Anemia in Chronic Kidney Disease in Non-dialysis Patients
Conditions
Keywords
anemia, chronic kidney disease (CKD), Hemoglobin (Hb), non-dialysis
Brief summary
This study was conducted to treat anemia in patients with chronic kidney disease. Anemia is a reduced number of red blood cells or hemoglobin. Hemoglobin is important for the transport of oxygen in your blood. The purpose of the study was to see if Roxadustat is both effective and safe as a treatment for anemia in patients with chronic kidney disease.
Detailed description
The study consisted of three study periods as follows: * Screening period: up to 6 weeks * Treatment period: minimum 52 weeks (primary treatment period) up to a maximum of 104 weeks (extended treatment period) * Post-Treatment Follow-Up period: 4 weeks
Interventions
DRUGRoxadustat
Roxadustat was administered initially according to the tiered weight-based dosing, where participants with weight from ≥ 45 to ≤ 70 kg received 70 mg and participants with \> 70 to ≤ 160 kg received 100 mg of roxadustat. Dose-titration based upon regular measurement of Hb levels was performed until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL.
DRUGPlacebo
Placebo was administered initially according to the tiered weight-based dosing, where participants with weight from ≥ 45 to ≤ 70 kg received 70 mg and participants with \> 70 to ≤ 160 kg received 100 mg of roxadustat. Dose-titration based upon regular measurement of Hb levels was performed until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL.
Sponsors
Kyntra Bio
Astellas Pharma Europe B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant has a diagnosis of chronic kidney disease, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4 or 5, not receiving dialysis; with an Estimated Glomerular Filtration Rate (eGFR) \<60 mL/min/1.73 m\^2 estimated using the abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) equation. * The mean of the Participant's three most recent Hb values during the Screening period, obtained at least 4 days apart, must be less than or equal to 10.0 g/dL, with a difference of less than or equal to 1.0 g/dL between the highest and the lowest values. The last Hb value must be within 10 days prior to randomization. * Participant has a ferritin level greater than or equal to 30 ng/mL (greater than or equal to 67.4 pmol/L) at screening. * Participant has a transferrin saturation (TSAT) level greater than or equal to 5% at screening. * Participant has a serum folate level greater than or equal to lower limit of normal at screening. * Participant has a serum vitamin B12 level greater than or equal to lower limit of normal at screening. * Participant's alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels are less than or equal to 3 x upper limit of normal (ULN), and total bilirubin (TBL) is less than or equal to 1.5 x ULN. * Participant's body weight is 45.0 kg up to a maximum of 160.0 kg.
Exclusion criteria
* Participant has received any ESA treatment within 12 weeks prior to randomization. * Participant has had more than one dose of IV iron within 12 weeks prior to randomization. * Participant has received a RBC transfusion within 8 weeks prior to randomization. * Participant has a known history of myelodysplastic syndrome or multiple myeloma. * 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 CKD. * Participant has a known hemosiderosis, hemochromatosis, coagulation disorder, or hypercoagulable condition. * Participant has chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission. * Participant is anticipated to have elective surgery that is expected to lead to significant blood loss or anticipated elective coronary revascularization. * Participant has active or chronic gastrointestinal bleeding. * Participant has received any prior treatment with roxadustat or a hypoxia-inducible factor Prolyl Hydroxylase Inhibitor (HIF-PHI). * Participant has been treated with iron-chelating agents within 4 weeks prior to randomization. * Participant has a history of chronic liver disease (e.g., cirrhosis or fibrosis of the liver) * Participant has a known New York Heart Association Class III or Intravenous (IV) congestive heart failure. * Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (e.g., pulmonary embolism) within 12 weeks prior to randomization. * Uncontrolled hypertension or two or more blood pressure (BP) values of systolic BP (SBP) greater than or equal to 160 mmHg or diastolic BP (DBP) greater than or equal to 95 mmHg confirmed by repeat measurement within 2 weeks prior to randomization. * Participant has a diagnosis or suspicion (e.g., complex kidney cyst of Bosniak Category 2F or higher) of renal cell carcinoma on renal ultrasound within 12 weeks prior to randomization. * Participant has a history of malignancy, except the following: cancers determined to be cured or in remission for greater than or equal to 5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps. * Participant is positive for any of the following: Human Immunodeficiency Virus (HIV); hepatitis B surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab). * Participant has an active clinically significant infection manifested by White Blood Count (WBC) \> ULN, and/or fever, in conjunction with clinical signs or symptoms of infection within one week prior to randomization. * Participant has a known untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration and retinal vein occlusion. * Participant has had any prior organ transplant (that has not been explanted) or a scheduled organ transplantation. * Participant has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives or limit set by national law, whichever is longer, prior to the initiation of Screening. * Participant has an anticipated use of dapsone in any dose amount or chronic use of acetaminophen (paracetamol) \> 2.0 g/day during the treatment or follow-up period of the study. * Participant has a history of alcohol or drug abuse within 2 years prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Hemoglobin (Hb) Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy Prior to Hb Response | Baseline to week 24 | Hemoglobin (Hb) response was measured as Yes or No. Response Yes (responders) was defined as: Hb ≥11.0 g/dL and Hb increase from baseline by ≥ 1.0 g/dL, for participants with baseline Hb \> 8.0 g/dL; or Hb increase from baseline by ≥ 2.0 g/dL, for participants with baseline Hb ≤ 8.0 g/dL at two consecutive visits with available data separated at least 5 days during the first 24 weeks of treatment without having received rescue therapy (red blood cell (RBC) transfusion, erythropoiesis-stimulating agent (ESA), or intravenous (IV) iron prior to Hb response. This was the primary efficacy endpoint for EU (EMA). |
| Hb Change From Baseline (BL) to the Average Hb in Weeks 28-52 Regardless of Rescue Therapy | Baseline and weeks 28 to 52 | The change from baseline to the average Hb values across weeks 28 to 52 without having received rescue therapy. The Hb values from visit windows at weeks 28, 32, 36, 40, 44, 48 and 52 were used for the calculation of the average of weeks 28 to 52. This was the primary efficacy endpoint for US (FDA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron) | Baseline to week 104 (End of Treatment [EOT]) | The time to first use of rescue therapy was calculated (in years) as: (First event date - Analysis date of first dose intake + 1) / 365.25. The First event date was defined as Date of first dose of rescue medication during the efficacy emergent period and Analysis date of first dose intake was defined as date of first study drug dose intake collected on day 1. The Efficacy Emergent Period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or the end of treatment (EOT) visit, whichever occurred first. Data reported was analysed by Kaplan-Meier estimate for cumulative proportion. Medication onset date was the date of the first use of rescue medication. |
| Change From BL in Short Form (SF)-36 Vitality (VT) Sub-score to the Average VT Sub-score of Weeks 12 to 28 | Baseline and weeks 12 to 28 | Change from BL in SF-36 VT sub-score to the average value in weeks 12-28 was calculated using the physical component scores (PCS) of SF-36. The multi-purpose, short-form health survey has 36 questions with an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. The survey measures eight dimensions or scales: (1) physical functioning (PF) (10 items); (2) role limitations due to physical health problems (RP) (3 items); (3) bodily pain (BP) (2 items); (4) social functioning (SF) (2 items); (5) general health perceptions (GH) (5 items); (6) role limitations due to emotional problems (RE) (3 items); (7) vitality, energy or fatigue (VT) (4 items); and (8) mental health (MH) (5 items). The SF-36 scores ranged from 0-100 with higher scores indicating better health status. |
| Change From BL in SF-36 Physical Functioning (PF) Sub-score to the Average PF Sub-score of Weeks 12 to 28 | Baseline and weeks 12 to 28 | Change from baseline in SF-36 PF normalized sub-score compared to the average PF sub-score of weeks 12 to 28. The multi-purpose, short-form health survey has 36 questions with an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Change from baseline in PF sub score of SF-36 to the average of weeks 12-28 was compared by treatment arm for all participants (primary analysis) and in the subsets of participants with baseline PF sub score below 35 and equal or above 35. The SF-36 scores ranged from 0-100 with higher scores indicating better health status. All available SF-36 PF values were used i.e., both scheduled and unscheduled for the calculation of the average PF sub-score of weeks 12 to 28. |
| Change From BL in Mean Arterial Pressure (MAP) to the Average MAP of Weeks 20 to 28 | Baseline and weeks 20 to 28 | The MAP was derived for each visit from the average systolic (SBP) and diastolic blood pressure (DBP) calculated for each visit using the three readings and the following equation: MAP = (2/3) \* DBP + (1/3) \* SBP. Baseline assessment was the assessment on day 1 (average of the three readings). If the baseline assessment was missing, then the latest available value prior to first drug administration was used. |
| Time to First Occurrence of Hypertension | Baseline and year 0.5, year 1, year 1.5 and year 2 | Occurrence of hypertension was defined as SBP increase from BL ≥20 mmHg and SBP \>170 mmHg or DBP increase from BL ≥15 mmHg and DBP ≥110 mmHg. Time to first occurrence of hypertension was defined as first date where SBP criterion or DBP criterion is met, whichever occurred first. Data was analysed using Kaplan-Meier estimate for cumulative proportion. |
| Rate of Progression of CKD Measured by Annualized Estimated Glomerular Filtration Rate (eGFR) Slope Over Time | Baseline to week 108 | Annualized eGFR slope over time was estimated by a random slopes and intercepts model using all available eGFR values (one baseline and all post-treatment values up to EOT period or start of dialysis adjusted on baseline Hb, region, CV history at baseline and the interaction terms (baseline eGFR by timepoint and baseline Hb by timepoint). All assessments collected after initiation of chronic dialysis (acute or chronic) are excluded from the analysis. Baseline assessment was the assessment from day 1 visit. If this value was missing, the value from screening visit was used. |
| Average Level of Hb Over Weeks 28 to 36 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period | Weeks 28 to 36 | All scheduled and unscheduled hemoglobin values from weeks 28 to 36 were taken into account for calculating the average values. |
| Average Level of Hb Over Weeks 44 to 52 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period | Weeks 44 to 52 | All scheduled and unscheduled hemoglobin values from weeks 44 to 52 were taken into account for calculating the average values. |
| Average Level of Hb Over Weeks 96 to 104 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period | Weeks 96 to 104 | All scheduled and unscheduled hemoglobin values from weeks 96 to 104 were taken into account for calculating the average values. |
| Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint | Baseline to week 24 | Hb response was measured as Yes or No; Yes was defined as Hb ≥11.0 g/dL and Hb increase from baseline by ≥ 1.0 g/dL, for participants with baseline Hb \> 8.0 g/dL; or Hb increase from baseline by ≥ 2.0 g/dL, for participants with baseline Hb ≤ 8.0 g/dL. For a participant without rescue therapy before Hb response (defined in 1 primary outcome), the time to achieve Hb response was calculated (in weeks) as: (First event date - Analysis date of first dose intake + 1) / 7 where First event date was defined as First date of both values that met the criteria for response. Participants who discontinued or received rescue therapy prior to the first Hb response or before the second consecutive Hb value defined as a response were classified as non responders and were censored at week 24 or end of efficacy emergent period, whichever came first. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. |
| Hb Change From BL to Each Post-Dosing Time Point | Baseline (day 1) and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104 | All scheduled and unscheduled hemoglobin values that belong to each visit window were taken into account using one value per analysis window. 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 Change From BL to the Average Hb Value of Weeks 28-36 Regardless of the Use of Rescue Therapy | Baseline and weeks 28 to 36 | The Hb values from visit windows from weeks 28 to 36 were used for the calculation of the average regardless 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-dosing). |
| Hb Change From BL to the Average Hb Value of Weeks 44-52 Regardless of the Use of Rescue Therapy | Baseline and weeks 44 to 52 | The Hb values from visit windows from weeks 44 to 52 were used for the calculation of the average regardless 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-dosing). |
| Hb Change From BL to the Average Hb Value of Weeks 96-104 Regardless of the Use of Rescue Therapy | Baseline and weeks 96 to 104 | The Hb values from visit windows from weeks 96 to 104 were used for the calculation of the average regardless 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-dosing). |
| Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 28-36 Without Use of Rescue Therapy | Baseline and weeks 28 to 36 | The percentage of Hb values measured during weeks 28-36 within 10.0 -12.0 g/dL, without having received rescue therapy within 6 weeks prior to and during the 8-week evaluation period is reported. |
| Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 44-52 Without Use of Rescue Therapy | Baseline and weeks 44 to 52 | The percentage of Hb values measured during weeks 44-52 with values within 10.0 - 12.0 g/dL, without having received rescue therapy within 6 weeks prior to and during the 8-week evaluation period is reported. |
| Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 96-104 Without Use of Rescue Therapy | Baseline and weeks 96 to 104 | The percentage of Hb values measured during weeks 96-104 within 10.0 -12.0 g/dL, without having received rescue therapy within 6 weeks prior to and during the 8-week evaluation period is reported. |
| Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104 | Change from baseline to each planned assessment for ratio of ApoB/ApoA1 is reported. Baseline was defined as the value on day 1. If this value was missing, the latest value prior to first study drug administration was used. |
| Time to First Hospitalization | Baseline to week 104 | Time to first hospitalization was defined in years as the First event date during the Efficacy Emergent Period - (Analysis date of first dose intake +1)/365.25. The first event date was defined as the Date of first admission. The Efficacy Emergent Period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or EOT visit, whichever occured first. Analysis date of first dose intake was defined as the date of first study drug intake collected on day 1 visit. For participants who experienced more than one hospitalization, only their first event following study treatment was used. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. |
| Number of Days of Hospitalization Per Patient Exposure Year (PEY) | Baseline to week 104 | The sum of the durations of all hospitalizations in days was adjusted for the duration of exposure. Derived only for participants with at least one hospitalization. The number of days of hospitalization per PEY was calculated as the sum of the durations of all hospitalizations in days \[Minimum (Date of discharge, End of Efficacy Emergent Period) - Date of admission + 1\] / \[Duration of Efficacy Emergent Period in days / 365.25\]. Participants can have more than one hospitalization. |
| Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment | Baseline to week 24 | Time to first use of rescue therapy in years. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. |
| Time to First Use of RBC Transfusions | Baseline to week 104 | Time to First Use of RBC Transfusions during efficacy emergent period. For participants who have experienced more than one RBC transfusion, only their first event following study treatment was used. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or EOT visit, whichever occured first. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. |
| Mean Monthly Number of RBC Packs | Baseline to week 104 | During efficacy emergent period, the mean monthly number of RBC packs was calculated as the sum of 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 7 days after the analysis date of last dose or EOT visit, whichever occured first. In case of missing number of packs, values were estimated based on 1 unit for packed cells = 250 mL or 1 unit for whole blood = 500 mL. Participants without RBC transfusion were included with a value of zero. No estimation if values were missing. |
| Mean Monthly Volume of Blood Transfused | Baseline to week 104 | During efficacy emergent period, the mean monthly volume of blood transfused was calculated as the sum of blood volume 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 7 days after the analysis date of last dose or EOT visit, whichever occurred first. The mean monthly volume transfused was calculated as the sum of the volume transfused between the first dose and up to the last dose in the period divided by duration (in days) and multiplied by 28 days. Participants without RBC transfusion were included with a value of zero. |
| Time to First Use of ESA Rescue Therapy | Baseline to week 104 | Time to First Use of ESA Rescue Therapy during efficacy emergent period. For participants with use of ESA, the time to first use of ESA was calculated as (First event date - Analysis date of first dose intake + 1) / 365.25. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or EOT visit, whichever occured first. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. Participants without ESA rescue were censored at the end of treatment. |
| Time to First Use of IV Iron | Baseline to week 104 | Time to first use of IV iron during efficacy emergent period in years. For participants with use of IV iron, the time to first use of IV iron was calculated as (First event date - Analysis date of first dose intake + 1) / 365.25. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or EOT visit, whichever occurred first.Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. |
| Change From BL to Each Post-Dosing Visit in Total Cholesterol | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104 | Change from baseline to each planned assessment for total cholesterol is reported. Baseline was defined as the value on day 1. If the value was missing, the latest value prior to first study drug administration was used. |
| Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104 | Change from baseline to each planned assessment for LDL/HDL ratio is reported. Baseline was defined as the value on Day 1. If this value was missing, the latest value prior to first study drug administration was used. |
| Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104 | Change from baseline to each planned assessment for non-HDL is reported. Baseline was defined as the value on day 1. If this value was missing, the latest value prior to first study drug administration was used. |
| Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104 | Change from baseline to each planned assessment for apolipoproteins A1 is reported. Baseline was defined as the value on day 1. If this value was missing, the latest value prior to first study drug administration was used. |
| Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104 | Change from baseline to each planned assessment for apolipoproteins B is reported. Baseline was defined as the value on day 1. If this value was missing, the latest value prior to first study drug administration was used. |
| Percentage of Participants With Mean LDL Cholesterol <100 mg/dL Calculated Over Weeks 12 to 28 | Weeks 12 to 28 | Mean LDL cholesterol \<100 mg/dL over weeks 12 to 28 was defined as a binary variable (Yes/No), where Yes was defined as mean LDL cholesterol \<100 mg/dL over weeks 12 to 28. Participants without any LDL value within this duration were excluded. |
| Percentage of Participants Who Have Achieved Antihypertensive Treatment Goal in CKD Participants Over Weeks 12-28 | Weeks 12 to 28 | Occurrence of achieved antihypertensive treatment goal was defined as the average SBP \< 130 mmHg and the average DBP \< 80 mmHg over the period of weeks 12-28. Participants without any blood pressure measurement were excluded. |
| Change From BL to the Average Value of Weeks 12-28 in Quality of Life (QoL) SF-36 Physical Component Score (PCS) | Baseline and weeks 12 to 28 | The 36-Item short-form health survey (SF-36) is a multi-purpose survey with 36 questions. It provides an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. For each scale scores range from 0-100. The physical component score was calculated based on the results of the SF-36 scores. Higher scores indicate better health status. |
| Change From BL to the Average Value of Weeks 12-28 in Anemia Subscale (Ans) of Functional Assessment of Cancer Therapy (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 12-28 in Total FACT-An Score | Baseline and weeks 12 to 28 | Baseline FACT-An Total Score was defined as the FACT-An Total score 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 Value of Weeks 12-28 in the Euroqol Questionnaire - 5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score | Baseline and weeks 12 to 28 | The Euroqol Questionnaire - 5 Dimensions 5 Levels (EQ-5D 5L) is a self-reported questionnaire. The EQ-5D 5L is used as a measure of respondents' Health Related Quality of Life (HRQoL). The EQ-5D 5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The EQ-5D 5L descriptive system comprises of 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 answers are labeled 'Best imaginable health state' and 'Worst imaginable health state' with higher scores for higher HRQoL. |
| Change From BL to the Average Value of Weeks 12-28 in Overall Work Impairment Due to Anaemic Symptoms | Baseline and weeks 12 to 28 | Work productivity and activity impairment: anemic symptoms (WPAI:ANS) questionnaire version 2 was used to measure work and activity impairment during the last seven days due to anemia. It is self-assessed questionnaire which consists of 6 questions covering work and daily activities. Questions include asking if participant is working, how many hours the person missed work due to anemic symptoms, how many hours the person missed work due to other reasons, how many hours participant actually worked and how the anemic symptoms impacted their productivity and ability to do daily activities. For the last 2 questions, they were scored from 0-10 with 0 identifying no effect on work and 10 completely prevented from working. Overall work impairment due to ANS was calculated as 100 x Q2/(Q2+Q4)+\[(1-Q2/(Q2+Q4))x(Q5/10)\]. Scores were calculated with the formula to derive the overall work impairment on each timepoints in percentage, and then changes of the percentage from baseline are reported. |
| Percentage of Participants in Each Category in Patients' Global Impression of Change (PGIC) | Week 12 to 28 | The Patients' Global Impression of Change (PGIC) is a participant-rated instrument that measures change in participants overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). |
| Change From BL to Each Study Visit in Serum Hepcidin | Baseline and weeks 4,12,20,36,52,104 | Baseline was assessed on 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 to Each Study Visit in Serum Ferritin | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 | Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
| Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 | Baseline was assessed on 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 to Each Study Visit in Serum HbA1c Level | Baseline and weeks 12, 28, 36, 44, 60, 84, 104 | HbA1c was measured at each timepoint and presented in 'fraction of 1' unit by dividing the values in percentage by 100, in order to fit for CDISC (Clinical Data Interchange Standards Consortium) standard terminology. Changes from baseline to each timepoint were reported in unit 'fraction of 1'. Baseline was assessed on 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 to Each Study Visit in Fasting Blood Glucose | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 | Baseline was assessed on 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. |
| Hb Change From BL to the Average Hb in Weeks 28-36 Without Having Received Rescue Therapy Within 6 Weeks Prior to and During 8-Week Evaluation Period | Baseline and weeks 28 to 36 | The Hb values from visit windows at weeks 28, 32 and 36 were used for the calculation of the average of weeks 28 to 36. |
| Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 | Baseline assessment was the 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. To compute the geometric mean of serum Cr (ratio) and associated 95% CI, the mean of log-transformed serum Cr (ratio) values and associated 95% CI are back-transformed to the raw scale. All assessments collected after initiation of dialysis (acute or chronic) were excluded from the analysis. |
| Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Baseline and year 0.5, year 1, year 1.5 and year 2 | The endpoint was defined as time to doubling serum creatinine or chronic dialysis or renal transplant what ever came first. Time to event was defined as (First event date - Analysis date of first dose intake + 1) / 365.25. First event date was defined as date of dialysis or date of renal transplant (whichever occurred first) and analysis date of first dose intake was defined as date of first study drug dose intake collected on day 1 visit. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. The data evaluated until the safety emergent period, which was defined as the evaluation period from analysis date of first drug intake up to 28 days after the analysis last dose, and results were presented for every 6 months up to 2 years. |
| Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Baseline and year 0.5, year 1, year 1.5 and year 2 | CKD progression was defined as date of occurrence of chronic dialysis or date of renal transplant or doubled serum creatinine or date of death, whichever came first. The time to CKD progression was calculated (in years) as (First event date - Analysis date of first dose intake + 1) / 365.25. First event date was defined as first occurrence of serum creatinine being doubled compared with baseline, first occurrence of chronic dialysis or renal transplant, occurrence of participants who died (whichever occurred first). Analysis date of first dose intake was defined as date of first study drug dose intake collected on day 1 visit. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. The data evaluated until the safety emergent period, which was defined as the evaluation period from analysis date of first drug intake up to 28 days after the analysis last dose, and results were presented for every 6 months up to 2 years. |
| Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Baseline and year 0.5, year 1, year 1.5 and year 2 | All eGFR values collected during the safety emergent period are considered, excluding those collected on or after initiation of dialysis (acute or chronic). The First event date was defined as First occurrence of 40% decrease in eGFR from baseline, first occurrence of chronic dialysis or renal transplant (whichever occurred first and Analysis date of first dose intake was defined as date of first study drug dose intake collected on day 1 visit. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the analysis date of last dose or end of study (EOS), whichever occurred first. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. The data evaluated until the safety emergent period, which was defined as the evaluation period from analysis date of first drug intake up to 28 days after the analysis last dose, and results were presented for every 6 months up to 2 years. |
| Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Baseline and weeks 12, 24, 36, 52, 64, 76, 88, 104 | Baseline assessment was the assessment from day 1 visit. If baseline value was missing, value from screening visit was used. In case of missing data, no imputation rules were applied. To compute the geometric mean of albumin/creatinine ratio in urine and associated 95% CI, the mean of log-transformed albumin/creatinine ratio in urine values (ratio) and associated 95% CI are back-transformed to the raw scale. All assessments collected after initiation of dialysis (acute or chronic) were excluded from the analysis. |
| Change From BL in Low-Density Lipoprotein (LDL) Cholesterol (Regardless of Fasting Status) to the Average LDL Cholesterol of Weeks 12 to 28 | Baseline and weeks 12 to 28 | Analysis was completed on all values collected on day 1 and weeks 12, 20 and 28. |
Countries
Belarus, Belgium, Bulgaria, Colombia, Dominican Republic, Estonia, Georgia, Greece, Guatemala, Hungary, Italy, Panama, Peru, Poland, Romania, Russia, Serbia, South Africa, Spain, Turkey (Türkiye), Ukraine, United Kingdom
Participant flow
Recruitment details
Study population consisted of anemic participants with stages 3, 4 or 5 chronic kidney disease (CKD) (Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m\^2) who were not on dialysis. Participants were recruited from 125 study centers located in 22 countries.
Pre-assignment details
A total of 594 participants with CKD were randomized to one of the 2 treatment arms in a 2:1 ratio receiving roxadustat or placebo. Anemia was defined as a mean Hb ≤ 10.0 g/dL upon repeated measurements during the screening period. Participants needed a ferritin ≥30 ng/mL (≥ 67.4 pmol/L) and transferrin saturation (TSAT) ≥ 5%.
Participants by arm
| Arm | Count |
|---|---|
| Roxadustat Participants received roxadustat according to the tiered weight-based approach, with starting doses of 70 mg given thrice weekly (TIW) to participants weighing up to 70 kg and 100 mg given TIW to participants weighing more than 70 kg. Dose-titration was performed based upon regular measurement of Hb levels until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL. Participants received roxadustat for at least 52 weeks up to a maximum of 104 weeks. | 391 |
| Placebo Participants received matching placebo according to the tiered weight-based approach, with starting doses of 70 mg given thrice weekly (TIW) to participants weighing up to 70 kg and 100 mg given TIW to participants weighing more than 70 kg. Dose-titration was performed based upon regular measurement of Hb levels until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL. Participants received matching placebo for at least 52 weeks up to a maximum of 104 weeks. | 203 |
| Total | 594 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 21 | 9 |
| Overall Study | Death | 39 | 16 |
| Overall Study | Lack of Efficacy | 3 | 26 |
| Overall Study | Lost to Follow-up | 5 | 1 |
| Overall Study | Miscellaneous | 6 | 2 |
| Overall Study | Non-compliance with study drug | 3 | 0 |
| Overall Study | Physician Decision | 7 | 8 |
| Overall Study | Progressive Disease | 1 | 0 |
| Overall Study | Protocol Deviation | 3 | 0 |
| Overall Study | Withdrawal by Subject | 58 | 52 |
Baseline characteristics
| Characteristic | Roxadustat | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 60.6 Year STANDARD_DEVIATION 13.5 | 61.0 Year STANDARD_DEVIATION 13.6 | 61.7 Year STANDARD_DEVIATION 13.8 |
| Baseline Estimated Glomerular Filtration Rate (eGFR) | 16.5 mL/min/1.73m^2 STANDARD_DEVIATION 10.2 | 16.7 mL/min/1.73m^2 STANDARD_DEVIATION 10.7 | 17.2 mL/min/1.73m^2 STANDARD_DEVIATION 11.7 |
| Baseline Hemoglobin (Hb) Value | 9.08 g/dL STANDARD_DEVIATION 0.76 | 9.08 g/dL STANDARD_DEVIATION 0.75 | 9.10 g/dL STANDARD_DEVIATION 0.72 |
| History of Diabetes (Type 1 or 2) No | 245 Participants | 359 Participants | 114 Participants |
| History of Diabetes (Type 1 or 2) Yes | 146 Participants | 235 Participants | 89 Participants |
| Iron Repletion at Baseline TSAT >= 20% and Ferritin >= 100 ng/mL | 204 Participants | 313 Participants | 109 Participants |
| Iron Repletion at Baseline TSAT < 20% or Ferritin < 100 ng/mL | 187 Participants | 281 Participants | 94 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 9 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 13 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 37 Participants | 55 Participants | 18 Participants |
| Race (NIH/OMB) White | 335 Participants | 517 Participants | 182 Participants |
| Sex: Female, Male Female | 222 Participants | 326 Participants | 104 Participants |
| Sex: Female, Male Male | 169 Participants | 268 Participants | 99 Participants |
| Time From Chronic Kidney Disease (CKD) Diagnosis | 5.65 Years STANDARD_DEVIATION 7.02 | 5.40 Years STANDARD_DEVIATION 6.69 | 4.91 Years STANDARD_DEVIATION 5.99 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 45 / 391 | 20 / 203 |
| other Total, other adverse events | 204 / 391 | 103 / 203 |
| serious Total, serious adverse events | 241 / 391 | 115 / 203 |
Outcome results
Primary
Hb Change From Baseline (BL) to the Average Hb in Weeks 28-52 Regardless of Rescue Therapy
The change from baseline to the average Hb values across weeks 28 to 52 without having received rescue therapy. The Hb values from visit windows at weeks 28, 32, 36, 40, 44, 48 and 52 were used for the calculation of the average of weeks 28 to 52. This was the primary efficacy endpoint for US (FDA).
Time frame: Baseline and weeks 28 to 52
Population: The analysis population was All Randomized, and it consisted of all randomized participants with available data at all time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Hb Change From Baseline (BL) to the Average Hb in Weeks 28-52 Regardless of Rescue Therapy | 1.992 g/dL |
| Placebo | Hb Change From Baseline (BL) to the Average Hb in Weeks 28-52 Regardless of Rescue Therapy | 0.300 g/dL |
Comparison: The Analysis of Covariance (ANCOVA) with Multiple Imputations (MI) model, adjusting for covariates was used for the analysis. The model included treatment as fixed factor, region and history of CV disease as class factors and baseline Hb, baseline eGFR as continuous covariates. Superiority of roxadustat versus placebo was considered successful if the lower bound of the two-sided 95% confidence interval of the difference between treatment arms (roxadustat minus placebo) was higher than 0.p-value: <0.00195% CI: [1.52, 1.86]ANCOVA
Primary
Percentage of Participants With a Hemoglobin (Hb) Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy Prior to Hb Response
Hemoglobin (Hb) response was measured as Yes or No. Response Yes (responders) was defined as: Hb ≥11.0 g/dL and Hb increase from baseline by ≥ 1.0 g/dL, for participants with baseline Hb \> 8.0 g/dL; or Hb increase from baseline by ≥ 2.0 g/dL, for participants with baseline Hb ≤ 8.0 g/dL at two consecutive visits with available data separated at least 5 days during the first 24 weeks of treatment without having received rescue therapy (red blood cell (RBC) transfusion, erythropoiesis-stimulating agent (ESA), or intravenous (IV) iron prior to Hb response. This was the primary efficacy endpoint for EU (EMA).
Time frame: Baseline to week 24
Population: The analysis population was the full analysis set (FAS), which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Percentage of Participants With a Hemoglobin (Hb) Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy Prior to Hb Response | 79.2 Percentage of Participants |
| Placebo | Percentage of Participants With a Hemoglobin (Hb) Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy Prior to Hb Response | 9.9 Percentage of Participants |
Comparison: The Cochran-Mantel-Haenszel (CMH) test was adjusted by region, history of of cardiovascular, cerebrovascular or thromboembolic (CV) disease, baseline Hb and baseline estimated glomerular filtration rate (eGFR). Superiority of roxadustat versus placebo was to be declared if the lower bound of the two-sided 95% confidence interval of the CMH odds ratio was higher than 1.p-value: <0.00195% CI: [20.48, 58.93]Cochran-Mantel-Haenszel
Secondary
Average Level of Hb Over Weeks 28 to 36 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period
All scheduled and unscheduled hemoglobin values from weeks 28 to 36 were taken into account for calculating the average values.
Time frame: Weeks 28 to 36
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Average Level of Hb Over Weeks 28 to 36 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period | 11.106 g/dL |
| Placebo | Average Level of Hb Over Weeks 28 to 36 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period | 9.468 g/dL |
Comparison: Average Level of Hb Over Weeks 28 to 36. A Mixed Model of Repeated Measures was applied using the visits over weeks 28 to 36. The results were based on the estimated difference between the two treatment arms by visit based on this MMRM model. The model included treatment arm, region, CV History, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.44, 1.84]Mixed Models Analysis
Secondary
Average Level of Hb Over Weeks 44 to 52 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period
All scheduled and unscheduled hemoglobin values from weeks 44 to 52 were taken into account for calculating the average values.
Time frame: Weeks 44 to 52
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Average Level of Hb Over Weeks 44 to 52 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period | 10.984 g/dL |
| Placebo | Average Level of Hb Over Weeks 44 to 52 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period | 9.381 g/dL |
Comparison: Average Level of Hb Over Weeks 44 to 52. A Mixed Model of Repeated Measures was applied using the visits over weeks 44 to 52. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.39, 1.82]Mixed Models Analysis
Secondary
Average Level of Hb Over Weeks 96 to 104 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period
All scheduled and unscheduled hemoglobin values from weeks 96 to 104 were taken into account for calculating the average values.
Time frame: Weeks 96 to 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Average Level of Hb Over Weeks 96 to 104 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period | 10.816 g/dL |
| Placebo | Average Level of Hb Over Weeks 96 to 104 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period | 9.324 g/dL |
Comparison: Average Level of Hb Over Weeks 96 to 104. A Mixed Model of Repeated Measures was applied using the visits over weeks 96 to 104. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.14, 1.85]Mixed Models Analysis
Secondary
Change From BL in Low-Density Lipoprotein (LDL) Cholesterol (Regardless of Fasting Status) to the Average LDL Cholesterol of Weeks 12 to 28
Analysis was completed on all values collected on day 1 and weeks 12, 20 and 28.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL in Low-Density Lipoprotein (LDL) Cholesterol (Regardless of Fasting Status) to the Average LDL Cholesterol of Weeks 12 to 28 | -0.650 mmol/L |
| Placebo | Change From BL in Low-Density Lipoprotein (LDL) Cholesterol (Regardless of Fasting Status) to the Average LDL Cholesterol of Weeks 12 to 28 | 0.051 mmol/L |
Comparison: A Mixed Model of Repeated Measures has been applied up to week 28. The results were based on the estimated difference between the two treatment arms and overall mean effects during the period (weeks 12 to 28). The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb, baseline eGFR and baseline LDL as continuous variables.p-value: <0.00195% CI: [-0.83, -0.57]Mixed Models Analysis
Secondary
Change From BL in Mean Arterial Pressure (MAP) to the Average MAP of Weeks 20 to 28
The MAP was derived for each visit from the average systolic (SBP) and diastolic blood pressure (DBP) calculated for each visit using the three readings and the following equation: MAP = (2/3) \* DBP + (1/3) \* SBP. Baseline assessment was the assessment on day 1 (average of the three readings). If the baseline assessment was missing, then the latest available value prior to first drug administration was used.
Time frame: Baseline and weeks 20 to 28
Population: The analysis population was the per protocol set (PPS), which consisted of all FAS participants who did not meet any reasons for exclusion from the PPS and had all available data at all time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL in Mean Arterial Pressure (MAP) to the Average MAP of Weeks 20 to 28 | -0.814 mmHg |
| Placebo | Change From BL in Mean Arterial Pressure (MAP) to the Average MAP of Weeks 20 to 28 | -1.656 mmHg |
Comparison: Mixed Model of Repeated Measures was applied using the visits up to week 28. The results were based on the estimated difference between the two treatment arms with overall mean effects throughout the evaluation period (weeks 20 to 28). The model included treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline MAP, baseline Hb, baseline eGFR as continuous covariates.p-value: =0.18295% CI: [-0.4, 2.08]Mixed Models Analysis
Secondary
Change From BL in SF-36 Physical Functioning (PF) Sub-score to the Average PF Sub-score of Weeks 12 to 28
Change from baseline in SF-36 PF normalized sub-score compared to the average PF sub-score of weeks 12 to 28. The multi-purpose, short-form health survey has 36 questions with an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Change from baseline in PF sub score of SF-36 to the average of weeks 12-28 was compared by treatment arm for all participants (primary analysis) and in the subsets of participants with baseline PF sub score below 35 and equal or above 35. The SF-36 scores ranged from 0-100 with higher scores indicating better health status. All available SF-36 PF values were used i.e., both scheduled and unscheduled for the calculation of the average PF sub-score of weeks 12 to 28.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL in SF-36 Physical Functioning (PF) Sub-score to the Average PF Sub-score of Weeks 12 to 28 | 1.344 Units on a Scale |
| Placebo | Change From BL in SF-36 Physical Functioning (PF) Sub-score to the Average PF Sub-score of Weeks 12 to 28 | 0.632 Units on a Scale |
Comparison: A Mixed Model of Repeated Measures has been applied using the visits up to week 28. The results were based on the estimated difference between the two treatment arms and overall mean effects throughout the evaluation period (weeks 12 to 28). The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline SF-36 PF, baseline Hb and baseline eGFR as continuous variables.p-value: =0.2795% CI: [-0.56, 1.98]Mixed Models Analysis
Secondary
Change From BL in Short Form (SF)-36 Vitality (VT) Sub-score to the Average VT Sub-score of Weeks 12 to 28
Change from BL in SF-36 VT sub-score to the average value in weeks 12-28 was calculated using the physical component scores (PCS) of SF-36. The multi-purpose, short-form health survey has 36 questions with an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. The survey measures eight dimensions or scales: (1) physical functioning (PF) (10 items); (2) role limitations due to physical health problems (RP) (3 items); (3) bodily pain (BP) (2 items); (4) social functioning (SF) (2 items); (5) general health perceptions (GH) (5 items); (6) role limitations due to emotional problems (RE) (3 items); (7) vitality, energy or fatigue (VT) (4 items); and (8) mental health (MH) (5 items). The SF-36 scores ranged from 0-100 with higher scores indicating better health status.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL in Short Form (SF)-36 Vitality (VT) Sub-score to the Average VT Sub-score of Weeks 12 to 28 | 2.788 Units on a Scale |
| Placebo | Change From BL in Short Form (SF)-36 Vitality (VT) Sub-score to the Average VT Sub-score of Weeks 12 to 28 | 1.661 Units on a Scale |
Comparison: A Mixed Model of Repeated Measures has been applied using the visits up to week 28. The results were based on the estimated difference between the two treatment arms and overall mean effects throughout the evaluation period (weeks 12 to 28). The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline SF-36 VT, baseline Hb and baseline eGFR as continuous variables.p-value: =0.09395% CI: [-0.19, 2.44]Mixed Models Analysis
Secondary
Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1)
Change from baseline to each planned assessment for apolipoproteins A1 is reported. Baseline was defined as the 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 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 20 | -0.114 g/L | Standard Deviation 0.245 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 44 | -0.135 g/L | Standard Deviation 0.259 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 12 | -0.131 g/L | Standard Deviation 0.254 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 52 | -0.090 g/L | Standard Deviation 0.26 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 28 | -0.104 g/L | Standard Deviation 0.265 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 68 | -0.157 g/L | Standard Deviation 0.31 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 8 | -0.148 g/L | Standard Deviation 0.229 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 84 | -0.132 g/L | Standard Deviation 0.282 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 36 | -0.101 g/L | Standard Deviation 0.252 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 104 | -0.098 g/L | Standard Deviation 0.227 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 4 | -0.168 g/L | Standard Deviation 0.232 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 104 | 0.070 g/L | Standard Deviation 0.136 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 4 | 0.013 g/L | Standard Deviation 0.19 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 8 | 0.008 g/L | Standard Deviation 0.227 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 12 | 0.004 g/L | Standard Deviation 0.203 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 20 | 0.036 g/L | Standard Deviation 0.222 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 28 | 0.006 g/L | Standard Deviation 0.233 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 36 | 0.002 g/L | Standard Deviation 0.223 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 44 | -0.013 g/L | Standard Deviation 0.268 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 52 | -0.028 g/L | Standard Deviation 0.248 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 68 | 0.018 g/L | Standard Deviation 0.204 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) | Week 84 | 0.060 g/L | Standard Deviation 0.196 |
Secondary
Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB)
Change from baseline to each planned assessment for apolipoproteins B is reported. Baseline was defined as the 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 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 20 | -12.709 mg/dL | Standard Deviation 24.424 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 44 | -15.593 mg/dL | Standard Deviation 26.594 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 12 | -14.935 mg/dL | Standard Deviation 24.613 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 52 | -14.122 mg/dL | Standard Deviation 27.503 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 28 | -13.782 mg/dL | Standard Deviation 28.634 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 68 | -18.746 mg/dL | Standard Deviation 28.633 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 8 | -19.483 mg/dL | Standard Deviation 21.009 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 84 | -20.133 mg/dL | Standard Deviation 28.134 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 36 | -14.866 mg/dL | Standard Deviation 25.469 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 104 | -10.917 mg/dL | Standard Deviation 22.885 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 4 | -19.891 mg/dL | Standard Deviation 20.669 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 104 | 14.750 mg/dL | Standard Deviation 20.271 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 4 | 2.059 mg/dL | Standard Deviation 22.22 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 8 | 2.059 mg/dL | Standard Deviation 20.297 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 12 | 0.278 mg/dL | Standard Deviation 21.707 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 20 | 5.711 mg/dL | Standard Deviation 25.883 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 28 | 9.746 mg/dL | Standard Deviation 26.864 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 36 | 6.623 mg/dL | Standard Deviation 25.895 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 44 | 3.222 mg/dL | Standard Deviation 30.771 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 52 | 4.676 mg/dL | Standard Deviation 31.44 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 68 | 2.786 mg/dL | Standard Deviation 28.9 |
| Placebo | Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) | Week 84 | 12.500 mg/dL | Standard Deviation 32.152 |
Secondary
Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio
Change from baseline to each planned assessment for LDL/HDL ratio is reported. Baseline was defined as the 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 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 20 | -0.250 Ratio | Standard Deviation 1.024 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 44 | -0.368 Ratio | Standard Deviation 1.099 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 12 | -0.268 Ratio | Standard Deviation 0.905 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 52 | -0.429 Ratio | Standard Deviation 1.125 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 28 | -0.313 Ratio | Standard Deviation 1.057 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 68 | -0.466 Ratio | Standard Deviation 1.219 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 8 | -0.374 Ratio | Standard Deviation 0.952 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 84 | -0.509 Ratio | Standard Deviation 1.307 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 36 | -0.349 Ratio | Standard Deviation 1.04 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 104 | -0.414 Ratio | Standard Deviation 1.306 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 4 | -0.331 Ratio | Standard Deviation 0.777 |
| Placebo | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 104 | 0.105 Ratio | Standard Deviation 0.873 |
| Placebo | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 4 | 0.076 Ratio | Standard Deviation 0.635 |
| Placebo | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 8 | 0.068 Ratio | Standard Deviation 0.685 |
| Placebo | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 12 | 0.081 Ratio | Standard Deviation 0.915 |
| Placebo | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 20 | 0.155 Ratio | Standard Deviation 0.788 |
| Placebo | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 28 | 0.156 Ratio | Standard Deviation 0.861 |
| Placebo | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 36 | 0.157 Ratio | Standard Deviation 1.053 |
| Placebo | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 44 | 0.099 Ratio | Standard Deviation 1.198 |
| Placebo | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 52 | 0.019 Ratio | Standard Deviation 1.076 |
| Placebo | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 68 | 0.052 Ratio | Standard Deviation 0.955 |
| Placebo | Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio | Week 84 | 0.114 Ratio | Standard Deviation 1.113 |
Secondary
Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol
Change from baseline to each planned assessment for non-HDL is reported. Baseline was defined as the 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 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 20 | -0.638 mmol/L | Standard Deviation 1.175 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 44 | -0.751 mmol/L | Standard Deviation 1.19 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 12 | -0.709 mmol/L | Standard Deviation 1.107 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 52 | -0.751 mmol/L | Standard Deviation 1.276 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 28 | -0.710 mmol/L | Standard Deviation 1.227 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 68 | -0.882 mmol/L | Standard Deviation 1.325 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 8 | -0.909 mmol/L | Standard Deviation 1.064 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 84 | -0.939 mmol/L | Standard Deviation 1.518 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 36 | -0.711 mmol/L | Standard Deviation 1.239 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 104 | -0.839 mmol/L | Standard Deviation 1.554 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 4 | -0.969 mmol/L | Standard Deviation 0.989 |
| Placebo | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 104 | 0.174 mmol/L | Standard Deviation 1.014 |
| Placebo | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 4 | 0.118 mmol/L | Standard Deviation 0.789 |
| Placebo | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 8 | 0.070 mmol/L | Standard Deviation 0.864 |
| Placebo | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 12 | 0.078 mmol/L | Standard Deviation 1.05 |
| Placebo | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 20 | 0.186 mmol/L | Standard Deviation 1.072 |
| Placebo | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 28 | 0.206 mmol/L | Standard Deviation 1.227 |
| Placebo | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 36 | 0.202 mmol/L | Standard Deviation 1.133 |
| Placebo | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 44 | 0.106 mmol/L | Standard Deviation 1.342 |
| Placebo | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 52 | 0.104 mmol/L | Standard Deviation 1.299 |
| Placebo | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 68 | 0.174 mmol/L | Standard Deviation 1.187 |
| Placebo | Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol | Week 84 | 0.089 mmol/L | Standard Deviation 1.343 |
Secondary
Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1
Change from baseline to each planned assessment for ratio of ApoB/ApoA1 is reported. Baseline was defined as the 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 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 20 | -0.043 Ratio | Standard Deviation 0.189 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 44 | -0.053 Ratio | Standard Deviation 0.22 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 12 | -0.059 Ratio | Standard Deviation 0.164 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 52 | -0.065 Ratio | Standard Deviation 0.207 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 28 | -0.066 Ratio | Standard Deviation 0.222 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 68 | -0.086 Ratio | Standard Deviation 0.212 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 8 | -0.084 Ratio | Standard Deviation 0.202 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 84 | -0.066 Ratio | Standard Deviation 0.21 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 36 | -0.070 Ratio | Standard Deviation 0.2 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 104 | -0.024 Ratio | Standard Deviation 0.126 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 4 | -0.073 Ratio | Standard Deviation 0.165 |
| Placebo | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 104 | 0.085 Ratio | Standard Deviation 0.132 |
| Placebo | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 4 | 0.010 Ratio | Standard Deviation 0.169 |
| Placebo | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 8 | 0.000 Ratio | Standard Deviation 0.184 |
| Placebo | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 12 | -0.006 Ratio | Standard Deviation 0.201 |
| Placebo | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 20 | 0.009 Ratio | Standard Deviation 0.198 |
| Placebo | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 28 | 0.063 Ratio | Standard Deviation 0.205 |
| Placebo | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 36 | 0.045 Ratio | Standard Deviation 0.213 |
| Placebo | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 44 | 0.031 Ratio | Standard Deviation 0.265 |
| Placebo | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 52 | 0.047 Ratio | Standard Deviation 0.266 |
| Placebo | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 68 | 0.001 Ratio | Standard Deviation 0.184 |
| Placebo | Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 | Week 84 | 0.058 Ratio | Standard Deviation 0.295 |
Secondary
Change From BL to Each Post-Dosing Visit in Total Cholesterol
Change from baseline to each planned assessment for total cholesterol is reported. Baseline was defined as the value on day 1. If the value was missing, the latest value prior to first study drug administration was used.
Time frame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 20 | -0.747 mmol/L | Standard Deviation 1.227 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 44 | -0.854 mmol/L | Standard Deviation 1.238 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 12 | -0.836 mmol/L | Standard Deviation 1.173 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 52 | -0.815 mmol/L | Standard Deviation 1.314 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 28 | -0.816 mmol/L | Standard Deviation 1.284 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 68 | -0.971 mmol/L | Standard Deviation 1.382 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 8 | -1.066 mmol/L | Standard Deviation 1.086 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 84 | -1.055 mmol/L | Standard Deviation 1.554 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 36 | -0.803 mmol/L | Standard Deviation 1.3 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 104 | -0.944 mmol/L | Standard Deviation 1.584 |
| Roxadustat | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 4 | -1.151 mmol/L | Standard Deviation 1.058 |
| Placebo | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 104 | 0.218 mmol/L | Standard Deviation 1.067 |
| Placebo | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 4 | 0.108 mmol/L | Standard Deviation 0.842 |
| Placebo | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 8 | 0.048 mmol/L | Standard Deviation 0.932 |
| Placebo | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 12 | 0.088 mmol/L | Standard Deviation 1.116 |
| Placebo | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 20 | 0.193 mmol/L | Standard Deviation 1.129 |
| Placebo | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 28 | 0.201 mmol/L | Standard Deviation 1.271 |
| Placebo | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 36 | 0.183 mmol/L | Standard Deviation 1.174 |
| Placebo | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 44 | 0.077 mmol/L | Standard Deviation 1.346 |
| Placebo | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 52 | 0.104 mmol/L | Standard Deviation 1.304 |
| Placebo | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 68 | 0.188 mmol/L | Standard Deviation 1.222 |
| Placebo | Change From BL to Each Post-Dosing Visit in Total Cholesterol | Week 84 | 0.102 mmol/L | Standard Deviation 1.284 |
Secondary
Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine
Baseline assessment was the assessment from day 1 visit. If baseline value was missing, value from screening visit was used. In case of missing data, no imputation rules were applied. To compute the geometric mean of albumin/creatinine ratio in urine and associated 95% CI, the mean of log-transformed albumin/creatinine ratio in urine values (ratio) and associated 95% CI are back-transformed to the raw scale. All assessments collected after initiation of dialysis (acute or chronic) were excluded from the analysis.
Time frame: Baseline and weeks 12, 24, 36, 52, 64, 76, 88, 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Roxadustat | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 12 | 1.08 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 24 | 1.19 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 36 | 1.21 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 52 | 1.28 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 64 | 1.25 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 76 | 1.12 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 88 | 1.10 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 104 | 1.92 Ratio |
| Placebo | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 104 | 0.38 Ratio |
| Placebo | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 12 | 1.06 Ratio |
| Placebo | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 64 | 0.96 Ratio |
| Placebo | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 24 | 1.16 Ratio |
| Placebo | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 88 | 0.51 Ratio |
| Placebo | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 36 | 1.04 Ratio |
| Placebo | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 76 | 0.82 Ratio |
| Placebo | Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine | Week 52 | 1.04 Ratio |
Secondary
Change From BL to Each Study Visit in Fasting Blood Glucose
Baseline was assessed on 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
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 104 | 0.125 mmol/L | Standard Deviation 2.633 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 4 | 0.107 mmol/L | Standard Deviation 2.573 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 8 | -0.103 mmol/L | Standard Deviation 3.179 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 12 | -0.100 mmol/L | Standard Deviation 3.504 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 20 | -0.302 mmol/L | Standard Deviation 4.052 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 28 | 0.160 mmol/L | Standard Deviation 3.489 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 36 | 0.015 mmol/L | Standard Deviation 2.991 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 44 | 0.073 mmol/L | Standard Deviation 2.683 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 52 | 0.048 mmol/L | Standard Deviation 4.348 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 60 | 0.130 mmol/L | Standard Deviation 2.907 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 68 | 0.185 mmol/L | Standard Deviation 2.831 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 76 | -0.015 mmol/L | Standard Deviation 2.031 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 84 | 0.495 mmol/L | Standard Deviation 3.117 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 92 | 0.612 mmol/L | Standard Deviation 2.494 |
| Roxadustat | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 100 | 0.405 mmol/L | Standard Deviation 2.932 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 104 | 0.237 mmol/L | Standard Deviation 3.938 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 52 | -0.086 mmol/L | Standard Deviation 4.883 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 4 | -0.076 mmol/L | Standard Deviation 2.73 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 84 | 0.435 mmol/L | Standard Deviation 2.037 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 8 | -0.162 mmol/L | Standard Deviation 3.118 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 60 | 1.190 mmol/L | Standard Deviation 3.946 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 12 | -0.153 mmol/L | Standard Deviation 4.629 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 100 | -0.699 mmol/L | Standard Deviation 2.161 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 20 | 0.523 mmol/L | Standard Deviation 2.981 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 68 | 0.698 mmol/L | Standard Deviation 3.386 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 28 | 0.045 mmol/L | Standard Deviation 3.281 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 92 | -0.861 mmol/L | Standard Deviation 3.298 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 36 | -0.117 mmol/L | Standard Deviation 2.812 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 76 | -0.671 mmol/L | Standard Deviation 5.148 |
| Placebo | Change From BL to Each Study Visit in Fasting Blood Glucose | Week 44 | 0.801 mmol/L | Standard Deviation 3.416 |
Secondary
Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio
Baseline assessment was the 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. To compute the geometric mean of serum Cr (ratio) and associated 95% CI, the mean of log-transformed serum Cr (ratio) values and associated 95% CI are back-transformed to the raw scale. All assessments collected after initiation of dialysis (acute or chronic) were excluded from the analysis.
Time frame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 28 | 1.12 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 60 | 1.09 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 8 | 1.03 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 68 | 1.11 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 36 | 1.12 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 76 | 1.13 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 20 | 1.08 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 84 | 1.13 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 44 | 1.12 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 92 | 1.19 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 12 | 1.04 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 100 | 1.16 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 52 | 1.12 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 104 | 1.16 Ratio |
| Roxadustat | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 4 | 1.01 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 104 | 1.28 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 4 | 1.05 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 8 | 1.07 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 12 | 1.07 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 20 | 1.09 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 28 | 1.13 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 36 | 1.12 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 44 | 1.16 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 52 | 1.15 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 60 | 1.15 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 68 | 1.24 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 76 | 1.23 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 84 | 1.19 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 92 | 1.22 Ratio |
| Placebo | Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio | Week 100 | 1.26 Ratio |
Secondary
Change From BL to Each Study Visit in Serum Ferritin
Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time frame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 28 | -184.501 pmol/L | Standard Deviation 341.114 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 60 | -133.499 pmol/L | Standard Deviation 467.931 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 8 | -247.955 pmol/L | Standard Deviation 295.92 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 68 | -159.906 pmol/L | Standard Deviation 453.802 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 36 | -142.876 pmol/L | Standard Deviation 608.677 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 76 | -149.226 pmol/L | Standard Deviation 408.126 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 20 | -198.349 pmol/L | Standard Deviation 284.015 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 84 | -103.284 pmol/L | Standard Deviation 530.021 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 44 | -137.151 pmol/L | Standard Deviation 352.715 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 92 | -106.070 pmol/L | Standard Deviation 464.192 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 12 | -265.812 pmol/L | Standard Deviation 318.433 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 100 | -119.647 pmol/L | Standard Deviation 452.209 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 52 | 164.009 pmol/L | Standard Deviation 564.396 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 104 | -107.814 pmol/L | Standard Deviation 458.702 |
| Roxadustat | Change From BL to Each Study Visit in Serum Ferritin | Week 4 | -221.827 pmol/L | Standard Deviation 248.902 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 104 | 4.524 pmol/L | Standard Deviation 475.524 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 4 | 11.564 pmol/L | Standard Deviation 335.096 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 8 | 1.789 pmol/L | Standard Deviation 309.673 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 12 | -21.098 pmol/L | Standard Deviation 254.782 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 20 | -32.561 pmol/L | Standard Deviation 320.382 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 28 | -5.123 pmol/L | Standard Deviation 470.691 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 36 | 36.005 pmol/L | Standard Deviation 538.357 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 44 | 57.373 pmol/L | Standard Deviation 594.125 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 52 | 93.245 pmol/L | Standard Deviation 640.998 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 60 | -18.833 pmol/L | Standard Deviation 441.131 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 68 | 39.794 pmol/L | Standard Deviation 581.616 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 76 | 25.291 pmol/L | Standard Deviation 627.834 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 84 | 93.647 pmol/L | Standard Deviation 753.265 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 92 | 1.011 pmol/L | Standard Deviation 474.434 |
| Placebo | Change From BL to Each Study Visit in Serum Ferritin | Week 100 | 30.829 pmol/L | Standard Deviation 514.823 |
Secondary
Change From BL to Each Study Visit in Serum HbA1c Level
HbA1c was measured at each timepoint and presented in 'fraction of 1' unit by dividing the values in percentage by 100, in order to fit for CDISC (Clinical Data Interchange Standards Consortium) standard terminology. Changes from baseline to each timepoint were reported in unit 'fraction of 1'. Baseline was assessed on Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time frame: Baseline and weeks 12, 28, 36, 44, 60, 84, 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Study Visit in Serum HbA1c Level | Week 36 | 0.0011 Fraction of 1 | Standard Deviation 0.0098 |
| Roxadustat | Change From BL to Each Study Visit in Serum HbA1c Level | Week 60 | 0.0009 Fraction of 1 | Standard Deviation 0.0073 |
| Roxadustat | Change From BL to Each Study Visit in Serum HbA1c Level | Week 28 | 0.0006 Fraction of 1 | Standard Deviation 0.0086 |
| Roxadustat | Change From BL to Each Study Visit in Serum HbA1c Level | Week 84 | 0.0028 Fraction of 1 | Standard Deviation 0.0085 |
| Roxadustat | Change From BL to Each Study Visit in Serum HbA1c Level | Week 44 | 0.0018 Fraction of 1 | Standard Deviation 0.0081 |
| Roxadustat | Change From BL to Each Study Visit in Serum HbA1c Level | Week 104 | 0.0014 Fraction of 1 | Standard Deviation 0.0073 |
| Roxadustat | Change From BL to Each Study Visit in Serum HbA1c Level | Week 12 | 0.0007 Fraction of 1 | Standard Deviation 0.0064 |
| Placebo | Change From BL to Each Study Visit in Serum HbA1c Level | Week 104 | 0.0004 Fraction of 1 | Standard Deviation 0.0059 |
| Placebo | Change From BL to Each Study Visit in Serum HbA1c Level | Week 12 | -0.0001 Fraction of 1 | Standard Deviation 0.0061 |
| Placebo | Change From BL to Each Study Visit in Serum HbA1c Level | Week 28 | 0.0008 Fraction of 1 | Standard Deviation 0.0091 |
| Placebo | Change From BL to Each Study Visit in Serum HbA1c Level | Week 36 | 0.0007 Fraction of 1 | Standard Deviation 0.0075 |
| Placebo | Change From BL to Each Study Visit in Serum HbA1c Level | Week 44 | -0.0002 Fraction of 1 | Standard Deviation 0.0074 |
| Placebo | Change From BL to Each Study Visit in Serum HbA1c Level | Week 60 | 0.0012 Fraction of 1 | Standard Deviation 0.008 |
| Placebo | Change From BL to Each Study Visit in Serum HbA1c Level | Week 84 | 0.0022 Fraction of 1 | Standard Deviation 0.0111 |
Secondary
Change From BL to Each Study Visit in Serum Hepcidin
Baseline was assessed on 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
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Study Visit in Serum Hepcidin | Week 36 | -12.981 ug/L | Standard Deviation 32.351 |
| Roxadustat | Change From BL to Each Study Visit in Serum Hepcidin | Week 12 | -17.369 ug/L | Standard Deviation 31.572 |
| Roxadustat | Change From BL to Each Study Visit in Serum Hepcidin | Week 52 | -12.274 ug/L | Standard Deviation 37.445 |
| Roxadustat | Change From BL to Each Study Visit in Serum Hepcidin | Week 4 | -19.835 ug/L | Standard Deviation 29.765 |
| Roxadustat | Change From BL to Each Study Visit in Serum Hepcidin | Week 104 | -10.051 ug/L | Standard Deviation 33.671 |
| Roxadustat | Change From BL to Each Study Visit in Serum Hepcidin | Week 20 | -10.684 ug/L | Standard Deviation 35.858 |
| Placebo | Change From BL to Each Study Visit in Serum Hepcidin | Week 104 | -7.436 ug/L | Standard Deviation 22.923 |
| Placebo | Change From BL to Each Study Visit in Serum Hepcidin | Week 4 | 1.748 ug/L | Standard Deviation 35.368 |
| Placebo | Change From BL to Each Study Visit in Serum Hepcidin | Week 12 | 0.971 ug/L | Standard Deviation 33.952 |
| Placebo | Change From BL to Each Study Visit in Serum Hepcidin | Week 36 | 0.803 ug/L | Standard Deviation 39.816 |
| Placebo | Change From BL to Each Study Visit in Serum Hepcidin | Week 52 | 2.025 ug/L | Standard Deviation 40.678 |
| Placebo | Change From BL to Each Study Visit in Serum Hepcidin | Week 20 | -1.879 ug/L | Standard Deviation 30.661 |
Secondary
Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT)
Baseline was assessed on 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
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 28 | -1.8 Percentage saturated | Standard Deviation 13.8 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 60 | -0.6 Percentage saturated | Standard Deviation 14.1 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 8 | -5.7 Percentage saturated | Standard Deviation 11.7 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 68 | -2.2 Percentage saturated | Standard Deviation 13.1 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 36 | -1.6 Percentage saturated | Standard Deviation 13.6 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 76 | -2.6 Percentage saturated | Standard Deviation 13.8 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 4 | -7.4 Percentage saturated | Standard Deviation 11.7 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 84 | -3.4 Percentage saturated | Standard Deviation 13.3 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 44 | -0.2 Percentage saturated | Standard Deviation 14 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 92 | -1.9 Percentage saturated | Standard Deviation 13.2 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 20 | -1.1 Percentage saturated | Standard Deviation 13.4 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 100 | 0.0 Percentage saturated | Standard Deviation 13.4 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 52 | -0.7 Percentage saturated | Standard Deviation 13.6 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 104 | -0.4 Percentage saturated | Standard Deviation 12.6 |
| Roxadustat | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 12 | -4.6 Percentage saturated | Standard Deviation 13.5 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 104 | 0.0 Percentage saturated | Standard Deviation 12.3 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 12 | -0.7 Percentage saturated | Standard Deviation 11.5 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 4 | 0.7 Percentage saturated | Standard Deviation 11.4 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 8 | -0.4 Percentage saturated | Standard Deviation 13 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 20 | -0.3 Percentage saturated | Standard Deviation 11.5 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 28 | 0.8 Percentage saturated | Standard Deviation 13.2 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 36 | 1.1 Percentage saturated | Standard Deviation 14.6 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 44 | 1.0 Percentage saturated | Standard Deviation 16 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 52 | 0.0 Percentage saturated | Standard Deviation 16.3 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 60 | -2.7 Percentage saturated | Standard Deviation 13.9 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 68 | -3.3 Percentage saturated | Standard Deviation 12.3 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 76 | -1.7 Percentage saturated | Standard Deviation 13.9 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 84 | -3.6 Percentage saturated | Standard Deviation 13.8 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 92 | -1.8 Percentage saturated | Standard Deviation 12.8 |
| Placebo | Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) | Week 100 | 0.7 Percentage saturated | Standard Deviation 12 |
Secondary
Change From BL to the Average Value of Weeks 12-28 in Anemia Subscale (Ans) of Functional Assessment of Cancer Therapy (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.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL to the Average Value of Weeks 12-28 in Anemia Subscale (Ans) of Functional Assessment of Cancer Therapy (FACT-An) Score | 4.470 Units on a Scale |
| Placebo | Change From BL to the Average Value of Weeks 12-28 in Anemia Subscale (Ans) of Functional Assessment of Cancer Therapy (FACT-An) Score | 2.766 Units on a Scale |
Comparison: A Mixed Model of Repeated Measures was applied using the visits up to week 28. The model includes treatment, visit (week 8, week 12 and week 28), visit by treatment interaction, region and history of CV disease as fixed class factors and baseline FACT-An Ans, baseline Hb, baseline eGFR as continuous covariates. Baseline FACT-An Ans is defined as the FACT-An Ans value on day 1.p-value: =0.04795% CI: [0.02, 3.38]Mixed Models Analysis
Secondary
Change From BL to the Average Value of Weeks 12-28 in Overall Work Impairment Due to Anaemic Symptoms
Work productivity and activity impairment: anemic symptoms (WPAI:ANS) questionnaire version 2 was used to measure work and activity impairment during the last seven days due to anemia. It is self-assessed questionnaire which consists of 6 questions covering work and daily activities. Questions include asking if participant is working, how many hours the person missed work due to anemic symptoms, how many hours the person missed work due to other reasons, how many hours participant actually worked and how the anemic symptoms impacted their productivity and ability to do daily activities. For the last 2 questions, they were scored from 0-10 with 0 identifying no effect on work and 10 completely prevented from working. Overall work impairment due to ANS was calculated as 100 x Q2/(Q2+Q4)+\[(1-Q2/(Q2+Q4))x(Q5/10)\]. Scores were calculated with the formula to derive the overall work impairment on each timepoints in percentage, and then changes of the percentage from baseline are reported.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Change From BL to the Average Value of Weeks 12-28 in Overall Work Impairment Due to Anaemic Symptoms | -5.965 Percentage of work impairment | Standard Deviation 21.856 |
| Placebo | Change From BL to the Average Value of Weeks 12-28 in Overall Work Impairment Due to Anaemic Symptoms | -4.230 Percentage of work impairment | Standard Deviation 23.679 |
Secondary
Change From BL to the Average Value of Weeks 12-28 in Quality of Life (QoL) SF-36 Physical Component Score (PCS)
The 36-Item short-form health survey (SF-36) is a multi-purpose survey with 36 questions. It provides an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. For each scale scores range from 0-100. The physical component score was calculated based on the results of the SF-36 scores. Higher scores indicate better health status.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL to the Average Value of Weeks 12-28 in Quality of Life (QoL) SF-36 Physical Component Score (PCS) | 1.842 Units on a Scale |
| Placebo | Change From BL to the Average Value of Weeks 12-28 in Quality of Life (QoL) SF-36 Physical Component Score (PCS) | 1.468 Units on a Scale |
Comparison: The Mixed Model of Repeated Measures included treatment, visit (week 8, week 12 and week 28), visit by treatment interaction, region and history of CV disease as fixed class factors and baseline SF-36 PCS, baseline Hb, baseline eGFR as continuous covariates.p-value: =0.47595% CI: [-0.65, 1.4]Mixed Models Analysis
Secondary
Change From BL to the Average Value of Weeks 12-28 in the Euroqol Questionnaire - 5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score
The Euroqol Questionnaire - 5 Dimensions 5 Levels (EQ-5D 5L) is a self-reported questionnaire. The EQ-5D 5L is used as a measure of respondents' Health Related Quality of Life (HRQoL). The EQ-5D 5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The EQ-5D 5L descriptive system comprises of 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 answers are labeled 'Best imaginable health state' and 'Worst imaginable health state' with higher scores for higher HRQoL.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Change From BL to the Average Value of Weeks 12-28 in the Euroqol Questionnaire - 5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score | 5.390 Units on a Scale | Standard Deviation 17.278 |
| Placebo | Change From BL to the Average Value of Weeks 12-28 in the Euroqol Questionnaire - 5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score | 0.990 Units on a Scale | Standard Deviation 15.859 |
Secondary
Change From BL to the Average Value of Weeks 12-28 in Total FACT-An Score
Baseline FACT-An Total Score was defined as the FACT-An Total score 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
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL to the Average Value of Weeks 12-28 in Total FACT-An Score | 5.777 Units on a Scale |
| Placebo | Change From BL to the Average Value of Weeks 12-28 in Total FACT-An Score | 3.691 Units on a Scale |
Comparison: A Mixed Model of Repeated Measures was applied using the visits up to week 28. The results were based on the estimated difference between the two treatment arms overall mean effect during week 12 to 28 period based on this MMRM model.The model includes treatment, visit (week8, week12 and week28), visit by treatment interaction, region and history of CV disease as fixed class factors and baseline FACT-An Total Score, baseline Hb, baseline eGFR as continuous covariates.p-value: =0.22595% CI: [-1.29, 5.46]Mixed Models Analysis
Secondary
Hb Change From BL to Each Post-Dosing Time Point
All scheduled and unscheduled hemoglobin values that belong to each visit window were taken into account using one value per analysis window. 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 (day 1) and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 2 | 0.977 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 44 | 1.977 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 18 | 2.087 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 48 | 1.695 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 10 | 2.129 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 52 | 1.939 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 20 | 2.191 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 56 | 1.725 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 6 | 1.927 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 60 | 1.988 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 22 | 1.873 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 64 | 1.637 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 12 | 2.412 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 68 | 1.913 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 24 | 1.802 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 72 | 1.765 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 4 | 1.591 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 76 | 1.859 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 28 | 1.996 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 80 | 1.752 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 14 | 2.214 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 84 | 1.854 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 32 | 1.911 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 88 | 1.570 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 8 | 2.236 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 92 | 1.800 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 36 | 2.100 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 96 | 1.701 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 16 | 2.365 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 100 | 1.763 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 40 | 1.887 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 104 | 1.857 g/dL |
| Roxadustat | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 1 | 0.390 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 104 | 0.511 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 1 | -0.006 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 2 | 0.039 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 4 | 0.119 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 6 | 0.100 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 8 | 0.178 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 10 | 0.180 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 12 | 0.322 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 14 | 0.163 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 16 | 0.378 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 18 | 0.246 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 20 | 0.367 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 22 | 0.222 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 24 | 0.355 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 28 | 0.435 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 32 | 0.324 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 36 | 0.410 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 40 | 0.241 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 44 | 0.278 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 48 | 0.249 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 52 | 0.298 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 56 | 0.085 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 60 | 0.354 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 64 | 0.233 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 68 | 0.414 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 72 | 0.328 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 76 | 0.674 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 80 | 0.308 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 84 | 0.480 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 88 | 0.399 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 92 | 0.418 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 96 | 0.139 g/dL |
| Placebo | Hb Change From BL to Each Post-Dosing Time Point | Hb Change From BL to Week 100 | 0.315 g/dL |
Comparison: Hb change from BL to week 1. A Mixed Model of Repeated Measures was applied using the visits up to week 104. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [0.29, 0.5]Mixed Models Analysis
Comparison: Hb change from BL to week 2. A Mixed Model of Repeated Measures was applied using the visits up to Week 104. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [0.81, 1.07]Mixed Models Analysis
Comparison: Hb change from BL to week 4. A Mixed Model of Repeated Measures was applied using the visits up to Week 104. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.3, 1.64]Mixed Models Analysis
Comparison: Hb change from BL to week 6. A Mixed Model of Repeated Measures was applied using the visits up to Week 104. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.64, 2.02]Mixed Models Analysis
Comparison: Hb change from BL to week 8. A Mixed Model of Repeated Measures was applied using the visits up to Week 104. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.87, 2.25]Mixed Models Analysis
Comparison: Hb change from BL to week 10. A Mixed Model of Repeated Measures was applied using the visits up to Week 104. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.75, 2.14]Mixed Models Analysis
Comparison: Hb change from BL to week 12. A Mixed Model of Repeated Measures was applied using the visits up to Week 104. The results were based on the estimated difference between the two treatment arms by visit.The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.9, 2.28]Mixed Models Analysis
Comparison: Hb change from BL to week 14. A Mixed Model of Repeated Measures was applied using the visits up to Week 104. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.86, 2.24]Mixed Models Analysis
Comparison: Hb change from BL to week 16. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.79, 2.19]Mixed Models Analysis
Comparison: Hb change from BL to week 18. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.64, 2.05]Mixed Models Analysis
Comparison: Hb change from BL to week 20. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.61, 2.04]Mixed Models Analysis
Comparison: Hb change from BL to week 22. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit.The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.43, 1.87]Mixed Models Analysis
Comparison: Hb change from BL to week 24. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.23, 1.67]Mixed Models Analysis
Comparison: Hb change from BL to week 28. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.34, 1.78]Mixed Models Analysis
Comparison: Hb change From BL to week 32. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.37, 1.81]Mixed Models Analysis
Comparison: Hb Change from BL to week 36. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit.The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.46, 1.92]Mixed Models Analysis
Comparison: Hb change from BL to week 40. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.41, 1.88]Mixed Models Analysis
Comparison: Hb change from BL to week 44. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.45, 1.94]Mixed Models Analysis
Comparison: Hb change From BL to week 48. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.2, 1.69]Mixed Models Analysis
Comparison: Hb change from BL to week 52. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit.The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.39, 1.89]Mixed Models Analysis
Comparison: Hb change from BL to week 56. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit.The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.37, 1.91]Mixed Models Analysis
Comparison: Hb change from BL to week 60. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.33, 1.94]Mixed Models Analysis
Comparison: Hb change from BL to week 64. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.08, 1.73]Mixed Models Analysis
Comparison: Hb change From BL to week 68. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.18, 1.82]Mixed Models Analysis
Comparison: Hb change from BL to week 72. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.1, 1.78]Mixed Models Analysis
Comparison: Hb change from BL to week 76. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [0.83, 1.54]Mixed Models Analysis
Comparison: Hb change from BL to week 80. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.11, 1.78]Mixed Models Analysis
Comparison: Hb change from BL to week 84. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [0.99, 1.75]Mixed Models Analysis
Comparison: Hb change from BL to week 88. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [0.79, 1.55]Mixed Models Analysis
Comparison: Hb change from BL to week 92. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [0.98, 1.78]Mixed Models Analysis
Comparison: Hb change from BL to week 96. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.15, 1.97]Mixed Models Analysis
Comparison: Hb change from BL to week 100. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.06, 1.83]Mixed Models Analysis
Comparison: Hb change from BL to week 104. A Mixed Model of Repeated Measures was applied. The results were based on the estimated difference between the two treatment arms by visit. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [0.9, 1.79]Mixed Models Analysis
Secondary
Hb Change From BL to the Average Hb in Weeks 28-36 Without Having Received Rescue Therapy Within 6 Weeks Prior to and During 8-Week Evaluation Period
The Hb values from visit windows at weeks 28, 32 and 36 were used for the calculation of the average of weeks 28 to 36.
Time frame: Baseline and weeks 28 to 36
Population: The analysis population was the full analysis set (FAS), which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Hb Change From BL to the Average Hb in Weeks 28-36 Without Having Received Rescue Therapy Within 6 Weeks Prior to and During 8-Week Evaluation Period | 2.069 g/dL |
| Placebo | Hb Change From BL to the Average Hb in Weeks 28-36 Without Having Received Rescue Therapy Within 6 Weeks Prior to and During 8-Week Evaluation Period | 0.470 g/dL |
Comparison: The model includes treatment, visit, visit by treatment interaction, region and history of CV disease as fixed class factors and baseline Hb, baseline eGFR and baseline Hb by visit interaction as continuous covariates.p-value: <0.00195% CI: [1.41, 1.78]Mixed Models Analysis
Secondary
Hb Change From BL to the Average Hb Value of Weeks 28-36 Regardless of the Use of Rescue Therapy
The Hb values from visit windows from weeks 28 to 36 were used for the calculation of the average regardless 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-dosing).
Time frame: Baseline and weeks 28 to 36
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Hb Change From BL to the Average Hb Value of Weeks 28-36 Regardless of the Use of Rescue Therapy | 2.013 g/dL |
| Placebo | Hb Change From BL to the Average Hb Value of Weeks 28-36 Regardless of the Use of Rescue Therapy | 0.399 g/dL |
Comparison: Change from baseline to average Hb weeks 28-36. A Mixed Model of Repeated Measures was applied using the visits up to week 36. The results were based on the estimated difference between the two treatment arms overall mean effect during week 28 to 36 period based on this MMRM model. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.42, 1.81]Mixed Models Analysis
Secondary
Hb Change From BL to the Average Hb Value of Weeks 44-52 Regardless of the Use of Rescue Therapy
The Hb values from visit windows from weeks 44 to 52 were used for the calculation of the average regardless 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-dosing).
Time frame: Baseline and weeks 44 to 52
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Hb Change From BL to the Average Hb Value of Weeks 44-52 Regardless of the Use of Rescue Therapy | 1.886 g/dL |
| Placebo | Hb Change From BL to the Average Hb Value of Weeks 44-52 Regardless of the Use of Rescue Therapy | 0.292 g/dL |
Comparison: Change from baseline to average Hb weeks 44-52. A Mixed Model of Repeated Measures was applied using the visits up to week 52. The results were based on the estimated difference between the two treatment arms overall mean effect during week 44 to 52 period based on this MMRM model. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.38, 1.81]Mixed Models Analysis
Secondary
Hb Change From BL to the Average Hb Value of Weeks 96-104 Regardless of the Use of Rescue Therapy
The Hb values from visit windows from weeks 96 to 104 were used for the calculation of the average regardless 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-dosing).
Time frame: Baseline and weeks 96 to 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Hb Change From BL to the Average Hb Value of Weeks 96-104 Regardless of the Use of Rescue Therapy | 1.779 g/dL |
| Placebo | Hb Change From BL to the Average Hb Value of Weeks 96-104 Regardless of the Use of Rescue Therapy | 0.327 g/dL |
Comparison: Change from BL to average Hb weeks 96-104. A Mixed Model of Repeated Measures was applied using the visits up to week 104. The results were based on the estimated difference between the two treatment arms overall mean effect during week 96 to 104 period based on this MMRM model. The model included treatment arm, region, CV history, visits and visit by treatment as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: <0.00195% CI: [1.1, 1.8]Mixed Models Analysis
Secondary
Mean Monthly Number of RBC Packs
During efficacy emergent period, the mean monthly number of RBC packs was calculated as the sum of 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 7 days after the analysis date of last dose or EOT visit, whichever occured first. In case of missing number of packs, values were estimated based on 1 unit for packed cells = 250 mL or 1 unit for whole blood = 500 mL. Participants without RBC transfusion were included with a value of zero. No estimation if values were missing.
Time frame: Baseline to week 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Mean Monthly Number of RBC Packs | 0.041 RBC Packs per 28 days | Standard Deviation 0.397 |
| Placebo | Mean Monthly Number of RBC Packs | 0.089 RBC Packs per 28 days | Standard Deviation 0.243 |
Comparison: The Analysis of Covariance (ANCOVA) model was applied including treatment as fixed factor, region and history of CV disease as class factors and baseline Hb, baseline eGFR as continuous covariates.p-value: =0.12895% CI: [-0.1, 0.01]ANCOVA
Secondary
Mean Monthly Volume of Blood Transfused
During efficacy emergent period, the mean monthly volume of blood transfused was calculated as the sum of blood volume 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 7 days after the analysis date of last dose or EOT visit, whichever occurred first. The mean monthly volume transfused was calculated as the sum of the volume transfused between the first dose and up to the last dose in the period divided by duration (in days) and multiplied by 28 days. Participants without RBC transfusion were included with a value of zero.
Time frame: Baseline to week 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Mean Monthly Volume of Blood Transfused | 11.331 Milliliters (ml) per 28 days | Standard Deviation 106.624 |
| Placebo | Mean Monthly Volume of Blood Transfused | 22.596 Milliliters (ml) per 28 days | Standard Deviation 60.666 |
Comparison: The Analysis of Covariance (ANCOVA) model was applied included treatment arm, region, CV history as categorical variables and baseline Hb and baseline eGFR as continuous variables.p-value: =0.18395% CI: [-25.81, 4.95]ANCOVA
Secondary
Number of Days of Hospitalization Per Patient Exposure Year (PEY)
The sum of the durations of all hospitalizations in days was adjusted for the duration of exposure. Derived only for participants with at least one hospitalization. The number of days of hospitalization per PEY was calculated as the sum of the durations of all hospitalizations in days \[Minimum (Date of discharge, End of Efficacy Emergent Period) - Date of admission + 1\] / \[Duration of Efficacy Emergent Period in days / 365.25\]. Participants can have more than one hospitalization.
Time frame: Baseline to week 104
Population: The analysis population was the FAS, which consisted of participants with hospitalizations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Number of Days of Hospitalization Per Patient Exposure Year (PEY) | 14.567 Number of days per PEY | Standard Deviation 29.214 |
| Placebo | Number of Days of Hospitalization Per Patient Exposure Year (PEY) | 15.885 Number of days per PEY | Standard Deviation 30.224 |
Secondary
Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 28-36 Without Use of Rescue Therapy
The percentage of Hb values measured during weeks 28-36 within 10.0 -12.0 g/dL, without having received rescue therapy within 6 weeks prior to and during the 8-week evaluation period is reported.
Time frame: Baseline and weeks 28 to 36
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 28-36 Without Use of Rescue Therapy | 64.18 Percentage of Hb values | Standard Deviation 32.9 |
| Placebo | Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 28-36 Without Use of Rescue Therapy | 34.20 Percentage of Hb values | Standard Deviation 39.47 |
Secondary
Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 44-52 Without Use of Rescue Therapy
The percentage of Hb values measured during weeks 44-52 with values within 10.0 - 12.0 g/dL, without having received rescue therapy within 6 weeks prior to and during the 8-week evaluation period is reported.
Time frame: Baseline and weeks 44 to 52
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 44-52 Without Use of Rescue Therapy | 69.39 Percentage of Hb values | Standard Deviation 32.47 |
| Placebo | Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 44-52 Without Use of Rescue Therapy | 35.45 Percentage of Hb values | Standard Deviation 41.75 |
Secondary
Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 96-104 Without Use of Rescue Therapy
The percentage of Hb values measured during weeks 96-104 within 10.0 -12.0 g/dL, without having received rescue therapy within 6 weeks prior to and during the 8-week evaluation period is reported.
Time frame: Baseline and weeks 96 to 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 96-104 Without Use of Rescue Therapy | 64.65 Percentage of Hb values | Standard Deviation 37.16 |
| Placebo | Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 96-104 Without Use of Rescue Therapy | 40.63 Percentage of Hb values | Standard Deviation 44.39 |
Secondary
Percentage of Participants in Each Category in Patients' Global Impression of Change (PGIC)
The Patients' Global Impression of Change (PGIC) is a participant-rated instrument that measures change in participants overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).
Time frame: Week 12 to 28
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Percentage of Participants in Each Category in Patients' Global Impression of Change (PGIC) | Week 12 [Very much improved + Much improved] | 41.2 Percentage of Participants |
| Roxadustat | Percentage of Participants in Each Category in Patients' Global Impression of Change (PGIC) | Week 28 [Very much improved + Much improved] | 46.4 Percentage of Participants |
| Placebo | Percentage of Participants in Each Category in Patients' Global Impression of Change (PGIC) | Week 12 [Very much improved + Much improved] | 18.9 Percentage of Participants |
| Placebo | Percentage of Participants in Each Category in Patients' Global Impression of Change (PGIC) | Week 28 [Very much improved + Much improved] | 28.6 Percentage of Participants |
Secondary
Percentage of Participants Who Have Achieved Antihypertensive Treatment Goal in CKD Participants Over Weeks 12-28
Occurrence of achieved antihypertensive treatment goal was defined as the average SBP \< 130 mmHg and the average DBP \< 80 mmHg over the period of weeks 12-28. Participants without any blood pressure measurement were excluded.
Time frame: Weeks 12 to 28
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Percentage of Participants Who Have Achieved Antihypertensive Treatment Goal in CKD Participants Over Weeks 12-28 | Yes | 25.6 Percentage of Participants |
| Roxadustat | Percentage of Participants Who Have Achieved Antihypertensive Treatment Goal in CKD Participants Over Weeks 12-28 | No | 74.4 Percentage of Participants |
| Placebo | Percentage of Participants Who Have Achieved Antihypertensive Treatment Goal in CKD Participants Over Weeks 12-28 | Yes | 28.0 Percentage of Participants |
| Placebo | Percentage of Participants Who Have Achieved Antihypertensive Treatment Goal in CKD Participants Over Weeks 12-28 | No | 72.0 Percentage of Participants |
Secondary
Percentage of Participants With Mean LDL Cholesterol <100 mg/dL Calculated Over Weeks 12 to 28
Mean LDL cholesterol \<100 mg/dL over weeks 12 to 28 was defined as a binary variable (Yes/No), where Yes was defined as mean LDL cholesterol \<100 mg/dL over weeks 12 to 28. Participants without any LDL value within this duration were excluded.
Time frame: Weeks 12 to 28
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Percentage of Participants With Mean LDL Cholesterol <100 mg/dL Calculated Over Weeks 12 to 28 | Yes (Regardless of fasting status) | 62.9 Percentage of Participants |
| Roxadustat | Percentage of Participants With Mean LDL Cholesterol <100 mg/dL Calculated Over Weeks 12 to 28 | No (Regardless of fasting status) | 37.1 Percentage of Participants |
| Placebo | Percentage of Participants With Mean LDL Cholesterol <100 mg/dL Calculated Over Weeks 12 to 28 | Yes (Regardless of fasting status) | 41.1 Percentage of Participants |
| Placebo | Percentage of Participants With Mean LDL Cholesterol <100 mg/dL Calculated Over Weeks 12 to 28 | No (Regardless of fasting status) | 58.9 Percentage of Participants |
Secondary
Rate of Progression of CKD Measured by Annualized Estimated Glomerular Filtration Rate (eGFR) Slope Over Time
Annualized eGFR slope over time was estimated by a random slopes and intercepts model using all available eGFR values (one baseline and all post-treatment values up to EOT period or start of dialysis adjusted on baseline Hb, region, CV history at baseline and the interaction terms (baseline eGFR by timepoint and baseline Hb by timepoint). All assessments collected after initiation of chronic dialysis (acute or chronic) are excluded from the analysis. Baseline assessment was the assessment from day 1 visit. If this value was missing, the value from screening visit was used.
Time frame: Baseline to week 108
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Rate of Progression of CKD Measured by Annualized Estimated Glomerular Filtration Rate (eGFR) Slope Over Time | -2.65 ml/min per 1.73 m^2 per year |
| Placebo | Rate of Progression of CKD Measured by Annualized Estimated Glomerular Filtration Rate (eGFR) Slope Over Time | -3.24 ml/min per 1.73 m^2 per year |
Comparison: Annualized eGFR slope over time was estimated by a random slopes and intercepts model using all available eGFR values adjusted on baseline Hb, region, CV history at Baseline and the interaction terms.p-value: =0.31695% CI: [-0.57, 1.75]Mixed Models Analysis
Secondary
Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint
Hb response was measured as Yes or No; Yes was defined as Hb ≥11.0 g/dL and Hb increase from baseline by ≥ 1.0 g/dL, for participants with baseline Hb \> 8.0 g/dL; or Hb increase from baseline by ≥ 2.0 g/dL, for participants with baseline Hb ≤ 8.0 g/dL. For a participant without rescue therapy before Hb response (defined in 1 primary outcome), the time to achieve Hb response was calculated (in weeks) as: (First event date - Analysis date of first dose intake + 1) / 7 where First event date was defined as First date of both values that met the criteria for response. Participants who discontinued or received rescue therapy prior to the first Hb response or before the second consecutive Hb value defined as a response were classified as non responders and were censored at week 24 or end of efficacy emergent period, whichever came first. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion.
Time frame: Baseline to week 24
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint | Week 4 | 26.0 Percentage of participants |
| Roxadustat | Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint | Week 8 | 59.8 Percentage of participants |
| Roxadustat | Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint | Week 16 | 83.4 Percentage of participants |
| Roxadustat | Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint | Week 24 | 89.1 Percentage of participants |
| Placebo | Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint | Week 24 | 11.6 Percentage of participants |
| Placebo | Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint | Week 4 | 3.5 Percentage of participants |
| Placebo | Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint | Week 16 | 9.4 Percentage of participants |
| Placebo | Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint | Week 8 | 6.2 Percentage of participants |
Comparison: Time to Achieve the First Hb Response. Hazard ratio was calculated using stratified Cox Proportional Hazards Regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: <0.00195% CI: [11.98, 30.15]Regression, Cox
Secondary
Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant
All eGFR values collected during the safety emergent period are considered, excluding those collected on or after initiation of dialysis (acute or chronic). The First event date was defined as First occurrence of 40% decrease in eGFR from baseline, first occurrence of chronic dialysis or renal transplant (whichever occurred first and Analysis date of first dose intake was defined as date of first study drug dose intake collected on day 1 visit. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the analysis date of last dose or end of study (EOS), whichever occurred first. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. The data evaluated until the safety emergent period, which was defined as the evaluation period from analysis date of first drug intake up to 28 days after the analysis last dose, and results were presented for every 6 months up to 2 years.
Time frame: Baseline and year 0.5, year 1, year 1.5 and year 2
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Years 0.5 | 20.7 Percentage of participants |
| Roxadustat | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Years 1 | 44.4 Percentage of participants |
| Roxadustat | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Years 1.5 | 54.6 Percentage of participants |
| Roxadustat | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Years 2 | 64.5 Percentage of participants |
| Placebo | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Years 2 | 67.0 Percentage of participants |
| Placebo | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Years 0.5 | 22.3 Percentage of participants |
| Placebo | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Years 1.5 | 62.8 Percentage of participants |
| Placebo | Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant | Years 1 | 44.0 Percentage of participants |
Comparison: Hazard ratio was calculated using stratified Cox Proportional Hazards Regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: =0.43995% CI: [0.7, 1.16]Regression, Cox
Secondary
Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death)
CKD progression was defined as date of occurrence of chronic dialysis or date of renal transplant or doubled serum creatinine or date of death, whichever came first. The time to CKD progression was calculated (in years) as (First event date - Analysis date of first dose intake + 1) / 365.25. First event date was defined as first occurrence of serum creatinine being doubled compared with baseline, first occurrence of chronic dialysis or renal transplant, occurrence of participants who died (whichever occurred first). Analysis date of first dose intake was defined as date of first study drug dose intake collected on day 1 visit. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. The data evaluated until the safety emergent period, which was defined as the evaluation period from analysis date of first drug intake up to 28 days after the analysis last dose, and results were presented for every 6 months up to 2 years.
Time frame: Baseline and year 0.5, year 1, year 1.5 and year 2
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Years 0.5 | 20.5 Percentage of participants |
| Roxadustat | Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Years 1 | 40.3 Percentage of participants |
| Roxadustat | Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Years 1.5 | 50.2 Percentage of participants |
| Roxadustat | Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Years 2 | 58.9 Percentage of participants |
| Placebo | Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Years 2 | 61.1 Percentage of participants |
| Placebo | Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Years 0.5 | 20.0 Percentage of participants |
| Placebo | Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Years 1.5 | 50.5 Percentage of participants |
| Placebo | Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) | Years 1 | 38.3 Percentage of participants |
Comparison: Time to CKD progression. Hazard ratio was calculated using stratified Cox Proportional Hazards Regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: =0.97295% CI: [0.76, 1.3]Regression, Cox
Secondary
Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline
The endpoint was defined as time to doubling serum creatinine or chronic dialysis or renal transplant what ever came first. Time to event was defined as (First event date - Analysis date of first dose intake + 1) / 365.25. First event date was defined as date of dialysis or date of renal transplant (whichever occurred first) and analysis date of first dose intake was defined as date of first study drug dose intake collected on day 1 visit. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. The data evaluated until the safety emergent period, which was defined as the evaluation period from analysis date of first drug intake up to 28 days after the analysis last dose, and results were presented for every 6 months up to 2 years.
Time frame: Baseline and year 0.5, year 1, year 1.5 and year 2
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Years 0.5 | 17.4 Percentage of participants |
| Roxadustat | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Years 1 | 36.8 Percentage of participants |
| Roxadustat | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Years 1.5 | 47.3 Percentage of participants |
| Roxadustat | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Years 2 | 55.0 Percentage of participants |
| Placebo | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Years 2 | 54.7 Percentage of participants |
| Placebo | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Years 0.5 | 17.8 Percentage of participants |
| Placebo | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Years 1.5 | 48.2 Percentage of participants |
| Placebo | Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline | Years 1 | 35.4 Percentage of participants |
Comparison: Time to doubling of serum Creatinine. Hazard ratio was calculated using stratified Cox Proportional Hazards Regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: =0.97395% CI: [0.75, 1.32]Regression, Cox
Secondary
Time to First Hospitalization
Time to first hospitalization was defined in years as the First event date during the Efficacy Emergent Period - (Analysis date of first dose intake +1)/365.25. The first event date was defined as the Date of first admission. The Efficacy Emergent Period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or EOT visit, whichever occured first. Analysis date of first dose intake was defined as the date of first study drug intake collected on day 1 visit. For participants who experienced more than one hospitalization, only their first event following study treatment was used. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion.
Time frame: Baseline to week 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Hospitalization | Year 1 | 49.9 Percentage of participants |
| Roxadustat | Time to First Hospitalization | Year 0.5 | 32.2 Percentage of participants |
| Roxadustat | Time to First Hospitalization | Year 2 | NA Percentage of participants |
| Roxadustat | Time to First Hospitalization | Year 1.5 | 62.1 Percentage of participants |
| Placebo | Time to First Hospitalization | Year 2 | 67.8 Percentage of participants |
| Placebo | Time to First Hospitalization | Year 0.5 | 39.8 Percentage of participants |
| Placebo | Time to First Hospitalization | Year 1 | 49.3 Percentage of participants |
| Placebo | Time to First Hospitalization | Year 1.5 | 64.0 Percentage of participants |
Comparison: Hazard ratio was calculated using stratified Cox Proportional Hazards Regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: =0.64395% CI: [0.74, 1.2]Regression, Cox
Secondary
Time to First Occurrence of Hypertension
Occurrence of hypertension was defined as SBP increase from BL ≥20 mmHg and SBP \>170 mmHg or DBP increase from BL ≥15 mmHg and DBP ≥110 mmHg. Time to first occurrence of hypertension was defined as first date where SBP criterion or DBP criterion is met, whichever occurred first. Data was analysed using Kaplan-Meier estimate for cumulative proportion.
Time frame: Baseline and year 0.5, year 1, year 1.5 and year 2
Population: The analysis population was the PPS, which consisted of all FAS participants who did not meet any reasons for exclusion from the PPS and had all available data at all time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Occurrence of Hypertension | Year 0.5 | 11.4 Percentage of participants |
| Roxadustat | Time to First Occurrence of Hypertension | Year 1 | 14.8 Percentage of participants |
| Roxadustat | Time to First Occurrence of Hypertension | Year 1.5 | 17.5 Percentage of participants |
| Roxadustat | Time to First Occurrence of Hypertension | Year 2 | 18.5 Percentage of participants |
| Placebo | Time to First Occurrence of Hypertension | Year 2 | 12.5 Percentage of participants |
| Placebo | Time to First Occurrence of Hypertension | Year 0.5 | 10.1 Percentage of participants |
| Placebo | Time to First Occurrence of Hypertension | Year 1.5 | 12.5 Percentage of participants |
| Placebo | Time to First Occurrence of Hypertension | Year 1 | 12.5 Percentage of participants |
Comparison: Hazard ratio was calculated using stratified Cox Proportional Hazards Regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: =0.33495% CI: [0.77, 2.16]Regression, Cox
Secondary
Time to First Use of ESA Rescue Therapy
Time to First Use of ESA Rescue Therapy during efficacy emergent period. For participants with use of ESA, the time to first use of ESA was calculated as (First event date - Analysis date of first dose intake + 1) / 365.25. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or EOT visit, whichever occured first. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. Participants without ESA rescue were censored at the end of treatment.
Time frame: Baseline to week 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Use of ESA Rescue Therapy | Year 0.5 | 1.8 Percentage of participants |
| Roxadustat | Time to First Use of ESA Rescue Therapy | Year 1 | 4.8 Percentage of participants |
| Roxadustat | Time to First Use of ESA Rescue Therapy | Year 1.5 | 6.0 Percentage of participants |
| Roxadustat | Time to First Use of ESA Rescue Therapy | Year 2 | 6.7 Percentage of participants |
| Placebo | Time to First Use of ESA Rescue Therapy | Year 2 | 42.3 Percentage of participants |
| Placebo | Time to First Use of ESA Rescue Therapy | Year 0.5 | 20.4 Percentage of participants |
| Placebo | Time to First Use of ESA Rescue Therapy | Year 1.5 | 42.3 Percentage of participants |
| Placebo | Time to First Use of ESA Rescue Therapy | Year 1 | 36.4 Percentage of participants |
Comparison: Hazard ratio was calculated using stratified Cox Proportional Hazards Regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: <0.00195% CI: [0.06, 0.17]Regression, Cox
Secondary
Time to First Use of IV Iron
Time to first use of IV iron during efficacy emergent period in years. For participants with use of IV iron, the time to first use of IV iron was calculated as (First event date - Analysis date of first dose intake + 1) / 365.25. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or EOT visit, whichever occurred first.Data analysis was completed using Kaplan-Meier estimate for cumulative proportion.
Time frame: Baseline to week 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Use of IV Iron | Year 0.5 | 2.3 Percentage of participants |
| Roxadustat | Time to First Use of IV Iron | Year 1 | 5.3 Percentage of participants |
| Roxadustat | Time to First Use of IV Iron | Year 1.5 | 7.5 Percentage of participants |
| Roxadustat | Time to First Use of IV Iron | Year 2 | 10.6 Percentage of participants |
| Placebo | Time to First Use of IV Iron | Year 2 | 19.1 Percentage of participants |
| Placebo | Time to First Use of IV Iron | Year 0.5 | 6.2 Percentage of participants |
| Placebo | Time to First Use of IV Iron | Year 1.5 | 10.7 Percentage of participants |
| Placebo | Time to First Use of IV Iron | Year 1 | 9.4 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards Regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: =0.04595% CI: [0.29, 0.99]Regression, Cox
Secondary
Time to First Use of RBC Transfusions
Time to First Use of RBC Transfusions during efficacy emergent period. For participants who have experienced more than one RBC transfusion, only their first event following study treatment was used. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or EOT visit, whichever occured first. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion.
Time frame: Baseline to week 104
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Use of RBC Transfusions | Year 0.5 | 2.9 Percentage of participants |
| Roxadustat | Time to First Use of RBC Transfusions | Year 1 | 5.6 Percentage of participants |
| Roxadustat | Time to First Use of RBC Transfusions | Year 1.5 | 12.1 Percentage of participants |
| Roxadustat | Time to First Use of RBC Transfusions | Year 2 | 15.0 Percentage of participants |
| Placebo | Time to First Use of RBC Transfusions | Year 2 | 27.0 Percentage of participants |
| Placebo | Time to First Use of RBC Transfusions | Year 0.5 | 15.2 Percentage of participants |
| Placebo | Time to First Use of RBC Transfusions | Year 1.5 | 21.8 Percentage of participants |
| Placebo | Time to First Use of RBC Transfusions | Year 1 | 20.2 Percentage of participants |
Comparison: Hazard ratio was calculated using stratified Cox Proportional Hazards Regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: <0.00195% CI: [0.21, 0.55]Regression, Cox
Secondary
Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment
Time to first use of rescue therapy in years. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion.
Time frame: Baseline to week 24
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment | Week 6 | 0.8 Percentage of participants |
| Roxadustat | Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment | Week 12 | 2.5 Percentage of participants |
| Roxadustat | Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment | Week 18 | 3.3 Percentage of participants |
| Roxadustat | Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment | Week 24 | 5.5 Percentage of participants |
| Placebo | Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment | Week 24 | 32.1 Percentage of participants |
| Placebo | Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment | Week 6 | 6.0 Percentage of participants |
| Placebo | Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment | Week 18 | 25.3 Percentage of participants |
| Placebo | Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment | Week 12 | 15.8 Percentage of participants |
Comparison: Time to start rescue therapy within first 24 weeks. Hazard ratio was calculated using stratified Cox Proportional Hazards Regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates.p-value: <0.00195% CI: [0.08, 0.23]Regression, Cox
Secondary
Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron)
The time to first use of rescue therapy was calculated (in years) as: (First event date - Analysis date of first dose intake + 1) / 365.25. The First event date was defined as Date of first dose of rescue medication during the efficacy emergent period and Analysis date of first dose intake was defined as date of first study drug dose intake collected on day 1. The Efficacy Emergent Period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or the end of treatment (EOT) visit, whichever occurred first. Data reported was analysed by Kaplan-Meier estimate for cumulative proportion. Medication onset date was the date of the first use of rescue medication.
Time frame: Baseline to week 104 (End of Treatment [EOT])
Population: The analysis population was the FAS, which consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose Hb assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron) | Year 0.5 | 6.1 Percentage of participants |
| Roxadustat | Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron) | Year 1 | 13.0 Percentage of participants |
| Roxadustat | Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron) | Year 1.5 | 22.0 Percentage of participants |
| Roxadustat | Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron) | Year 2 | 26.3 Percentage of participants |
| Placebo | Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron) | Year 2 | 57.8 Percentage of participants |
| Placebo | Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron) | Year 0.5 | 33.3 Percentage of participants |
| Placebo | Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron) | Year 1.5 | 52.5 Percentage of participants |
| Placebo | Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron) | Year 1 | 50.1 Percentage of participants |
Comparison: Hazard ratio was calculated using stratified Cox Proportional Hazards Regression stratifying on CV history and region and adjusting on Hb and eGFR at baseline as continuous covariates. Superiority is declared if the upper bound of the 95% CI is below 1.0.p-value: <0.00195% CI: [0.17, 0.33]Regression, Cox