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Roxadustat in the Treatment of Anemia in End Stage Renal Disease (ESRD) Patients on Stable Dialysis (Pyrenees)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02278341
Recruitment Status : Completed
First Posted : October 30, 2014
Last Update Posted : February 10, 2020
Sponsor:
Collaborator:
FibroGen
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )

Brief Summary:
This study was conducted to explore a new therapy for anemia in participants with end stage renal disease (ESRD) on dialysis. Anemia is a reduced number of red blood cells or hemoglobin. Hemoglobin (which contains iron) is important for the transport of oxygen in your blood. The purpose of this study was to evaluate if roxadustat is effective and safe in the maintenance treatment of anemia in ESRD participants on stable dialysis. Roxadustat was compared to epoetin alfa and darbepoetin alfa, commercially available medicines for treatment of anemia.

Condition or disease Intervention/treatment Phase
Anemia End Stage Renal Disease (ESRD) Drug: Roxadustat Drug: Epoetin alfa Drug: Darbepoetin alfa Phase 3

Detailed Description:

This study consisted of three study periods as follows:

  • Screening Period: up to 6 weeks
  • Treatment Period: a minimum of 52 weeks up to a maximum of 104 weeks
  • Follow-up Period: 4 weeks

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 838 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Open-Label, Active-Controlled Study to Evaluate the Efficacy and Safety of Roxadustat in the Maintenance Treatment of Anemia in End Stage Renal Disease Patients on Stable Dialysis
Actual Study Start Date : November 21, 2014
Actual Primary Completion Date : June 8, 2017
Actual Study Completion Date : July 6, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Roxadustat
Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Drug: Roxadustat
Participants received initial dose of roxadustat orally as a tablet in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
Other Names:
  • ASP1517
  • FG-4592

Active Comparator: ESA (Erythropoiesis Stimulating Agent) treatment
Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from the epoetin alfa to darbepoetin alfa or vice versa.
Drug: Epoetin alfa
Participants received epoetin alfa via intravenous or subcutaneous injection, once a week, twice a week, or three times a week (TIW). Epoetin alfa dosage was adjusted to maintain Hb level within the target range. Dosing of epoetin alfa was per UK SmPC of Eprex®. Participants received IV iron supplementation according to the standard of care.
Other Name: Eprex

Drug: Darbepoetin alfa
Participants received darbepoetin alfa via intravenous or subcutaneous injection, once a week or once every other week. Darbepoetin alfa dosage was adjusted to maintain Hb level within the target range. Dosing of darbepoetin alfa was per EU SmPC of Aranesp®. Participants received IV iron supplementation according to the standard of care.
Other Name: Aranesp




Primary Outcome Measures :
  1. Change From Baseline (BL) to the Average Hemoglobin (Hb) in Weeks 28-36 Without Rescue Therapy [EU (EMA)] [ Time Frame: Baseline and weeks 28 to 36 ]
    Baseline Hb was defined as the mean of four central laboratory Hb values; four latest Hb values prior or on the same date as the first study drug intake. For participants who did not have an available Hb value during the week 28-36 period, imputation rules were applied. For analyses without rescue therapy, participants who used rescue therapy after the initiation of rescue therapy were set to missing for 6 weeks from the start date of rescue therapy. If no Hb value was available, an imputation technique was used, with the mean of all available values from Day 1 to minimum (End of Efficacy Emergent Period) carried forward.

  2. Change From BL to the Average Hb in Weeks 28 to 52 Regardless of Rescue Therapy [US (FDA)] [ Time Frame: Baseline and weeks 28 to 52 ]
    Baseline Hb was defined as the mean of four central laboratory Hb values: four latest Hb values prior or on the same date as first study drug intake. Change from baseline to the average Hb are observed values. Missing hemoglobin data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the Monte Carlo Markov Chain (MCMC) imputation model with treatment, baseline hemoglobin, randomization stratification factors and the available non missing hemoglobin for each scheduled week.


Secondary Outcome Measures :
  1. Percentage of Participants with Hb Response During Weeks 28 to 36 [ Time Frame: Weeks 28 to 36 ]
    Hb response during weeks 28-36, was defined as mean Hb from 10-12 g/dL without receiving rescue therapy in the 6 weeks prior to, or during, the evaluation period. The percentages and 95% CI were unadjusted, the exact method of Clopper-Pearson was used for 95% CI. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to end of treatment (EOT) Visit or last non-missing Hb assessment (for participants who died during the treatment period).

  2. Change From BL in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28 [ Time Frame: Baseline and weeks 12 to 28 ]
    Baseline LDL was defined as the LDL value on Day 1. If this value was missing, the latest value prior to first study drug administration was used.

  3. Mean Monthly Intravenous (IV) Iron Use [ Time Frame: Day 1 to week 36 ]
    Participants with no or missing medication records of IV Iron have their monthly IV Iron use set to 0 mg. For participants who took IV Iron, but without a dosing frequency, the average values were set to missing.

  4. Change From BL in Short Form-36 (SF-36) Health Survey Physical Functioning (PF) Sub-score to the Average of Weeks 12 to 28 [ Time Frame: Baseline and weeks 12 to 28 ]
    Baseline SF-36 PF was defined as the SF-36 PF value on Day 1.The SF-36 is a Quality of Life (QoL) instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 contains 36 items that measure eight scales: (1) physical functioning (PF); (2) role limitations due to physical health problems (RP); (3) bodily pain (BP); (4) social functioning (SF); (5) general health perceptions (GH); (6) role limitations due to emotional problems (RE); (7) vitality, energy or fatigue (VT); and (8) mental health(MH). Each scale is transformed into 0-100 score, with higher scores indicating better health status. The SF-36 PF consists of 11 questions focused on health and ability to do usual activities, with higher scores indicating better health status.

  5. Change From BL in SF-36 Vitality (VT) Sub-score to the Average of Weeks 12 to 28 [ Time Frame: Baseline and weeks 12 to 28 ]
    Baseline VT Subscore was defined as the VT value on Day 1. The SF-36 is a QoL instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 vitality has four questions with score range from 0-100 with higher scores indicating better vitality status.

  6. Change From BL in Mean Arterial Pressure (MAP) to the Average of Weeks 20 to 28 [ Time Frame: Baseline and weeks 20 to 28 ]
    Baseline MAP was defined as the MAP value on Day 1. If this value was missing, the latest value prior to first study drug administration was used. Mean Arterial Pressure (MAP) is derived as: MAP = (2/3)*DBP + (1/3)*SBP.

  7. Time to First Occurrence of an Increase in Blood Pressure [ Time Frame: Weeks 1 to 36 ]
    Increase in Blood Pressure was defined as either: Systolic Blood Pressure (SBP) ≥ 170 mmHg and an increase from BL ≥ 20 mmHg, or as: Diastolic Blood Pressure (DBP) ≥ 100 mmHg and an increase from BL ≥ 15 mmHg. For participants who have experienced more than one event, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.

  8. Change From BL in Mean Arterial Pressure (MAP) to the Average MAP Value of Weeks 20 to 28 [ Time Frame: Weeks 20 to 28 ]
    Baseline MAP was defined as the MAP value on day 1. If this value was missing, the latest value prior to first study drug administration was used. Mean Arterial Pressure (MAP) is derived as: MAP = (2/3)*DBP + (1/3)*SBP.

  9. Time to First Occurrence of an Increase in Blood Pressure [ Time Frame: Weeks 1 to 36 ]
    Increase in Blood Pressure was defined as either: SBP ≥ 170 mmHg and an increase from BL ≥ 20 mmHg, or as: DBP ≥ 100 mmHg and an increase from BL ≥ 15 mmHg. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.

  10. Percentage of Participants with a Hb Response During Weeks 28 and 36 Regardless of Use of Rescue Therapy [ Time Frame: Weeks 28 to 36 ]
    Hb response was defined as mean Hb during weeks 28 to 36 within the target range of 10.0 to 12.0 g/dL. The percentages and 95% CI are unadjusted, the exact method of Clopper-Pearson was used for 95% CI.

  11. Change From BL in Hb to Each Postdosing Time Point [ Time Frame: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18,20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72,76, 80, 84, 88, 92, 96, 100, and 104 ]
    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).

  12. Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy [ Time Frame: Weeks 28 to 36, 44 to 52, and 96 to 104 ]
    Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose). Averaged Hb values over weeks 28-36, weeks 44-52 and weeks 96-104 are observed values.

  13. Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy [ Time Frame: Baseline and weeks 28 to 36, 44 to 52, and 96 to 104 ]
    Change from baseline to the average Hb are observed values. Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose).

  14. Percentage of Hb Values ≥ 10 g/dL and Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy [ Time Frame: Weeks 28-36, 44-52 and 96-104 ]
    Percentage for each participant was calculated from the Number of Hb values within 10.0-12.0 g/dL / Total number of Hb values*100 in weeks 28 to 36, 44 to 52 and 96 to 104 without use of rescue therapy within 6 weeks prior to and during the 8 week evaluation period.

  15. Number of Hospitalizations [ Time Frame: Baseline to End of Treatment (EOT) (Up to week 104) ]
    The number of hospitalizations per participant were calculated during the Efficacy Emergent Period. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). It included all Non-Hemodialysis (HD) hospitalizations. The HD days were not counted as hospitalizations, even when performed overnight.

  16. Number of Days of Hospitalization per Year [ Time Frame: Baseline to EOT (Up to week 104) ]
    The number of days of hospitalizations per year was calculated as the sum of the durations of all non-HD hospitalizations in days (Date of discharge - Date of admission + 1)] / (duration of efficacy emergent period in days / 365.25). In case of missing dates, the hospitalization duration was imputed by the average duration per stay derived from the participants with non-missing duration within the same treatment group.

  17. Time to First Hospitalization [ Time Frame: Baseline to EOT (Up to week 104) ]
    Time to first hospitalization in years was defined in years as: (First event date during the Efficacy Emergent Period - Analysis date of First dose intake +1)/365.25, and the 'First event date' was defined as 'Date of first Admission and 'Analysis Date of first dose intake. For participants without hospitalization, the time to censoring was calculated as: (Date of End of Efficacy Emergent Period - Analysis Date of first dose intake + 1) / 365.25. Date of End of Efficacy Emergent Period was defined as as the treatment period up to the EOT visit. For participants who have experienced more than one hospitalization, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.

  18. Time to First Use of Rescue Therapy [ Time Frame: Baseline to EOT (Up to week 104) ]
    Rescue therapy was defined as red blood cell (RBC) transfusion for both treatment groups and ESA for roxadustat participants. Only rescue medication that was started during the study treatment and up to end of efficacy emergent period was taken into account and considered as use of rescue medication. For participants who have experienced more than one use of rescue therapy, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.

  19. Time to First RBC Transfusion [ Time Frame: Baseline to EOT (Up to week 104) ]
    For participants who have experienced more than one RBC transfusion, only their first event following study treatment was used. For RBC transfusions, when the number of units was not given but the volume transfused was, the number of units were estimated by volume transfused/250 mL (for transfusion of packed cell units) or volume transfused/500 mL (for transfusion of full blood). Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.

  20. Mean Monthly Number of RBC Packs Per Participant [ Time Frame: Baseline to EOT (Up to week 104) ]
    During efficacy emergent period, the mean monthly number of RBC packs was calculated as the sum of blood volume and units transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. Participants without medication records of RBC have their number of RBC packs and volume set to 0.

  21. Mean Monthly Volume of RBC Transfusion Per Participant [ Time Frame: Baseline to EOT (Up to week 104) ]
    During Efficacy Emergent Period, the mean monthly volume of blood transfused was calculated as the sum of blood volume and units transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period).

  22. Time to First Use of IV Iron Supplementation [ Time Frame: Baseline to EOT (Up to week 104) ]
    For participants who have received more than one IV iron, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.

  23. Mean Monthly Intravenous (IV) Iron per Participant During Weeks 37-52 and Weeks 53-104 [ Time Frame: Weeks 37-52 and weeks 53-104 ]
    Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg.

  24. Percentage of Participants with Oral Iron Use Only [ Time Frame: Baseline to EOT (Up to week 104) ]
    Percentage of participants with/without IV iron only was calculated based on total number of participants within the Efficacy Emergent Period. The Efficacy Emergent Period is defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period).

  25. Change From BL to Each Post-dosing Study Visit in Total Cholesterol [ Time Frame: Baseline and weeks 8, 28, 52, 104 ]
    Baseline assessment was the assessment from Day 1 visit. If baseline value was missing, then the latest screening period value was used as the baseline regardless of fasting status.

  26. Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein cholesterol (HDL-C) Ratio [ Time Frame: Baseline and weeks 8, 28, 52, 104 ]
    Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.

  27. Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol [ Time Frame: Baseline and weeks 8, 28, 52, 104 ]
    Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.

  28. Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) [ Time Frame: Baseline and weeks 8, 28, 52, 104 ]
    Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.

  29. Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) [ Time Frame: Baseline and weeks 8, 28, 52, 104 ]
    Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.

  30. Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio [ Time Frame: Baseline and weeks 8, 28, 52, 104 ]
    Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used.

  31. Number of Participants with Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 [ Time Frame: Weeks 12 to 28 ]
    Missing category for Fasting Only includes non-fasting participants and the participants with missing values.

  32. Number of Participants with CKD Who Achieved Antihypertensive Treatment Goal [ Time Frame: Weeks 12 to 28 ]
    Achieved antihypertensive treatment goal was defined as SBP < 140 mmHg and DBP < 90 mmHg over an evaluation period based on the average of available values in weeks 12-28 (pre-dialysis).

  33. Change From BL to the Average of Weeks 12 to 28 in SF-36 Physical Component Score [ Time Frame: Baseline and weeks 12 to 28 ]
    Baseline SF-36 PCS was defined as the SF-36 PCS value on Day 1. The SF-36 is a QoL instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 contains 36 items that measures eight scales: (1) physical functioning (PF); (2) role limitations due to physical health problems (RP); (3) bodily pain (BP); (4) social functioning (SF); (5) general health perceptions (GH); (6) role limitations due to emotional problems (RE); (7) vitality, energy or fatigue (VT); and (8) mental health (MH). The physical component summary was calculated based on all 8 scales of health. Each scale is transformed into 0-100 score, with higher scores indicating better health status.

  34. Change From BL to the Average of Weeks 12 to 28 in Anemia Subscale (AnS) ("Additional Concerns") of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score [ Time Frame: Baseline and weeks 12 to 28 ]
    Baseline FACT-An AnS was defined as the FACT-An Ans value on Day 1. The Functional Assessment of Cancer Therapy - General (FACT-G; version 4) 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 'additional concerns' section contains 20 items: 13 fatigue specific items plus 7 additional items related to anemia. The 13 fatigue items plus the seven additional items related to anemia comprise the Anemia Subscale (AnS). Each individual item is scored from 0 (Not at all) to 4 (Very much), and then the total score is obtained by summation of the scores, with final higher score indicating better QoL.

  35. Change From BL to the Average Value of Weeks 12 to 28 in Total FACT-An Score [ Time Frame: Baseline and weeks 12 to 28 ]
    Baseline Total FACT-An Score was defined as the FACT-An Total Score value on Day 1. Administration of the FACT-G plus the Anemia Subscale (AnS) is referred to as the FACT-An. The Functional Assessment of Cancer Therapy- General (FACT-G) Version 4 contains 27 items that cover 4 dimensions of physical well-being (PWB)—7 items, functional (FWB)—7 items, social/family (SWB)—7 items each, and emotional (EWB)—6 items. Each individual item is scored from 0 (Not at all) to 4 (Very much), and then the total score is obtained by summation of the scores, with final higher score indicating better QoL.

  36. Change From BL to the Average of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score [ Time Frame: Baseline and weeks 12 to 28 ]
    Baseline assessment was defined as the value on Day 1. The EuroQol Questionnaire -5 Dimensions -5 Levels (EQ-5D-5L) is a self-reported questionnaire, used as a measure of respondents' Health Related Quality of Life (HRQoL) and utility values. The EQ-5D consists of the descriptive system and the visual analogue scale (VAS). The EQ-5D descriptive system comprises 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, extreme problems. The VAS records the respondent's self rated health status on a graduated (0-100) scale, where the endpoints are labeled 'Best imaginable health state' and 'Worst imaginable health state' with higher scores for higher HRQoL.

  37. Percentage of Participants with Improvements Measured by Patients' Global Impression of Change (PGIC) [ Time Frame: Baseline and weeks 8, 12, 28, 36, 52, 76, 104 ]
    The PGIC is a patient-rated instrument that measures change in participant's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), when compared to the start of treatment. The percentage of participants presented includes very much improved, much improved and minimally improved.

  38. Change From BL in Serum Hepcidin [ Time Frame: Baseline and weeks 4, 12, 20, 36, 52, 104, and End of Study (EOS - up to 108 weeks) ]
    Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.

  39. Change From BL in Serum Ferritin [ Time Frame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104, and EOS (up to 108 weeks) ]
    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.

  40. Change From BL in Transferrin Saturation (TSAT) [ Time Frame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 and EOS (up to 108 weeks) ]
    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.

  41. Change From BL in Glycated Hemoglobin (HbA1c) Level [ Time Frame: Baseline and weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to 108 weeks) ]
    Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.

  42. Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to EOS (Up to week 108) ]
    Safety was assessed by evaluation of the following variables: (TEAEs; frequency, severity, seriousness, and relationship to study drug), Vital signs (systolic and diastolic blood pressure, pulse, respiratory rate and weight), Clinical laboratory variables (hematology, biochemistry including liver enzymes and total bilirubin, and urinalysis), Physical examination, 12-lead electrocardiogram (ECG) and Vascular Access Thrombosis. All AEs collected during the Safety Emergent Period were counted as TEAE. The TEAE was defined as an adverse event (AE) if it was observed after starting administration of the roxadustat or ESA. Any clinically significant abnormalities were reported as an AEs. All reported deaths after the first study drug administration and up to 28 days after the Analysis Date of Last Dose and considering last dosing frequency.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Main Inclusion:

  • Participant is on stable hemodialysis (HD), hemodiafiltration (HDF) or peritoneal dialysis (PD) treatment with the same mode of dialysis for ≥4 months prior to randomization.
  • Participant is on IV or SC epoetin or IV or SC darbepoetin alfa treatment for ≥8 weeks prior to randomization with stable weekly doses (during 4 weeks prior to randomization).
  • Mean of the participant's three most recent Hb values, as measured by central laboratory, during the Screening Period.
  • Participant's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are ≤3 x upper limit of normal (ULN), and total bilirubin (TBL) is ≤1.5 x ULN

Exclusion Criteria:

Main Exclusion:

  • Participant has received a red blood cell (RBC) transfusion within 8 weeks prior to randomization.
  • Participant has a known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than Chronic Kidney Disease (CKD).
  • Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thrombo-embolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
  • Participant has had uncontrolled hypertension, in the opinion of the investigator, within 2 weeks prior to randomization.
  • Participant has a history of malignancy, except for the following: cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps.
  • Participant has had any prior organ transplant (that has not been explanted), or participant is scheduled for organ transplantation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02278341


Locations
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Sponsors and Collaborators
Astellas Pharma Europe B.V.
FibroGen
Investigators
Layout table for investigator information
Study Director: Study Physician Astellas Pharma Europe B.V.
Additional Information:
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Responsible Party: Astellas Pharma Europe B.V.
ClinicalTrials.gov Identifier: NCT02278341    
Other Study ID Numbers: 1517-CL-0613
2013-001497-16 ( EudraCT Number )
First Posted: October 30, 2014    Key Record Dates
Last Update Posted: February 10, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL: https://www.clinicalstudydatarequest.com/
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Europe B.V. ):
ASP1517
FG-4592
Anemia
End Stage Renal Disease (ESRD)
Erythropoetin Stimulating Agents (ESAs)
Chronic Kidney Disease
Hematopoetic Agents
HIF-PH inhibitor
Hemoglobin
Dialysis
roxadustat
Additional relevant MeSH terms:
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Kidney Diseases
Kidney Failure, Chronic
Anemia
Hematologic Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Epoetin Alfa
Darbepoetin alfa
Hematinics