Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Change From Baseline (BL) to the Average Hemoglobin (Hb) in Weeks 28-36 Without Rescue Therapy [EU (EMA)] |
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. |
Baseline and weeks 28 to 36 |
|
| Primary |
Change From BL to the Average Hb in Weeks 28 to 52 Regardless of Rescue Therapy [US (FDA)] |
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. |
Baseline and weeks 28 to 52 |
|
| Secondary |
Percentage of Participants With Hb Response During 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). |
Weeks 28 to 36 |
|
| Secondary |
Change From BL in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of 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. |
Baseline and weeks 12 to 28 |
|
| Secondary |
Mean Monthly Intravenous (IV) Iron Use |
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. |
Day 1 to week 36 |
|
| Secondary |
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 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. |
Baseline and weeks 12 to 28 |
|
| Secondary |
Change From BL in SF-36 Vitality (VT) Sub-score to the Average of 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. |
Baseline and weeks 12 to 28 |
|
| Secondary |
Change From BL in Mean Arterial Pressure (MAP) to the Average of 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. |
Baseline and weeks 20 to 28 |
|
| Secondary |
Time to First Occurrence of an Increase in Blood Pressure |
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. |
Weeks 1 to 36 |
|
| Secondary |
Change From BL in Mean Arterial Pressure (MAP) to the Average MAP Value of 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. |
Baseline and weeks 20 to 28 |
|
| Secondary |
Time to First Occurrence of an Increase in Blood Pressure |
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. |
Weeks 1 to 36 |
|
| Secondary |
Percentage of Participants With a Hb Response During Weeks 28 and 36 Regardless of Use of Rescue Therapy |
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. |
Weeks 28 to 36 |
|
| Secondary |
Change From BL in Hb to Each Postdosing Time Point |
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). |
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 |
|
| Secondary |
Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy |
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. |
Weeks 28 to 36, 44 to 52, and 96 to 104 |
|
| Secondary |
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 |
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). |
Baseline and weeks 28 to 36, 44 to 52, and 96 to 104 |
|
| Secondary |
Percentage of Hb Values = 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy |
Percentage for each participant was calculated 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. |
Weeks 28-36, 44-52 and 96-104 |
|
| Secondary |
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 |
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. |
Weeks 28-36, 44-52 and 96-104 |
|
| Secondary |
Number of Hospitalizations |
The number of hospitalizations per participant were calculated during the Efficacy Emergent Period. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). It included all Non-Hemodialysis (HD) hospitalizations. The HD days were not counted as hospitalizations, even when performed overnight. |
Baseline to End of Treatment (EOT) (Up to week 104) |
|
| Secondary |
Number of Days of Hospitalization Per Year |
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. |
Baseline to EOT (Up to week 104) |
|
| Secondary |
Time to First Hospitalization |
Time to first hospitalization in years was defined in years as: (First event date during the Efficacy Emergent Period - Analysis date of First dose intake +1)/365.25, and the 'First event date' was defined as 'Date of first Admission and 'Analysis Date of first dose intake. 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. |
Baseline to EOT (Up to week 104) |
|
| Secondary |
Time to First Use of Rescue Therapy |
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. |
Baseline to EOT (Up to week 104) |
|
| Secondary |
Time to First RBC Transfusion |
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. |
Baseline to EOT (Up to week 104) |
|
| Secondary |
Mean Monthly Number of RBC Packs Per Participant |
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. |
Baseline to EOT (Up to week 104) |
|
| Secondary |
Mean Monthly Volume of RBC Transfusion Per Participant |
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). |
Baseline to EOT (Up to week 104) |
|
| Secondary |
Time to First Use of IV Iron Supplementation |
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. |
Baseline to EOT (Up to week 104) |
|
| Secondary |
Mean Monthly Intravenous (IV) Iron Per Participant During 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. |
Weeks 37-52 and weeks 53-104 |
|
| Secondary |
Percentage of Participants With Oral Iron Use Only |
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). |
Baseline to EOT (Up to week 104) |
|
| Secondary |
Change From BL to Each Post-dosing Study Visit in Total Cholesterol |
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. |
Baseline and weeks 8, 28, 52, 104 |
|
| Secondary |
Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio |
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
Baseline and weeks 8, 28, 52, 104 |
|
| Secondary |
Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol |
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
Baseline and weeks 8, 28, 52, 104 |
|
| Secondary |
Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) |
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
Baseline and weeks 8, 28, 52, 104 |
|
| Secondary |
Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) |
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
Baseline and weeks 8, 28, 52, 104 |
|
| Secondary |
Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio |
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used. |
Baseline and weeks 8, 28, 52, 104 |
|
| Secondary |
Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 |
Missing category for Fasting Only includes non-fasting participants and the participants with missing values. |
Weeks 12 to 28 |
|
| Secondary |
Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal |
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). |
Weeks 12 to 28 |
|
| Secondary |
Change From BL to the Average of Weeks 12 to 28 in SF-36 Physical Component Score (PCS) |
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. |
Baseline and weeks 12 to 28 |
|
| Secondary |
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 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. |
Baseline and weeks 12 to 28 |
|
| Secondary |
Change From BL to the Average Value of Weeks 12 to 28 in Total FACT-An Score |
Baseline FACT-An Total Score was defined on Day 1. Total Fact-An score is composed of FACT-G and Ans scales. FACT-G contains 27 items that cover four dimensions of well-being: physical (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. |
Baseline and weeks 12 to 28 |
|
| Secondary |
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 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. |
Baseline and weeks 12 to 28 |
|
| Secondary |
Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) |
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. |
Baseline and weeks 8, 12, 28, 36, 52, 76, 104 |
|
| Secondary |
Change From BL in Serum Hepcidin |
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. |
Baseline and weeks 4, 12, 20, 36, 52, 104, and End of Study (EOS - up to 108 weeks) |
|
| Secondary |
Change From BL in Serum Ferritin |
Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104, and EOS (up to 108 weeks) |
|
| Secondary |
Change From BL in Transferrin Saturation (TSAT) |
Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 and EOS (up to 108 weeks) |
|
| Secondary |
Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) |
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. |
Baseline and weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to 108 weeks) |
|
| Secondary |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
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. |
Baseline up to EOS (Up to week 108) |
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