the sum of blood volume and units transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. Participants without medication records of RBC have their number of RBC packs and volume set to 0.
- Mean Monthly Volume of RBC Transfusion Per Participant [Baseline to EOT (Up to week 104)]
During Efficacy Emergent Period, the mean monthly volume of blood transfused was calculated as the sum of blood volume and units transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period).
- Time to First Use of IV Iron Supplementation [Baseline to EOT (Up to week 104)]
For participants who have 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.
- Mean Monthly Intravenous (IV) Iron Per Participant During Weeks 37-52 and Weeks 53-104 [Weeks 37-52 and weeks 53-104]
Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg.
- Percentage of Participants With Oral Iron Use Only [Baseline to EOT (Up to week 104)]
Percentage of participants with/without IV iron only was calculated based on total number of participants within the Efficacy Emergent Period. The Efficacy Emergent Period is defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period).
- Change From BL to Each Post-dosing Study Visit in Total Cholesterol [Baseline and weeks 8, 28, 52, 104]
Baseline assessment was the assessment from Day 1 visit. If baseline value was missing, then the latest screening period value was used as the baseline regardless of fasting status.
- Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio [Baseline and weeks 8, 28, 52, 104]
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
- Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol [Baseline and weeks 8, 28, 52, 104]
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
- Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) [Baseline and weeks 8, 28, 52, 104]
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
- Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) [Baseline and weeks 8, 28, 52, 104]
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
- Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio [Baseline and weeks 8, 28, 52, 104]
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used.
- Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 [Weeks 12 to 28]
Missing category for Fasting Only includes non-fasting participants and the participants with missing values.
- Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal [Weeks 12 to 28]
Achieved antihypertensive treatment goal was defined as SBP < 140 mmHg and DBP < 90 mmHg over an evaluation period based on the average of available values in weeks 12-28 (pre-dialysis).
- Change From BL to the Average of Weeks 12 to 28 in SF-36 Physical Component Score (PCS) [Baseline and weeks 12 to 28]
Baseline SF-36 PCS was defined as the SF-36 PCS value on Day 1. SF-36 contains 36-item that measures 8 scales with scores ranging from 0-100: physical functioning (PF); role limitations due to physical health problems (RP); bodily pain (BP); social functioning (SF); general health perceptions (GH); role limitations due to emotional problems (RE); vitality, energy or fatigue (VT); and mental health (MH). These scores are normed to the US population (norm-based scoring had very little impact on results when data was collected in Western European countries) to have a mean of 50 and standard deviation of 10. The PCS was calculated based on all 8 scales and ranges from 5.02-79.78. For each of these above scales, higher scores always indicating better health status.
- Change From BL to the Average of Weeks 12 to 28 in Anemia Subscale (AnS) ("Additional Concerns") of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score [Baseline and weeks 12 to 28]
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 Anemia Subscale (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. For the above score, a higher score indicates better QoL.
- Change From BL to the Average Value of Weeks 12 to 28 in Total FACT-An Score [Baseline and weeks 12 to 28]
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 (PWB) - 7 items, functional (FWB) - 7 items, social/family (SWB) - 7 items, and emotional (EWB) - 6 items. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia. The total score is obtained by summation of the scores from PWB, SWB, EWB, FWB and AnS. The FACT-An Total Score scale range is 0-188. A higher score indicates better QoL.
- Change From BL to the Average of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score [Baseline and weeks 12 to 28]
Baseline assessment was defined as the value on Day 1. The EuroQol Questionnaire -5 Dimensions -5 Levels (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 visual analogue scale (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.
- Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) [Baseline and weeks 8, 12, 28, 36, 52, 76, 104]
The PGIC is a patient-rated instrument that measures 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 includes very much improved, much improved and minimally improved.
- Change From BL in Serum Hepcidin [Baseline and weeks 4, 12, 20, 36, 52, 104, and End of Study (EOS - up to 108 weeks)]
Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
- Change From BL in Serum Ferritin [Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104, and EOS (up to 108 weeks)]
Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
- Change From BL in Transferrin Saturation (TSAT) [Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 and EOS (up to 108 weeks)]
Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
- Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) [Baseline and weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to 108 weeks)]
Percentage of change from baseline to each study visit were calculated for HbA1c. Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Baseline up to EOS (Up to week 108)]
Safety was assessed by evaluation of the following variables: (TEAEs; frequency, severity, seriousness, and relationship to study drug), Vital signs (systolic and diastolic blood pressure, pulse, respiratory rate and weight), Clinical laboratory variables (hematology, biochemistry including liver enzymes and total bilirubin, and urinalysis), Physical examination, 12-lead electrocardiogram (ECG) and Vascular Access Thrombosis. All AEs collected during the Safety Emergent Period were counted as TEAE. The TEAE was defined as an adverse event (AE) if it was observed after starting administration of the roxadustat or ESA. Any clinically significant abnormalities were reported as an AEs. All reported deaths after the first study drug administration and up to 28 days after the Analysis Date of Last Dose and considering last dosing frequency.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Main Inclusion:
-
Participant is on stable hemodialysis (HD), hemodiafiltration (HDF) or peritoneal dialysis (PD) treatment with the same mode of dialysis for ≥4 months prior to randomization.
-
Participant is on IV or SC epoetin or IV or SC darbepoetin alfa treatment for ≥8 weeks prior to randomization with stable weekly doses (during 4 weeks prior to randomization).
-
Mean of the participant's three most recent Hb values, as measured by central laboratory, during the Screening Period.
-
Participant's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are ≤3 x upper limit of normal (ULN), and total bilirubin (TBL) is ≤1.5 x ULN
Exclusion Criteria:
Main Exclusion:
-
Participant has received a red blood cell (RBC) transfusion within 8 weeks prior to randomization.
-
Participant has a known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than Chronic Kidney Disease (CKD).
-
Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thrombo-embolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
-
Participant has had uncontrolled hypertension, in the opinion of the investigator, within 2 weeks prior to randomization.
-
Participant has a history of malignancy, except for the following: cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps.
-
Participant has had any prior organ transplant (that has not been explanted), or participant is scheduled for organ transplantation.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Site BE32004 | Brussels | Flemish Brabant | Belgium | 1200 |
| 2 | Site BE32001 | Aalst | Belgium | 9300 | |
| 3 | Site BE32019 | Antwerpen | Belgium | 2020 | |
| 4 | Site BE32002 | Antwerp | Belgium | 2060 | |
| 5 | Site BE32012 | Baudour | Belgium | 7331 | |
| 6 | Site BE32017 | Bonheiden | Belgium | 2820 | |
| 7 | Site BE32003 | Leuven | Belgium | 3000 | |
| 8 | Site BE32013 | Liege | Belgium | 4000 | |
| 9 | Site BE32011 | Roeselare | Belgium | 8800 | |
| 10 | Site BG35925 | Blagoevgrad | Bulgaria | 2700 | |
| 11 | Site BG35931 | Haskovo | Bulgaria | 6300 | |
| 12 | Site BG35915 | Pleven | Bulgaria | 5800 | |
| 13 | Site BG35909 | Plovdiv | Bulgaria | 4000 | |
| 14 | Site BG35919 | Plovdiv | Bulgaria | 4003 | |
| 15 | Site BG35920 | Rousse | Bulgaria | 7002 | |
| 16 | Site BG35938 | Shumen | Bulgaria | 9700 | |
| 17 | Site BG35924 | Sofia | Bulgaria | 1309 | |
| 18 | Site BG35906 | Sofia | Bulgaria | 1431 | |
| 19 | Site BG35921 | Sofia | Bulgaria | 1527 | |
| 20 | Site BG35907 | Stara Zagora | Bulgaria | 6000 | |
| 21 | Site BG35916 | Varna | Bulgaria | 9000 | |
| 22 | Site BG35918 | Varna | Bulgaria | 9010 | |
| 23 | Site BG35903 | Veliko Tarnovo | Bulgaria | 5000 | |
| 24 | Site BG35937 | Yambol | Bulgaria | 8600 | |
| 25 | Site HR38509 | Zagreb | Grad Zagreb | Croatia | 10000 |
| 26 | Site HR38508 | Cakovec | Croatia | 40000 | |
| 27 | Site HR38505 | Karlovac | Croatia | 47000 | |
| 28 | Site HR38507 | Osijek | Croatia | 31 000 | |
| 29 | Site HR38506 | Rijeka | Croatia | 51000 | |
| 30 | Site HR38504 | Slavonski Brod | Croatia | 35000 | |
| 31 | Site HR38501 | Zadar | Croatia | 23 000 | |
| 32 | Site CZ42008 | Liberec | Czechia | 46063 | |
| 33 | Site CZ42021 | Praha 6 | Czechia | 169 00 | |
| 34 | Site CZ42015 | Rakovnik | Czechia | 26929 | |
| 35 | Site FR33005 | Amiens cedex 1 | France | 80054 | |
| 36 | Site FR33010 | La Tronche | France | 38701 | |
| 37 | Site FR33055 | Saint Ouen | France | 93400 | |
| 38 | Site FR33007 | Saint Priez En Jarez | France | 42270 | |
| 39 | Site FR33056 | Valenciennes | France | 59300 | |
| 40 | Site GE99503 | Tbilisi | Georgia | 0144 | |
| 41 | Site GE99504 | Tbilisi | Georgia | 0144 | |
| 42 | Site GE99508 | Tbilisi | Georgia | 159 | |
| 43 | Site DE49056 | Dormagen | Nordrhein-Westfalen | Germany | 41540 |
| 44 | Site DE49067 | Berlin | Germany | 10117 | |
| 45 | Site DE49073 | Cloppenburg | Germany | 49661 | |
| 46 | Site DE49008 | Dresden | Germany | 01307 | |
| 47 | Site DE49054 | Dusseldorf | Germany | 40210 | |
| 48 | Site DE49020 | Frankfurt am Main | Germany | 60590 | |
| 49 | Site DE49065 | Hamburg | Germany | 23397 | |
| 50 | Site DE49075 | Heilbronn | Germany | 74076 | |
| 51 | Site DE49001 | Kaiserslautern | Germany | 67655 | |
| 52 | Site DE49070 | Muenchen | Germany | 81695 | |
| 53 | Site DE49002 | Solingen | Germany | 42653 | |
| 54 | Site DE49071 | Villingen-Schwenningen | Germany | 78052 | |
| 55 | Site HU36033 | Baja | Hungary | 6500 | |
| 56 | Site HU36036 | Esztergom | Hungary | 2500 | |
| 57 | Site HU36031 | Gyor | Hungary | 9002 | |
| 58 | Site HU36026 | Kaposvar | Hungary | H 7400 | |
| 59 | Site HU36027 | Kistarcsa | Hungary | 2143 | |
| 60 | Site HU36032 | Pecs | Hungary | 7624 | |
| 61 | Site HU36035 | Pecs | Hungary | 7633 | |
| 62 | Site HU36034 | Salgotarjan | Hungary | 3100 | |
| 63 | Site HU36004 | Szeged | Hungary | 6724 | |
| 64 | Site HU36046 | Szekesfehervar | Hungary | 8000 | |
| 65 | Site HU36006 | Szombathely | Hungary | H 9700 | |
| 66 | Site HU36003 | Zalsaegerszeg | Hungary | 8900 | |
| 67 | Site IT39028 | Prato | Frazione Di Galciana | Italy | 59100 |
| 68 | Site IT39039 | Cremona | Lombardia | Italy | 26100 |
| 69 | Site IT39014 | Mestre | Venezia | Italy | 30174 |
| 70 | Site IT39010 | Brescia | Italy | 25123 | |
| 71 | Site IT39008 | Lecco | Italy | 23900 | |
| 72 | Site IT39006 | Milano | Italy | 20162 | |
| 73 | Site IT39037 | Modena | Italy | 41124 | |
| 74 | Site IT39022 | Padova | Italy | 35128 | |
| 75 | Site IT39036 | Pavia | Italy | 27100 | |
| 76 | Site IT39005 | Roma | Italy | 122 | |
| 77 | Site IT39035 | Torino | Italy | 10126 | |
| 78 | Site IT39032 | Trieste | Italy | 34142 | |
| 79 | Site PL48002 | Katowice | Poland | 40 027 | |
| 80 | Site PL48001 | Krakow | Poland | 30 501 | |
| 81 | Site PL48013 | Szczecin | Poland | 70-111 | |
| 82 | Site PL48005 | Warszawa | Poland | 00 507 | |
| 83 | Site PL48006 | Wroclaw | Poland | 50-556 | |
| 84 | Site PL48009 | Wroclaw | Poland | 51 124 | |
| 85 | Site PL48014 | Zamosc | Poland | 20-400 | |
| 86 | Site PT35121 | Almada | Portugal | 2800-455 | |
| 87 | Site PT35127 | Aveiro | Portugal | 3800-266 | |
| 88 | Site PT35139 | Cascais | Portugal | 2750-663 | |
| 89 | Site PT35117 | Faro | Portugal | 8005-546 | |
| 90 | Site PT35128 | Gaeiras | Portugal | 2510-702 | |
| 91 | Site PT35114 | Leiria | Portugal | 2400-441 | |
| 92 | Site PT35102 | Porto | Portugal | 4099-001 | |
| 93 | Site PT35122 | Setubal | Portugal | 2900-655 | |
| 94 | Site RO40018 | Bucharest | Romania | 011794 | |
| 95 | Site RO40015 | Bucharest | Romania | ||
| 96 | Site RO40019 | Bucharest | Romania | ||
| 97 | Site RO40003 | Bucuresti | Romania | 22328 | |
| 98 | Site RO40004 | Oradea | Romania | 410562 | |
| 99 | Site RU70008 | Kaluga | Russian Federation | 248007 | |
| 100 | Site RU70051 | Moscow | Russian Federation | 119992 | |
| 101 | Site RU70005 | Moscow | Russian Federation | 125284 | |
| 102 | Site RU70003 | Nizhny Novgorod | Russian Federation | 603032 | |
| 103 | Site RU70004 | Omsk | Russian Federation | 644112 | |
| 104 | Site RU70014 | Rostov-on-Don | Russian Federation | 344029 | |
| 105 | Site RU70072 | Saint Petersburg | Russian Federation | 190103 | |
| 106 | Site RU70002 | Saint Petersburg | Russian Federation | 197089 | |
| 107 | Site RU70011 | Saint-Petersburg | Russian Federation | 196247 | |
| 108 | Site RU70050 | Saint-Petersburg | Russian Federation | 197374 | |
| 109 | Site RU70030 | Sankt-Peterburg | Russian Federation | 197110 | |
| 110 | Site RU70006 | Smolensk | Russian Federation | 214006 | |
| 111 | Site RU70037 | Volgograd | Russian Federation | 404120 | |
| 112 | Site RU70001 | Yaroslavl | Russian Federation | 150062 | |
| 113 | Site RS38102 | Belgrade | Serbia | 11000 | |
| 114 | Site RS38105 | Belgrade | Serbia | 11000 | |
| 115 | Site RS38120 | Belgrade | Serbia | 11000 | |
| 116 | Site RS38104 | Belgrade | Serbia | ||
| 117 | Site RS38117 | Krusevac | Serbia | 37000 | |
| 118 | Site RS38101 | Nis | Serbia | ||
| 119 | Site RS38116 | Zrenjanin | Serbia | ||
| 120 | Site SK42102 | Koshice | Slovakia | 04001 | |
| 121 | Site SK42119 | Levice | Slovakia | 93401 | |
| 122 | Site SK42120 | Lučenec | Slovakia | 984 01 | |
| 123 | Site SK42113 | Puchov | Slovakia | 020 01 | |
| 124 | Site SK42116 | Senica | Slovakia | 90501 | |
| 125 | Site ES34041 | Santiago de Compostela | A Coruna | Spain | 15706 |
| 126 | Site ES34009 | El Ejido | Almeria | Spain | 04700 |
| 127 | Site ES34010 | Alcorcon | Madrid | Spain | 28922 |
| 128 | Site ES34030 | Majadahonda | Madrid | Spain | 28222 |
| 129 | Site ES34011 | Galdakao | Vizcaya | Spain | 48960 |
| 130 | Site ES34002 | Badalona-Barcelona | Spain | 8916 | |
| 131 | Site ES34008 | Barcelona | Spain | 08025 | |
| 132 | Site ES34006 | Barcelona | Spain | 08035 | |
| 133 | Site ES34017 | Jaen | Spain | 23007 | |
| 134 | Site ES34037 | Madrid | Spain | 28046 | |
| 135 | Site ES34052 | Valencia | Spain | 46017 | |
| 136 | Site GB44087 | Brighton | EastSussex | United Kingdom | BN2 5BD |
| 137 | Site GB44011 | Canterbury | Kent | United Kingdom | CT1 3NG |
| 138 | Site GB44080 | Stoke on Trent | Staffordshire | United Kingdom | ST4 6QG |
| 139 | Site GB44008 | Cambridge | United Kingdom | CB2 0QQ | |
| 140 | Site GB44010 | Hull | United Kingdom | HU3 2JZ | |
| 141 | Site GB44081 | Leicester | United Kingdom | LE5 4PW | |
| 142 | Site GB44079 | Liverpool | United Kingdom | L9 7AL | |
| 143 | Site GB44001 | Swansea | United Kingdom | SA6 6NL |
Sponsors and Collaborators
- Astellas Pharma Europe B.V.
- FibroGen
Investigators
- Study Director: Study Physician, Astellas Pharma Europe B.V.
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Astellas Pharma Europe B.V.
ClinicalTrials.gov Identifier:
NCT02278341
Other Study ID Numbers:
- 1517-CL-0613
- 2013-001497-16
First Posted:
Oct 30, 2014
Last Update Posted:
Feb 4, 2021
Last Verified:
Dec 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Astellas Pharma Europe B.V.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study population consisted of participants with end-stage renal disease (ESRD) who were on stable hemodialysis (HD) or peritoneal dialysis (PD), and were also on stable treatment with epoetin (i.e. epoetin alfa, beta, theta, zeta, delta or omega) or darbepoetin alfa for anemia. |
|---|---|
| Pre-assignment Detail | Participants were randomized in a 1:1 ratio to roxadustat or ESA (epoetin alfa or darbepoetin alfa). Randomization was stratified by 5 factors: previous ESA treatment, region, history of cardiovascular, cerebrovascular or thromboembolic diseases, average weekly ESA dose 4 weeks prior to randomization and the screening hemaglobin (Hb) value. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Period Title: Overall Study | ||
| STARTED | 415 | 421 |
| Received Treatment | 414 | 420 |
| COMPLETED | 297 | 329 |
| NOT COMPLETED | 118 | 92 |
Baseline Characteristics
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) | Total |
|---|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. | Total of all reporting groups |
| Overall Participants | 415 | 421 | 836 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
61
(13.8)
|
61.8
(13.4)
|
61.4
(13.6)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
169
40.7%
|
185
43.9%
|
354
42.3%
|
| Male |
246
59.3%
|
236
56.1%
|
482
57.7%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| WHITE |
405
97.6%
|
408
96.9%
|
813
97.2%
|
| BLACK OR AFRICAN AMERICAN |
6
1.4%
|
6
1.4%
|
12
1.4%
|
| ASIAN |
2
0.5%
|
3
0.7%
|
5
0.6%
|
| OTHER |
2
0.5%
|
4
1%
|
6
0.7%
|
| Baseline Hemoglobin (Hb) Value (Count of Participants) | |||
| <=11.0 g/dL |
267
64.3%
|
266
63.2%
|
533
63.8%
|
| >11.0 g/dL |
148
35.7%
|
155
36.8%
|
303
36.2%
|
| Baseline Mean Hb (g/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [g/dL] |
10.75
(0.62)
|
10.77
(0.62)
|
10.76
(0.62)
|
Outcome Measures
| Title | Change From Baseline (BL) to the Average Hemoglobin (Hb) in Weeks 28-36 Without Rescue Therapy [EU (EMA)] |
|---|---|
| Description | Baseline Hb was defined as the mean of four central laboratory Hb values; four latest Hb values prior or on the same date as the first study drug intake. For participants who did not have an available Hb value during the week 28-36 period, imputation rules were applied. For analyses without rescue therapy, participants who used rescue therapy after the initiation of rescue therapy were set to missing for 6 weeks from the start date of rescue therapy. If no Hb value was available, an imputation technique was used, with the mean of all available values from Day 1 to minimum (End of Efficacy Emergent Period) carried forward. |
| Time Frame | Baseline and weeks 28 to 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the Per Protocol Set (PPS) which consisted of all Full Analysis Set (FAS) participants who did not meet any of exclusion criteria from the PPS. The FAS consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose valid Hb assessment. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 354 | 381 |
| Least Squares Mean (95% Confidence Interval) [g/dL] |
0.428
|
0.193
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb and baseline Hb by visit as continuous variable. | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non Inferiority, Margin = -0.75 | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for non-inferiority test based on 1-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.235 | |
| Confidence Interval |
(2-Sided) 95% 0.132 to 0.339 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From BL to the Average Hb in Weeks 28 to 52 Regardless of Rescue Therapy [US (FDA)] |
|---|---|
| Description | Baseline Hb was defined as the mean of four central laboratory Hb values: four latest Hb values prior or on the same date as first study drug intake. Change from baseline to the average Hb are observed values. Missing hemoglobin data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the Monte Carlo Markov Chain (MCMC) imputation model with treatment, baseline hemoglobin, randomization stratification factors and the available non missing hemoglobin for each scheduled week. |
| Time Frame | Baseline and weeks 28 to 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the All Randomized, which consisted of participants who received at least one dose of study drug, and who had available data. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Least Squares Mean (95% Confidence Interval) [g/dL] |
0.363
|
0.192
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model includes treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable. Statistical analysis used was ANCOVA model with multiple imputations (MI). Missing hemoglobin data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the MCMC imputation model. | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-Inferiority, Margin = -0.75 | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for non-inferiority test based on 1-sided significance level. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.171 | |
| Confidence Interval |
(2-Sided) 95% 0.082 to 0.261 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Hb Response During Weeks 28 to 36 |
|---|---|
| Description | Hb response during weeks 28-36, was defined as mean Hb from 10-12 g/dL without receiving rescue therapy in the 6 weeks prior to, or during, the evaluation period. The percentages and 95% CI were unadjusted, the exact method of Clopper-Pearson was used for 95% CI. 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). |
| Time Frame | Weeks 28 to 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the PPS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 386 | 397 |
| Number (95% Confidence Interval) [Percentage of participants] |
84.2
20.3%
|
82.4
19.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | A generalized linear model was used to estimate the difference in response rates between the arms, as an approximation for the Miettinen and Nurminen method, adjusting for following covariates: region, previous ESA treatment, cardiovascular history and baseline Hb as categorical variables. | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority of roxadustat versus ESA (the non-inferiority margin for the difference between groups is -15%). | |
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | p-value for non-inferiority test based on 1-sided significance level. | |
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference of Percentages |
| Estimated Value | 2.3 | |
| Confidence Interval |
(2-Sided) 95% -2.9 to 7.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From BL in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28 |
|---|---|
| Description | Baseline LDL was defined as the LDL 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS, with participants who had available data. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 394 | 412 |
| Least Squares Mean (95% Confidence Interval) [mmol/L] |
-0.459
|
-0.082
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline LDL, baseline Hb as continuous variables. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | -0.377 | |
| Confidence Interval |
(2-Sided) 95% -0.451 to -0.304 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Mean Monthly Intravenous (IV) Iron Use |
|---|---|
| Description | Participants with no or missing medication records of IV Iron have their monthly IV Iron use set to 0 mg. For participants who took IV Iron, but without a dosing frequency, the average values were set to missing. |
| Time Frame | Day 1 to week 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS, with participants who had available data. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 419 |
| Least Squares Mean (95% Confidence Interval) [mg per month] |
21.6
|
53.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model includes treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | -31.9 | |
| Confidence Interval |
(2-Sided) 95% -41.4 to -22.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From BL in Short Form-36 (SF-36) Health Survey Physical Functioning (PF) Sub-score to the Average of Weeks 12 to 28 |
|---|---|
| Description | 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 measure eight scales: (1) physical functioning (PF); (2) role limitations due to physical health problems (RP); (3) bodily pain (BP); (4) social functioning (SF); (5) general health perceptions (GH); (6) role limitations due to emotional problems (RE); (7) vitality, energy or fatigue (VT); and (8) mental health(MH). Each scale is transformed into 0-100 score, with higher scores indicating better health status. The SF-36 PF consists of 11 questions focused on health and ability to do usual activities, with higher scores indicating better health status. |
| Time Frame | Baseline and weeks 12 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the PPS, with participants who had available data. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 376 | 391 |
| Least Squares Mean (95% Confidence Interval) [Units on a scale] |
0.050
|
-0.155
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model includes treatment arm, region, CV History, previous ESA treatment, visits (week 8, week 12, week 28) and visit by treatment as categorical variables, and baseline SF-36 PF, baseline Hb as continuous variables. | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | The margin for non-inferiority was -3. | |
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | p-value for non-inferiority test based on 1-sided significance level | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.205 | |
| Confidence Interval |
(2-Sided) 95% -0.649 to 1.059 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From BL in SF-36 Vitality (VT) Sub-score to the Average of Weeks 12 to 28 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the PPS, with participants who had available data. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 377 | 391 |
| Least Squares Mean (95% Confidence Interval) [Units on a scale] |
0.460
|
-0.396
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model includes treatment arm, region, CV History, previous ESA treatment, visits (week 8, week 12, week 28) and visit by treatment as categorical variables, and baseline SF-36 VT, baseline Hb as continuous variables. | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | The margin for non-inferiority was -3. | |
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.856 | |
| Confidence Interval |
(2-Sided) 95% -0.115 to 1.828 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From BL in Mean Arterial Pressure (MAP) to the Average of Weeks 20 to 28 |
|---|---|
| Description | 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. Mean Arterial Pressure (MAP) is derived as: MAP = (2/3)*DBP + (1/3)*SBP. |
| Time Frame | Baseline and weeks 20 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the PPS, with participants who had available data. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 373 | 388 |
| Least Squares Mean (95% Confidence Interval) [mmHg] |
-0.969
|
-0.120
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables, and baseline MAP, baseline Hb as continuous variables. | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | The margin for non-inferiority was 1. | |
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | p-value for non-inferiority test based on 1-sided significance level | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | -0.849 | |
| Confidence Interval |
(2-Sided) 95% -1.971 to 0.273 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to First Occurrence of an Increase in Blood Pressure |
|---|---|
| Description | Increase in Blood Pressure was defined as either: Systolic Blood Pressure (SBP) ≥ 170 mmHg and an increase from BL ≥ 20 mmHg, or as: Diastolic Blood Pressure (DBP) ≥ 100 mmHg and an increase from BL ≥ 15 mmHg. For participants who have 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 and the 95% confidence interval was calculated with Greenwood's formula. |
| Time Frame | Weeks 1 to 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the PPS, with participants who had available data. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. . | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 386 | 397 |
| Week 12 |
11.7
2.8%
|
11.1
2.6%
|
| Week 24 |
15.9
3.8%
|
15.4
3.7%
|
| Week 36 |
21.1
5.1%
|
23.5
5.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment, and adjusting on Hb at baseline as continuous covariate. Non-inferiority was declared if the upper bound of the 95% CI is below 1.3. | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority (hazard ratio margin of 1.3). | |
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | p-value for non-inferiority test based on 1-sided significance level. | |
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.924 | |
| Confidence Interval |
(2-Sided) 95% 0.669 to 1.276 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From BL in Mean Arterial Pressure (MAP) to the Average MAP Value of Weeks 20 to 28 |
|---|---|
| Description | 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. Mean Arterial Pressure (MAP) is derived as: MAP = (2/3)*DBP + (1/3)*SBP. |
| Time Frame | Baseline and weeks 20 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS, with participants who had available data. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 381 | 401 |
| Least Squares Mean (95% Confidence Interval) [mmHg] |
-0.739
|
-0.160
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables, and baseline MAP, baseline Hb as continuous variables. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.308 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | -0.579 | |
| Confidence Interval |
(2-Sided) 95% -1.694 to 0.536 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to First Occurrence of an Increase in Blood Pressure |
|---|---|
| Description | Increase in Blood Pressure was defined as either: SBP ≥ 170 mmHg and an increase from BL ≥ 20 mmHg, or as: DBP ≥ 100 mmHg and an increase from BL ≥ 15 mmHg. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. |
| Time Frame | Weeks 1 to 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS, with participants who had available data. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Week 12 |
11.6
2.8%
|
12.0
2.9%
|
| Week 24 |
16.1
3.9%
|
16.2
3.8%
|
| Week 36 |
21.2
5.1%
|
24.1
5.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment, and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI is lower than 1. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.582 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.915 | |
| Confidence Interval |
(2-Sided) 95% 0.668 to 1.254 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With a Hb Response During Weeks 28 and 36 Regardless of Use of Rescue Therapy |
|---|---|
| Description | Hb response was defined as mean Hb during weeks 28 to 36 within the target range of 10.0 to 12.0 g/dL. The percentages and 95% CI are unadjusted, the exact method of Clopper-Pearson was used for 95% CI. |
| Time Frame | Weeks 28 to 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Number (95% Confidence Interval) [Percentage of participants] |
83.1
20%
|
82.1
19.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | A generalized linear model was used to estimate the difference in response rates between the arms, as an approximation for the Miettinen and Nurminen method, adjusting for following covariates: region, previous ESA treatment, cardiovascular history and baseline Hb as categorical variables. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.609 |
| Comments | p-value for superiority test based on 2-sided significance level | |
| Method | Miettinen and Nurminen method | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference of Percentages |
| Estimated Value | 1.4 | |
| Confidence Interval |
(2-Sided) 95% -3.8 to 6.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From BL in Hb to Each Postdosing Time Point |
|---|---|
| Description | Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose). |
| Time Frame | Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18,20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72,76, 80, 84, 88, 92, 96, 100, and 104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Hb Change From BL to Week 1 |
0.232
|
0.068
|
| Hb Change From BL to Week 2 |
0.496
|
0.054
|
| Hb Change From BL to Week 3 |
0.633
|
0.071
|
| Hb Change From BL to Week 4 |
0.803
|
0.095
|
| Hb Change From BL to Week 5 |
0.723
|
-0.045
|
| Hb Change From BL to Week 6 |
0.868
|
0.138
|
| Hb Change From BL to Week 7 |
0.698
|
-0.031
|
| Hb Change From BL to Week 8 |
0.816
|
0.116
|
| Hb Change From BL to Week 10 |
0.640
|
-0.019
|
| Hb Change From BL to Week 12 |
0.732
|
0.139
|
| Hb Change From BL to Week 14 |
0.508
|
0.005
|
| Hb Change From BL to Week 16 |
0.613
|
0.244
|
| Hb Change From BL to Week 18 |
0.380
|
0.017
|
| Hb Change From BL to Week 20 |
0.501
|
0.217
|
| Hb Change From BL to Week 22 |
0.266
|
0.069
|
| Hb Change From BL to Week 24 |
0.262
|
0.075
|
| Hb Change From BL to Week 26 |
0.316
|
0.073
|
| Hb Change From BL to Week 28 |
0.549
|
0.342
|
| Hb Change From BL to Week 30 |
0.333
|
0.106
|
| Hb Change From BL to Week 32 |
0.310
|
0.111
|
| Hb Change From BL to Week 34 |
0.364
|
0.084
|
| Hb Change From BL to Week 36 |
0.482
|
0.225
|
| Hb Change From BL to Week 40 |
0.199
|
0.064
|
| Hb Change From BL to Week 44 |
0.335
|
0.252
|
| Hb Change From BL to Week 48 |
0.158
|
0.131
|
| Hb Change From BL to Week 52 |
0.385
|
0.186
|
| Hb Change From BL to Week 56 |
0.217
|
0.069
|
| Hb Change From BL to Week 60 |
0.368
|
0.171
|
| Hb Change From BL to Week 64 |
0.181
|
-0.093
|
| Hb Change From BL to Week 68 |
0.306
|
0.100
|
| Hb Change From BL to Week 72 |
0.109
|
-0.009
|
| Hb Change From BL to Week 76 |
0.401
|
0.189
|
| Hb Change From BL to Week 80 |
0.087
|
-0.015
|
| Hb Change From BL to Week 84 |
0.318
|
0.126
|
| Hb Change From BL to Week 88 |
0.026
|
-0.018
|
| Hb Change From BL to Week 92 |
0.357
|
0.154
|
| Hb Change From BL to Week 96 |
0.126
|
-0.058
|
| Hb Change From BL to Week 100 |
0.302
|
0.138
|
| Hb Change From BL to Week 104 |
0.232
|
0.133
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 1- The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.164 | |
| Confidence Interval |
(2-Sided) 95% 0.072 to 0.256 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 2- The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.443 | |
| Confidence Interval |
(2-Sided) 95% 0.339 to 0.546 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 3 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.561 | |
| Confidence Interval |
(2-Sided) 95% 0.451 to 0.672 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 4 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.708 | |
| Confidence Interval |
() 95% 0.588 to 0.828 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 5 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.768 | |
| Confidence Interval |
(2-Sided) 95% 0.645 to 0.890 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 6 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.729 | |
| Confidence Interval |
(2-Sided) 95% 0.604 to 0.855 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 7 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.729 | |
| Confidence Interval |
(2-Sided) 95% 0.603 to 0.856 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 8 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.700 | |
| Confidence Interval |
(2-Sided) 95% 0.574 to 0.826 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 10 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.659 | |
| Confidence Interval |
(2-Sided) 95% 0.530 to 0.788 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 12 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.593 | |
| Confidence Interval |
(2-Sided) 95% 0.459 to 0.727 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 14 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.503 | |
| Confidence Interval |
(2-Sided) 95% 0.366 to 0.640 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 16 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.369 | |
| Confidence Interval |
(2-Sided) 95% 0.229 to 0.510 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 18 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.363 | |
| Confidence Interval |
(2-Sided) 95% 0.230 to 0.496 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 20 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.284 | |
| Confidence Interval |
(2-Sided) 95% 0.154 to 0.414 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 22 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.003 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.197 | |
| Confidence Interval |
(2-Sided) 95% 0.065 to 0.329 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 24 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.004 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.187 | |
| Confidence Interval |
(2-Sided) 95% 0.059 to 0.316 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 26 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.243 | |
| Confidence Interval |
(2-Sided) 95% 0.113 to 0.373 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 28 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.002 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.207 | |
| Confidence Interval |
(2-Sided) 95% 0.074 to 0.340 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 30 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.227 | |
| Confidence Interval |
(2-Sided) 95% 0.096 to 0.358 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 32 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.004 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.199 | |
| Confidence Interval |
(2-Sided) 95% 0.064 to 0.334 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 34 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.279 | |
| Confidence Interval |
() 95% 0.150 to 0.409 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 36- The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.256 | |
| Confidence Interval |
(2-Sided) 95% 0.121 to 0.391 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 40 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.060 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.136 | |
| Confidence Interval |
(2-Sided) 95% -0.006 to 0.277 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 44 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.293 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.082 | |
| Confidence Interval |
(2-Sided) 95% -0.071 to 0.236 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 48 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.723 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.027 | |
| Confidence Interval |
(2-Sided) 95% -0.123 to 0.177 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 52 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.009 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.199 | |
| Confidence Interval |
(2-Sided) 95% 0.049 to 0.348 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 56 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.056 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.147 | |
| Confidence Interval |
(2-Sided) 95% -0.004 to 0.298 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 60 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.010 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.196 | |
| Confidence Interval |
(2-Sided) 95% 0.047 to 0.346 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 64 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.275 | |
| Confidence Interval |
(2-Sided) 95% 0.123 to 0.427 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 68 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.006 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.206 | |
| Confidence Interval |
(2-Sided) 95% 0.059 to 0.353 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 31
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 72 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.127 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.118 | |
| Confidence Interval |
(2-Sided) 95% -0.033 to 0.269 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 32
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 76 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.010 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.211 | |
| Confidence Interval |
(2-Sided) 95% 0.051 to 0.371 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 33
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 80 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.191 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.102 | |
| Confidence Interval |
(2-Sided) 95% -0.051 to 0.255 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 34
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 84 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.018 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.192 | |
| Confidence Interval |
(2-Sided) 95% 0.033 to 0.351 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 35
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 88 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.576 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.044 | |
| Confidence Interval |
(2-Sided) 95% -0.111 to 0.200 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 36
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 92 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.017 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.203 | |
| Confidence Interval |
(2-Sided) 95% 0.037 to 0.369 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 37
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 96 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.019 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.184 | |
| Confidence Interval |
(2-Sided) 95% 0.031 to 0.338 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 38
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 100 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.056 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.164 | |
| Confidence Interval |
() 95% -0.004 to 0.333 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 39
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Week 104 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.267 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.099 | |
| Confidence Interval |
(2-Sided) 95% -0.076 to 0.273 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy |
|---|---|
| Description | Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose). Averaged Hb values over weeks 28-36, weeks 44-52 and weeks 96-104 are observed values. |
| Time Frame | Weeks 28 to 36, 44 to 52, and 96 to 104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Average Hb Over Weeks 28-36 |
11.183
|
10.946
|
| Average Hb Over Weeks 44-52 |
11.099
|
10.994
|
| Average Hb Over Weeks 96-104 |
11.007
|
10.858
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Weeks 28-36 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value for superiority test based on 2-sided significance level. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.237 | |
| Confidence Interval |
(2-Sided) 95% 0.127 to 0.347 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Weeks 44-52 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.086 |
| Comments | p-value for superiority test based on 2-sided significance level | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.105 | |
| Confidence Interval |
(2-Sided) 95% -0.015 to 0.225 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Weeks 96-104 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.031 |
| Comments | p-value for superiority test based on 2-sided significance level | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.149 | |
| Confidence Interval |
(2-Sided) 95% 0.014 to 0.284 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy |
|---|---|
| Description | Change from baseline to the average Hb are observed values. Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose). |
| Time Frame | Baseline and weeks 28 to 36, 44 to 52, and 96 to 104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Hb Change From BL to Weeks 28-36 |
0.408
|
0.173
|
| Hb Change From BL to Weeks 44-52 |
0.298
|
0.194
|
| Hb Change From BL to Weeks 96-104 |
0.225
|
0.076
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Weeks 28-36 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.235 | |
| Confidence Interval |
(2-Sided) 95% 0.125 to 0.346 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Weeks 44-52 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.110 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.104 | |
| Confidence Interval |
(2-Sided) 95% -0.024 to 0.232 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Weeks 96-104 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.036 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.149 | |
| Confidence Interval |
(2-Sided) 95% 0.010 to 0.288 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Hb Values ≥ 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy |
|---|---|
| Description | Percentage for each participant was calculated as Number of Hb values >= 10.0 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 28-36, 44-52 and 96-104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Weeks 28-36 |
93.002
(18.320)
|
87.286
(25.114)
|
| Weeks 44-52 |
89.421
(24.267)
|
86.914
(25.366)
|
| Weeks 96-104 |
88.858
(24.708)
|
83.543
(30.296)
|
| Title | Percentage of Hb Values 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 |
|---|---|
| Description | Percentage for each participant was calculated as 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 28-36, 44-52 and 96-104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Weeks 28-36 |
76.326
(28.175)
|
76.098
(28.991)
|
| Weeks 44-52 |
75.891
(31.047)
|
74.634
(30.589)
|
| Weeks 96-104 |
76.522
(30.378)
|
73.690
(33.040)
|
| Title | Number of Hospitalizations |
|---|---|
| Description | 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). It included all Non-Hemodialysis (HD) hospitalizations. The HD days were not counted as hospitalizations, even when performed overnight. |
| Time Frame | Baseline to End of Treatment (EOT) (Up to week 104) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS, with participants who had available data. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Mean (Standard Deviation) [Hospitalizations] |
0.9
(1.3)
|
0.9
(1.5)
|
| Title | Number of Days of Hospitalization Per Year |
|---|---|
| Description | The number of days of hospitalizations per year was calculated as the sum of the durations of all non-HD hospitalizations in days (Date of discharge - Date of admission + 1)] / (duration of efficacy emergent period in days / 365.25). In case of missing dates, the hospitalization duration was imputed by the average duration per stay derived from the participants with non-missing duration within the same treatment group. |
| Time Frame | Baseline to EOT (Up to week 104) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS, with participants who had available data. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Mean (Standard Deviation) [Days per year] |
12.186
(34.121)
|
7.868
(22.948)
|
| Title | Time to First Hospitalization |
|---|---|
| Description | 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. For participants without hospitalization, the time to censoring was calculated as: (Date of End of Efficacy Emergent Period - Analysis Date of first dose intake + 1) / 365.25. 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. |
| Time Frame | Baseline to EOT (Up to week 104) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Year 0.5 |
19.4
4.7%
|
18.3
4.3%
|
| Year 1 |
32.0
7.7%
|
32.7
7.8%
|
| Year 1.5 |
43.5
10.5%
|
41.9
10%
|
| Year 2 |
52.6
12.7%
|
48.3
11.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.164 |
| Comments | p-value for superiority test based on 2-sided significance level | |
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.154 | |
| Confidence Interval |
(2-Sided) 95% 0.943 to 1.411 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to First Use of Rescue Therapy |
|---|---|
| Description | Rescue therapy was defined as red blood cell (RBC) transfusion for both treatment groups and ESA for roxadustat participants. Only rescue medication that was started during the study treatment and up to end of efficacy emergent period was taken into account and considered as use of rescue medication. For participants who have experienced more than one use of rescue therapy, 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. |
| Time Frame | Baseline to EOT (Up to week 104) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Year 0.5 |
3.9
0.9%
|
3.2
0.8%
|
| Year 1 |
8.2
2%
|
8.4
2%
|
| Year 1.5 |
11.4
2.7%
|
10.9
2.6%
|
| Year 2 |
12.8
3.1%
|
14.4
3.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.917 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.979 | |
| Confidence Interval |
(2-Sided) 95% 0.656 to 1.462 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to First RBC Transfusion |
|---|---|
| Description | For participants who have experienced more than one RBC transfusion, only their first event following study treatment was used. For RBC transfusions, when the number of units was not given but the volume transfused was, the number of units were estimated by volume transfused/250 mL (for transfusion of packed cell units) or volume transfused/500 mL (for transfusion of full blood). Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. |
| Time Frame | Baseline to EOT (Up to week 104) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Year 0.5 |
3.6
0.9%
|
3.2
0.8%
|
| Year 1 |
7.4
1.8%
|
8.4
2%
|
| Year 1.5 |
10.0
2.4%
|
10.9
2.6%
|
| Year 2 |
11.4
2.7%
|
14.4
3.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment, and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.501 |
| Comments | p-value for superiority test based on 2-sided significance level | |
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.867 | |
| Confidence Interval |
(2-Sided) 95% 0.573 to 1.313 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Mean Monthly Number of RBC Packs Per Participant |
|---|---|
| Description | During efficacy emergent period, the mean monthly number of RBC packs was calculated as the sum of blood volume and units transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. Participants without medication records of RBC have their number of RBC packs and volume set to 0. |
| Time Frame | Baseline to EOT (Up to week 104) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Least Squares Mean (95% Confidence Interval) [RBC packs per month] |
0.026
|
0.032
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model included treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.507 |
| Comments | p-value for superiority test based on 2-sided significance level | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | -0.006 | |
| Confidence Interval |
(2-Sided) 95% -0.02 to 0.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Mean Monthly Volume of RBC Transfusion Per Participant |
|---|---|
| Description | During Efficacy Emergent Period, the mean monthly volume of blood transfused was calculated as the sum of blood volume and units transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Least Squares Mean (95% Confidence Interval) [mL per month] |
6.061
|
5.929
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model included treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.949 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.132 | |
| Confidence Interval |
(2-Sided) 95% -3.90 to 4.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to First Use of IV Iron Supplementation |
|---|---|
| Description | For participants who have 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. |
| Time Frame | Baseline to EOT (Up to week 104) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Year 0.5 |
11.2
2.7%
|
33.5
8%
|
| Year 1 |
17.4
4.2%
|
44.1
10.5%
|
| Year 1.5 |
23.6
5.7%
|
55.0
13.1%
|
| Year 2 |
33.3
8%
|
59.3
14.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.368 | |
| Confidence Interval |
(2-Sided) 95% 0.291 to 0.465 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Mean Monthly Intravenous (IV) Iron Per Participant During Weeks 37-52 and Weeks 53-104 |
|---|---|
| Description | Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg. |
| Time Frame | Weeks 37-52 and weeks 53-104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Weeks 37-52 |
34.9
|
70.0
|
| Weeks 53-104 |
49.5
|
98.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Weeks 37-52 - Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg. The model includes treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | -35.1 | |
| Confidence Interval |
(2-Sided) 95% -51.8 to -18.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | Weeks 53-104 - Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg. The model includes treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | -48.7 | |
| Confidence Interval |
(2-Sided) 95% -70.3 to -27.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Oral Iron Use Only |
|---|---|
| Description | Percentage of participants with/without IV iron only was calculated based on total number of participants within the Efficacy Emergent Period. The Efficacy Emergent Period is 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Number [Percentage of participants] |
31.0
7.5%
|
11.7
2.8%
|
| Title | Change From BL to Each Post-dosing Study Visit in Total Cholesterol |
|---|---|
| Description | Baseline assessment was the assessment from Day 1 visit. If baseline value was missing, then the latest screening period value was used as the baseline regardless of fasting status. |
| Time Frame | Baseline and weeks 8, 28, 52, 104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Change from BL to Week 8 |
-0.608
(0.889)
|
-0.105
(0.712)
|
| Change from BL to Week 28 |
-0.641
(0.960)
|
-0.135
(0.805)
|
| Change from BL to Week 52 |
-0.803
(1.027)
|
-0.241
(0.906)
|
| Change from BL to Week 104 |
-0.904
(1.053)
|
-0.277
(1.002)
|
| Title | Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Change from BL to Week 8 |
-0.245
(0.818)
|
-0.060
(0.726)
|
| Change from BL to Week 28 |
-0.155
(1.046)
|
-0.057
(0.922)
|
| Change from BL to Week 52 |
-0.345
(0.904)
|
-0.078
(0.886)
|
| Change from BL to Week 104 |
-0.261
(1.167)
|
-0.013
(1.048)
|
| Title | Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Change from BL to Week 8 |
-0.518
(0.823)
|
-0.107
(0.701)
|
| Change from BL to Week 28 |
-0.540
(0.907)
|
-0.127
(0.789)
|
| Change from BL to Week 52 |
-0.700
(0.965)
|
-0.229
(0.886)
|
| Change from BL to Week 104 |
-0.788
(1.024)
|
-0.240
(1.010)
|
| Title | Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Change from BL to Week 8 |
-0.114
(0.197)
|
-0.006
(0.172)
|
| Change from BL to Week 28 |
-0.113
(0.217)
|
-0.012
(0.193)
|
| Change from BL to Week 52 |
-0.097
(0.230)
|
-0.013
(0.195)
|
| Change from BL to Week 104 |
-0.097
(0.220)
|
-0.012
(0.196)
|
| Title | Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Change from BL to Week 8 |
-11.03
(18.49)
|
1.00
(14.34)
|
| Change from BL to Week 28 |
-11.18
(20.39)
|
-0.12
(16.91)
|
| Change from BL to Week 52 |
-13.18
(20.67)
|
-0.01
(18.88)
|
| Change from BL to Week 104 |
-13.50
(24.94)
|
-0.01
(20.00)
|
| Title | Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio |
|---|---|
| Description | 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. |
| Time Frame | Baseline and weeks 8, 28, 52, 104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Change from BL to Week 8 |
-0.037
(0.147)
|
0.013
(0.141)
|
| Change from BL to Week 28 |
-0.034
(0.177)
|
0.002
(0.148)
|
| Change from BL to Week 52 |
-0.051
(0.191)
|
0.007
(0.164)
|
| Change from BL to Week 104 |
-0.062
(0.210)
|
0.007
(0.201)
|
| Title | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 |
|---|---|
| Description | Missing category for Fasting Only includes non-fasting participants and the participants with missing values. |
| Time Frame | Weeks 12 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Yes [Regardless of Fasting Status] |
275
66.3%
|
231
54.9%
|
| No [Regardless of Fasting Status] |
119
28.7%
|
181
43%
|
| Missing [Regardless of Fasting Status] |
19
4.6%
|
8
1.9%
|
| Yes [Fasting Only] |
111
26.7%
|
85
20.2%
|
| No [Fasting Only] |
61
14.7%
|
80
19%
|
| Missing [Fasting Only] |
241
58.1%
|
255
60.6%
|
| Title | Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal |
|---|---|
| Description | Achieved antihypertensive treatment goal was defined as SBP < 140 mmHg and DBP < 90 mmHg over an evaluation period based on the average of available values in weeks 12-28 (pre-dialysis). |
| Time Frame | Weeks 12 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Antihypertensive Treatment Achievement - Yes |
264
63.6%
|
261
62%
|
| Antihypertensive Treatment Achievement - No |
130
31.3%
|
149
35.4%
|
| Antihypertensive Treatment Achievement-Missing |
19
4.6%
|
10
2.4%
|
| Title | Change From BL to the Average of Weeks 12 to 28 in SF-36 Physical Component Score (PCS) |
|---|---|
| Description | Baseline SF-36 PCS was defined as the SF-36 PCS value on Day 1. SF-36 contains 36-item that measures 8 scales with scores ranging from 0-100: physical functioning (PF); role limitations due to physical health problems (RP); bodily pain (BP); social functioning (SF); general health perceptions (GH); role limitations due to emotional problems (RE); vitality, energy or fatigue (VT); and mental health (MH). These scores are normed to the US population (norm-based scoring had very little impact on results when data was collected in Western European countries) to have a mean of 50 and standard deviation of 10. The PCS was calculated based on all 8 scales and ranges from 5.02-79.78. For each of these above scales, higher scores always indicating better health status. |
| Time Frame | Baseline and weeks 12 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 384 | 404 |
| Least Squares Mean (95% Confidence Interval) [Units on a scale] |
0.560
|
0.039
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model includes treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline SF-36 PCS, baseline Hb, as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.161 |
| Comments | p-value for superiority test based on 2-sided significance level | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.521 | |
| Confidence Interval |
(2-Sided) 95% -0.208 to 1.250 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From BL to the Average of Weeks 12 to 28 in Anemia Subscale (AnS) ("Additional Concerns") of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score |
|---|---|
| Description | 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 Anemia Subscale (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. For the above score, a higher score indicates better QoL. |
| Time Frame | Baseline and weeks 12 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 384 | 403 |
| Least Squares Mean (95% Confidence Interval) [Units on a scale] |
0.400
|
0.274
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model includes treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline FACT-An Ans, baseline Hb, as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.845 |
| Comments | p-value for superiority test based on 2-sided significance level | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 0.126 | |
| Confidence Interval |
(2-Sided) 95% -1.135 to 1.387 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From BL to the Average Value of Weeks 12 to 28 in Total FACT-An Score |
|---|---|
| Description | 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 (PWB) - 7 items, functional (FWB) - 7 items, social/family (SWB) - 7 items, and emotional (EWB) - 6 items. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia. The total score is obtained by summation of the scores from PWB, SWB, EWB, FWB and AnS. The FACT-An Total Score scale range is 0-188. A higher score indicates better QoL. |
| Time Frame | Baseline and weeks 12 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 383 | 403 |
| Least Squares Mean (95% Confidence Interval) [Units on a scale] |
-0.501
|
-0.373
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Roxadustat, ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Comments | The model includes treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline FACT-An Ans, baseline Hb, as continuous covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.922 |
| Comments | p-value for superiority test based on 2-sided significance level | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | -0.128 | |
| Confidence Interval |
(2-Sided) 95% -2.703 to 2.447 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From BL to the Average of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score |
|---|---|
| Description | Baseline assessment was defined as the value on Day 1. The EuroQol Questionnaire -5 Dimensions -5 Levels (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 visual analogue scale (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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 385 | 401 |
| Mean (Standard Deviation) [Units on a scale] |
3.041
(14.910)
|
2.735
(14.477)
|
| Title | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) |
|---|---|
| Description | The PGIC is a patient-rated instrument that measures 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 includes very much improved, much improved and minimally improved. |
| Time Frame | Baseline and weeks 8, 12, 28, 36, 52, 76, 104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Week 8 |
59.6
14.4%
|
49.5
11.8%
|
| Week 12 |
65.5
15.8%
|
49.5
11.8%
|
| Week 28 |
62.3
15%
|
57.1
13.6%
|
| Week 36 |
60.4
14.6%
|
56.3
13.4%
|
| Week 52 |
57.1
13.8%
|
55.3
13.1%
|
| Week 76 |
61.2
14.7%
|
51.9
12.3%
|
| Week 104 |
61.6
14.8%
|
51.3
12.2%
|
| Title | Change From BL in Serum Hepcidin |
|---|---|
| Description | 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, 12, 20, 36, 52, 104, and End of Study (EOS - up to 108 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS, with participants who had available data at baseline. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Week 4 |
-14.265
(42.393)
|
-4.265
(33.518)
|
| Week 12 |
-12.298
(41.335)
|
-6.741
(38.507)
|
| Week 20 |
-15.149
(43.152)
|
-11.818
(41.596)
|
| Week 36 |
-23.405
(43.033)
|
-14.530
(43.449)
|
| Week 52 |
-32.709
(42.342)
|
-17.522
(47.307)
|
| Week 104 |
-40.101
(48.611)
|
-18.735
(51.632)
|
| EOS |
-27.192
(52.169)
|
-17.664
(51.688)
|
| Title | Change From BL in Serum Ferritin |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 420 |
| Week 4 |
-214.64
(824.96)
|
-141.78
(456.15)
|
| Week 8 |
-245.37
(668.51)
|
-160.75
(607.39)
|
| Week 12 |
-269.76
(761.24)
|
-179.47
(586.95)
|
| Week 20 |
-337.94
(645.73)
|
-246.89
(727.64)
|
| Week 28 |
-427.46
(699.95)
|
-265.21
(816.64)
|
| Week 36 |
-507.34
(726.61)
|
-269.26
(855.01)
|
| Week 44 |
-545.14
(668.02)
|
-323.30
(986.38)
|
| Week 52 |
-615.19
(677.97)
|
-347.58
(1058.87)
|
| Week 60 |
-622.55
(675.22)
|
-394.40
(837.81)
|
| Week 68 |
-604.47
(773.19)
|
-456.16
(1039.18)
|
| Week 76 |
-646.76
(838.76)
|
-447.70
(967.63)
|
| Week 84 |
-629.31
(1060.24)
|
-454.44
(1193.43)
|
| Week 92 |
-749.58
(828.32)
|
-371.64
(1157.18)
|
| Week 100 |
-746.86
(796.74)
|
-364.78
(1802.37)
|
| Week 104 |
-753.82
(791.12)
|
-348.70
(1292.49)
|
| EOS |
-554.53
(910.01)
|
-166.94
(2035.26)
|
| Title | Change From BL in Transferrin Saturation (TSAT) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 412 | 420 |
| Week 4 |
-4.151
(16.147)
|
-2.331
(13.178)
|
| Week 8 |
-3.681
(17.062)
|
-3.128
(14.461)
|
| Week 12 |
-2.643
(17.551)
|
-3.189
(13.912)
|
| Week 20 |
-3.782
(16.634)
|
-4.398
(14.444)
|
| Week 28 |
-5.463
(17.798)
|
-3.829
(15.216)
|
| Week 36 |
-5.351
(17.803)
|
-4.022
(15.471)
|
| Week 44 |
-6.069
(16.349)
|
-5.254
(15.144)
|
| Week 52 |
-7.278
(17.244)
|
-5.788
(14.666)
|
| Week 60 |
-6.997
(16.774)
|
-5.187
(16.097)
|
| Week 68 |
-7.279
(17.809)
|
-6.237
(15.934)
|
| Week 76 |
-7.156
(17.682)
|
-6.623
(16.395)
|
| Week 84 |
-7.867
(17.654)
|
-5.378
(17.771)
|
| Week 92 |
-6.996
(19.850)
|
-6.259
(16.605)
|
| Week 100 |
-8.379
(17.809)
|
-6.354
(17.147)
|
| Week 104 |
-7.650
(17.842)
|
-5.054
(17.195)
|
| EOS |
-5.466
(16.626)
|
-3.763
(17.813)
|
| Title | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) |
|---|---|
| Description | 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, 52, 60, 84, 104 and EOS (up to 108 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the FAS, with participants who had available data at baseline. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 413 | 419 |
| Week 12 |
0.0009
(0.0071)
|
-0.0005
(0.0057)
|
| Week 28 |
-0.0004
(0.0067)
|
-0.0006
(0.0064)
|
| Week 36 |
-0.0001
(0.0065)
|
-0.0004
(0.0067)
|
| Week 44 |
-0.0001
(0.0069)
|
-0.0006
(0.0067)
|
| Week 52 |
-0.0001
(0.0070)
|
-0.0007
(0.0068)
|
| Week 60 |
0.0000
(0.0080)
|
-0.0004
(0.0070)
|
| Week 84 |
0.0003
(0.0072)
|
0.0001
(0.0078)
|
| Week 104 |
0.0000
(0.0075)
|
-0.0003
(0.0082)
|
| EOS |
0.0011
(0.0076)
|
0.0001
(0.0080)
|
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
|---|---|
| Description | Safety was assessed by evaluation of the following variables: (TEAEs; frequency, severity, seriousness, and relationship to study drug), Vital signs (systolic and diastolic blood pressure, pulse, respiratory rate and weight), Clinical laboratory variables (hematology, biochemistry including liver enzymes and total bilirubin, and urinalysis), Physical examination, 12-lead electrocardiogram (ECG) and Vascular Access Thrombosis. All AEs collected during the Safety Emergent Period were counted as TEAE. The TEAE was defined as an adverse event (AE) if it was observed after starting administration of the roxadustat or ESA. Any clinically significant abnormalities were reported as an AEs. All reported deaths after the first study drug administration and up to 28 days after the Analysis Date of Last Dose and considering last dosing frequency. |
| Time Frame | Baseline up to EOS (Up to week 108) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was the Safety Analysis Set (SAF) which consisted of all randomized participants who received at least one dose of study drug. |
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. |
| Measure Participants | 414 | 420 |
| TEAE |
359
86.5%
|
361
85.7%
|
| Drug-Related TEAE |
77
18.6%
|
35
8.3%
|
| Serious TEAE |
210
50.6%
|
189
44.9%
|
| Drug-Related Serious TEAE |
33
8%
|
10
2.4%
|
| TEAE Leading to Death |
67
16.1%
|
55
13.1%
|
| Drug-Related TEAE Leading to Death |
5
1.2%
|
2
0.5%
|
| TEAE Leading to Withdrawal of Treatment |
35
8.4%
|
16
3.8%
|
| Drug-Related TEAE Leading to Withdraw of Treatment |
9
2.2%
|
1
0.2%
|
| TEAE NCI CTC Grades 3 or Higher |
181
43.6%
|
149
35.4%
|
| Death During the Safety Emergent Period |
64
15.4%
|
51
12.1%
|
| Death |
78
18.8%
|
59
14%
|
Adverse Events
| Time Frame | From first dose of study drug up to End of Study (EOS) (Up to week 108) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||
| Arm/Group Title | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) | ||
| Arm/Group Description | Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. | ||
All Cause Mortality |
||||
| Roxadustat | ESA (Erythropoiesis-Stimulating Agent) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 78/414 (18.8%) | 59/420 (14%) | ||
Serious Adverse Events |
||||
| Roxadustat | ESA (Erythropoiesis-Stimulating Agent) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 210/414 (50.7%) | 189/420 (45%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 5/414 (1.2%) | 5 | 7/420 (1.7%) | 8 |
| Hypocoagulable state | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Cardiac disorders | ||||
| Acute coronary syndrome | 3/414 (0.7%) | 3 | 3/420 (0.7%) | 3 |
| Acute left ventricular failure | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Acute myocardial infarction | 9/414 (2.2%) | 9 | 11/420 (2.6%) | 13 |
| Angina pectoris | 5/414 (1.2%) | 5 | 6/420 (1.4%) | 8 |
| Angina unstable | 0/414 (0%) | 0 | 2/420 (0.5%) | 4 |
| Aortic valve stenosis | 2/414 (0.5%) | 2 | 1/420 (0.2%) | 1 |
| Arrhythmia | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Arteriosclerosis coronary artery | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Atrial fibrillation | 12/414 (2.9%) | 14 | 8/420 (1.9%) | 8 |
| Atrial flutter | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Atrial tachycardia | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Atrioventricular block | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Atrioventricular block complete | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Atrioventricular block second degree | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Bradycardia | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Cardiac arrest | 4/414 (1%) | 4 | 8/420 (1.9%) | 9 |
| Cardiac failure | 8/414 (1.9%) | 8 | 9/420 (2.1%) | 9 |
| Cardiac failure acute | 3/414 (0.7%) | 3 | 1/420 (0.2%) | 1 |
| Cardiac failure chronic | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Cardiac failure congestive | 5/414 (1.2%) | 5 | 1/420 (0.2%) | 1 |
| Cardiac fibrillation | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Cardio-respiratory arrest | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 3 |
| Cardiogenic shock | 2/414 (0.5%) | 2 | 1/420 (0.2%) | 1 |
| Cardiopulmonary failure | 3/414 (0.7%) | 3 | 1/420 (0.2%) | 1 |
| Cardiovascular insufficiency | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Coronary artery disease | 2/414 (0.5%) | 2 | 3/420 (0.7%) | 3 |
| Coronary artery occlusion | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Coronary artery stenosis | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Diastolic dysfunction | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Hypertensive heart disease | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Left ventricular failure | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Mitral valve incompetence | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Mitral valve stenosis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Myocardial infarction | 1/414 (0.2%) | 1 | 6/420 (1.4%) | 6 |
| Myocardial ischaemia | 4/414 (1%) | 5 | 4/420 (1%) | 4 |
| Pericarditis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Sinus node dysfunction | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Supraventricular tachycardia | 1/414 (0.2%) | 1 | 5/420 (1.2%) | 5 |
| Tachyarrhythmia | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Tricuspid valve incompetence | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Ventricular arrhythmia | 0/414 (0%) | 0 | 1/420 (0.2%) | 2 |
| Ventricular fibrillation | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Ear and labyrinth disorders | ||||
| Hypoacusis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Vertigo | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Endocrine disorders | ||||
| Hyperparathyroidism secondary | 3/414 (0.7%) | 3 | 0/420 (0%) | 0 |
| Hyperthyroidism | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Toxic goitre | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Eye disorders | ||||
| Angle closure glaucoma | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Cataract | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Eye haemorrhage | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal adhesions | 0/414 (0%) | 0 | 1/420 (0.2%) | 2 |
| Abdominal pain | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Abdominal wall haematoma | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Acute abdomen | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Anal fissure | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Anal fistula | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Anal incontinence | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Chronic gastritis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Colitis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Colitis ischaemic | 0/414 (0%) | 0 | 1/420 (0.2%) | 2 |
| Constipation | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 3 |
| Diarrhoea | 2/414 (0.5%) | 2 | 3/420 (0.7%) | 4 |
| Diverticulum | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Diverticulum intestinal | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Duodenal ulcer | 4/414 (1%) | 4 | 0/420 (0%) | 0 |
| Erosive duodenitis | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Faecaloma | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Gastric ulcer | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Gastritis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Gastritis erosive | 2/414 (0.5%) | 2 | 2/420 (0.5%) | 2 |
| Gastrointestinal haemorrhage | 0/414 (0%) | 0 | 6/420 (1.4%) | 6 |
| Gastrointestinal ischaemia | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Gastrointestinal necrosis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Haemorrhoids | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Ileus paralytic | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Intestinal ischaemia | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Intestinal obstruction | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Intestinal ulcer perforation | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Intra-abdominal haematoma | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Large intestinal haemorrhage | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Large intestine perforation | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Mechanical ileus | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Melaena | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Nausea | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Oesophageal ulcer | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Oesophagitis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Pancreatitis acute | 0/414 (0%) | 0 | 3/420 (0.7%) | 3 |
| Ulcerative gastritis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 2/414 (0.5%) | 3 | 1/420 (0.2%) | 1 |
| Vomiting | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| General disorders | ||||
| Asthenia | 3/414 (0.7%) | 3 | 1/420 (0.2%) | 1 |
| Catheter site haematoma | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Catheter site inflammation | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Chest pain | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Chills | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Complication associated with device | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Death | 6/414 (1.4%) | 6 | 3/420 (0.7%) | 3 |
| Device related thrombosis | 3/414 (0.7%) | 5 | 1/420 (0.2%) | 1 |
| Hyperthermia | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Impaired healing | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Malaise | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Medical device site phlebitis | 1/414 (0.2%) | 2 | 0/420 (0%) | 0 |
| Multiple organ dysfunction syndrome | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Oedema peripheral | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Pain | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Peripheral swelling | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Pyrexia | 4/414 (1%) | 4 | 4/420 (1%) | 5 |
| Sudden cardiac death | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Sudden death | 7/414 (1.7%) | 7 | 3/420 (0.7%) | 3 |
| Vascular stent stenosis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Hepatobiliary disorders | ||||
| Bile duct obstruction | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Bile duct stone | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Cholangitis | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Cholecystitis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Cholecystitis acute | 1/414 (0.2%) | 1 | 3/420 (0.7%) | 3 |
| Hepatotoxicity | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Hyperbilirubinaemia | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Jaundice | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Immune system disorders | ||||
| Anti-neutrophil cytoplasmic antibody positive vasculitis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Renal transplant failure | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Infections and infestations | ||||
| Abdominal abscess | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Abdominal infection | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Abscess neck | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Acute hepatitis B | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Appendicitis | 2/414 (0.5%) | 2 | 1/420 (0.2%) | 1 |
| Arteriovenous fistula site infection | 3/414 (0.7%) | 3 | 0/420 (0%) | 0 |
| Arthritis bacterial | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Bacterial sepsis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Biliary sepsis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Bronchitis | 5/414 (1.2%) | 5 | 3/420 (0.7%) | 3 |
| Cellulitis | 2/414 (0.5%) | 2 | 1/420 (0.2%) | 1 |
| Cholecystitis infective | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Clostridium difficile infection | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Device related infection | 2/414 (0.5%) | 2 | 3/420 (0.7%) | 4 |
| Device related sepsis | 3/414 (0.7%) | 3 | 3/420 (0.7%) | 3 |
| Diabetic gangrene | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Diverticulitis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Encephalomyelitis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Endocarditis | 2/414 (0.5%) | 3 | 0/420 (0%) | 0 |
| Enterobacter bacteraemia | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Enterococcal sepsis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Erysipelas | 1/414 (0.2%) | 1 | 3/420 (0.7%) | 3 |
| Escherichia bacteraemia | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Escherichia urinary tract infection | 1/414 (0.2%) | 2 | 1/420 (0.2%) | 1 |
| Fungal oesophagitis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Gangrene | 5/414 (1.2%) | 6 | 4/420 (1%) | 7 |
| Gastric ulcer helicobacter | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Gastroenteritis | 0/414 (0%) | 0 | 6/420 (1.4%) | 6 |
| Gastrointestinal candidiasis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Haematoma infection | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Incision site infection | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Infected skin ulcer | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Infectious colitis | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Influenza | 2/414 (0.5%) | 2 | 1/420 (0.2%) | 1 |
| Intervertebral discitis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Liver abscess | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Localised infection | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Lower respiratory tract infection | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Lung abscess | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Medical device site joint infection | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Osteomyelitis | 1/414 (0.2%) | 2 | 0/420 (0%) | 0 |
| Osteomyelitis bacterial | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Pancreatitis bacterial | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Penile abscess | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Periodontitis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Peritonitis | 10/414 (2.4%) | 15 | 3/420 (0.7%) | 4 |
| Peritonitis bacterial | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Pneumonia | 15/414 (3.6%) | 15 | 21/420 (5%) | 22 |
| Pneumonia pneumococcal | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Postoperative wound infection | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Pseudomonal sepsis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Pyelonephritis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Pyelonephritis acute | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Pyelonephritis chronic | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Pyonephrosis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Renal abscess | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Renal cyst infection | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Respiratory tract infection | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Respiratory tract infection bacterial | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Sepsis | 8/414 (1.9%) | 8 | 9/420 (2.1%) | 9 |
| Sepsis syndrome | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Septic shock | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Sinusitis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Skin infection | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Soft tissue infection | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Staphylococcal bacteraemia | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Staphylococcal sepsis | 3/414 (0.7%) | 3 | 2/420 (0.5%) | 2 |
| Streptococcal sepsis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Subcutaneous abscess | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Systemic infection | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Tracheobronchitis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Upper respiratory tract infection | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Urinary tract infection | 4/414 (1%) | 4 | 0/420 (0%) | 0 |
| Urinary tract infection bacterial | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Urinary tract infection enterococcal | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Urinary tract infection pseudomonal | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Urinary tract infection staphylococcal | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Urosepsis | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Viral upper respiratory tract infection | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Ankle fracture | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Arteriovenous fistula aneurysm | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Arteriovenous fistula occlusion | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Arteriovenous fistula site complication | 6/414 (1.4%) | 7 | 5/420 (1.2%) | 5 |
| Arteriovenous fistula site haemorrhage | 2/414 (0.5%) | 3 | 1/420 (0.2%) | 1 |
| Arteriovenous fistula thrombosis | 29/414 (7%) | 37 | 15/420 (3.6%) | 18 |
| Arteriovenous graft site haemorrhage | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Arteriovenous graft site stenosis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Arteriovenous graft thrombosis | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 5 |
| Back injury | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Comminuted fracture | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Concussion | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Facial bones fracture | 0/414 (0%) | 0 | 1/420 (0.2%) | 2 |
| Fall | 0/414 (0%) | 0 | 6/420 (1.4%) | 6 |
| Femoral neck fracture | 2/414 (0.5%) | 2 | 1/420 (0.2%) | 1 |
| Femur fracture | 2/414 (0.5%) | 2 | 5/420 (1.2%) | 5 |
| Graft thrombosis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Head injury | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Hip fracture | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Ligament rupture | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Limb injury | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Lip injury | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Lower limb fracture | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Lumbar vertebral fracture | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Poisoning | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Post procedural haematoma | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Post procedural haemorrhage | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Post procedural inflammation | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Procedural complication | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Pubis fracture | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Radius fracture | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Rib fracture | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Shunt aneurysm | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Shunt malfunction | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Shunt occlusion | 2/414 (0.5%) | 5 | 1/420 (0.2%) | 1 |
| Shunt stenosis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Shunt thrombosis | 1/414 (0.2%) | 1 | 4/420 (1%) | 5 |
| Skin injury | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Skin wound | 1/414 (0.2%) | 2 | 0/420 (0%) | 0 |
| Spinal compression fracture | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Spinal fracture | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Subdural haematoma | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Thermal burn | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Thoracic vertebral fracture | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Tibia fracture | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Ulna fracture | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Upper limb fracture | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Vascular access malfunction | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Vascular access site haemorrhage | 0/414 (0%) | 0 | 1/420 (0.2%) | 2 |
| Vascular pseudoaneurysm | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Wound | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Investigations | ||||
| Blood potassium increased | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Electrocardiogram abnormal | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Metabolism and nutrition disorders | ||||
| Cachexia | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Dehydration | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Diabetes mellitus | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Diabetes mellitus inadequate control | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Fluid overload | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 3 |
| Fluid retention | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Hypercalcaemia | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Hyperglycaemia | 2/414 (0.5%) | 3 | 0/420 (0%) | 0 |
| Hyperkalaemia | 4/414 (1%) | 4 | 3/420 (0.7%) | 3 |
| Hypervolaemia | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Hypoglycaemia | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Metabolic acidosis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Fistula discharge | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Joint contracture | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Mobility decreased | 0/414 (0%) | 0 | 1/420 (0.2%) | 2 |
| Musculoskeletal chest pain | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Osteitis | 0/414 (0%) | 0 | 1/420 (0.2%) | 2 |
| Osteoarthritis | 2/414 (0.5%) | 2 | 1/420 (0.2%) | 1 |
| Osteonecrosis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Rotator cuff syndrome | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Sarcopenia | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute myeloid leukaemia | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Adenocarcinoma gastric | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Adenocarcinoma of colon | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Basal cell carcinoma | 2/414 (0.5%) | 3 | 2/420 (0.5%) | 2 |
| Benign lung neoplasm | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Benign renal neoplasm | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Bladder cancer | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Bowen's disease | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Carcinoid tumour pulmonary | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Colon adenoma | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Colon cancer | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Colorectal adenocarcinoma | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Colorectal cancer metastatic | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Endometrial adenocarcinoma | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Haemangioma of bone | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Hypopharyngeal neoplasm | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Invasive ductal breast carcinoma | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Kidney angiomyolipoma | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Lung neoplasm | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Lung neoplasm malignant | 3/414 (0.7%) | 3 | 2/420 (0.5%) | 2 |
| Malignant neoplasm of choroid | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Metastases to central nervous system | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Metastases to liver | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Metastatic neoplasm | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Myelodysplastic syndrome | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Ovarian neoplasm | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Papillary thyroid cancer | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Parathyroid tumour benign | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Penile cancer | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Prostate cancer | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Refractory anaemia with an excess of blasts | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Renal cell carcinoma | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Skin cancer | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Small cell lung cancer | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Squamous cell carcinoma of lung | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Squamous cell carcinoma of skin | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Nervous system disorders | ||||
| Carotid artery stenosis | 0/414 (0%) | 0 | 1/420 (0.2%) | 2 |
| Carpal tunnel syndrome | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Cerebellar infarction | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Cerebral arteriosclerosis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Cerebral artery occlusion | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Cerebral haemorrhage | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Cerebral infarction | 0/414 (0%) | 0 | 4/420 (1%) | 5 |
| Cerebral ischaemia | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Cerebrovascular accident | 3/414 (0.7%) | 3 | 1/420 (0.2%) | 1 |
| Cerebrovascular disorder | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Cognitive disorder | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Coma | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Disturbance in attention | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Dizziness | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Embolic cerebral infarction | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Encephalopathy | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Epilepsy | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Epileptic encephalopathy | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Generalised tonic-clonic seizure | 1/414 (0.2%) | 2 | 0/420 (0%) | 0 |
| Haemorrhage intracranial | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Haemorrhagic stroke | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Hypoxic-ischaemic encephalopathy | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Idiopathic partial epilepsy | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Ischaemic stroke | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Lethargy | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Loss of consciousness | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Seizure | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Syncope | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Transient ischaemic attack | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Vascular dementia | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Vertigo CNS origin | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Product Issues | ||||
| Device dislocation | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Device failure | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Device malfunction | 4/414 (1%) | 5 | 0/420 (0%) | 0 |
| Psychiatric disorders | ||||
| Confusional state | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Delirium | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Depression | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Disorientation | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Fear of falling | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Mental disorder due to a general medical condition | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Organic brain syndrome | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Renal and urinary disorders | ||||
| Calculus urinary | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Chronic kidney disease | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| End stage renal disease | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Haematuria | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Hydronephrosis | 0/414 (0%) | 0 | 2/420 (0.5%) | 3 |
| Renal cyst ruptured | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Tubulointerstitial nephritis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Urethral perforation | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Urinary retention | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Urinoma | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Ovarian disorder | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Uterine polyp | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Vaginal haemorrhage | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Acute respiratory distress syndrome | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Acute respiratory failure | 2/414 (0.5%) | 2 | 2/420 (0.5%) | 2 |
| Atelectasis | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Bronchitis chronic | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 2 |
| Chronic obstructive pulmonary disease | 2/414 (0.5%) | 2 | 1/420 (0.2%) | 1 |
| Chronic respiratory failure | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Dyspnoea | 4/414 (1%) | 4 | 4/420 (1%) | 4 |
| Eosinophilic pneumonia | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Haemoptysis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Interstitial lung disease | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Pleural effusion | 6/414 (1.4%) | 7 | 2/420 (0.5%) | 3 |
| Pleural thickening | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Pleurisy | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Pneumonia aspiration | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Pulmonary alveolar haemorrhage | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Pulmonary embolism | 4/414 (1%) | 4 | 1/420 (0.2%) | 1 |
| Pulmonary hypertension | 2/414 (0.5%) | 2 | 1/420 (0.2%) | 1 |
| Pulmonary infarction | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Pulmonary oedema | 6/414 (1.4%) | 6 | 2/420 (0.5%) | 2 |
| Respiratory arrest | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Respiratory failure | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Cutaneous vasculitis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Diabetic foot | 0/414 (0%) | 0 | 2/420 (0.5%) | 2 |
| Ingrowing nail | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Neurodermatitis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Rash vesicular | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Skin lesion | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Skin necrosis | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Skin ulcer | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Toxic epidermal necrolysis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Urticaria | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Surgical and medical procedures | ||||
| Catheter placement | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Therapy cessation | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Vascular disorders | ||||
| Aortic dissection | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Aortic stenosis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Arterial disorder | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Circulatory collapse | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Deep vein thrombosis | 4/414 (1%) | 5 | 0/420 (0%) | 0 |
| Diabetic vascular disorder | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Dry gangrene | 1/414 (0.2%) | 1 | 2/420 (0.5%) | 3 |
| Haematoma | 0/414 (0%) | 0 | 3/420 (0.7%) | 3 |
| Haemorrhage | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Hypertension | 10/414 (2.4%) | 10 | 5/420 (1.2%) | 5 |
| Hypertensive crisis | 3/414 (0.7%) | 4 | 3/420 (0.7%) | 8 |
| Hypotension | 4/414 (1%) | 5 | 1/420 (0.2%) | 3 |
| Intermittent claudication | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Lymphoedema | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Malignant hypertension | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Orthostatic hypotension | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Peripheral arterial occlusive disease | 2/414 (0.5%) | 2 | 4/420 (1%) | 4 |
| Peripheral artery occlusion | 0/414 (0%) | 0 | 3/420 (0.7%) | 3 |
| Peripheral artery stenosis | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Peripheral artery thrombosis | 2/414 (0.5%) | 2 | 0/420 (0%) | 0 |
| Peripheral ischaemia | 2/414 (0.5%) | 2 | 4/420 (1%) | 6 |
| Peripheral vascular disorder | 0/414 (0%) | 0 | 1/420 (0.2%) | 1 |
| Steal syndrome | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Subclavian artery thrombosis | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 1 |
| Subclavian vein thrombosis | 1/414 (0.2%) | 1 | 0/420 (0%) | 0 |
| Thrombosis | 1/414 (0.2%) | 2 | 1/420 (0.2%) | 1 |
| Vasculitis necrotising | 0/414 (0%) | 0 | 1/420 (0.2%) | 2 |
| Venous stenosis | 1/414 (0.2%) | 1 | 1/420 (0.2%) | 5 |
Other (Not Including Serious) Adverse Events |
||||
| Roxadustat | ESA (Erythropoiesis-Stimulating Agent) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 210/414 (50.7%) | 209/420 (49.8%) | ||
| Endocrine disorders | ||||
| Hyperparathyroidism secondary | 21/414 (5.1%) | 21 | 16/420 (3.8%) | 17 |
| Gastrointestinal disorders | ||||
| Diarrhoea | 33/414 (8%) | 51 | 32/420 (7.6%) | 60 |
| Nausea | 27/414 (6.5%) | 29 | 8/420 (1.9%) | 10 |
| Infections and infestations | ||||
| Bronchitis | 29/414 (7%) | 38 | 27/420 (6.4%) | 34 |
| Upper respiratory tract infection | 14/414 (3.4%) | 19 | 21/420 (5%) | 29 |
| Viral upper respiratory tract infection | 28/414 (6.8%) | 61 | 39/420 (9.3%) | 68 |
| Injury, poisoning and procedural complications | ||||
| Arteriovenous fistula thrombosis | 27/414 (6.5%) | 34 | 18/420 (4.3%) | 21 |
| Metabolism and nutrition disorders | ||||
| Iron deficiency | 30/414 (7.2%) | 39 | 51/420 (12.1%) | 64 |
| Musculoskeletal and connective tissue disorders | ||||
| Muscle spasms | 15/414 (3.6%) | 21 | 33/420 (7.9%) | 48 |
| Nervous system disorders | ||||
| Headache | 36/414 (8.7%) | 41 | 29/420 (6.9%) | 39 |
| Vascular disorders | ||||
| Hypertension | 66/414 (15.9%) | 101 | 75/420 (17.9%) | 116 |
| Hypotension | 30/414 (7.2%) | 40 | 26/420 (6.2%) | 40 |
Limitations/Caveats
Overall 838 were randomized to receive treatment. Two participants randomized to the pooled ESA treatment group were excluded due to GCP violations and their data was excluded. Total of 836 were considered randomized.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Results Point of Contact
| Name/Title | Clinical Trial Disclosure |
|---|---|
| Organization | Astellas Pharma Europe B.V. |
| Phone | 800-888-7704 ext 5473 |
| astellas.resultsdisclosure@astellas.com |
Responsible Party:
Astellas Pharma Europe B.V.
ClinicalTrials.gov Identifier:
NCT02278341
Other Study ID Numbers:
- 1517-CL-0613
- 2013-001497-16
First Posted:
Oct 30, 2014
Last Update Posted:
Feb 4, 2021
Last Verified:
Dec 1, 2020