Anaemia, Aspergillosis, Allergic Bronchopulmonary
Conditions
Keywords
erythropoiesis stimulating agents, GSK1278863, daprodustat, anemia, chronic kidney disease, hemoglobin, recombinant human erythropoietin
Brief summary
The purpose of this multi-center event-driven study in participants with anemia associated with chronic kidney disease (CKD) to evaluate the safety and efficacy of daprodustat.
Interventions
DRUGDaprodustat
Daprodustat dose is based on prior ESA dose, the dose is adjusted thereafter in order to achieve the target range.
DRUGrhEPO
The initial ESA dose is based on converting the prior ESA dose to the nearest available study rhEPO dose and is administered IV. The dose is adjusted thereafter in order to achieve the target range.
DRUGPlacebo
Oral placebo tablets will be taken from Week -4 up to randomization (Day 1).
DRUGIron therapy
Participants will receive supplemental iron therapy if ferritin is \<=100 ng/mL or TSAT is \<=20%. The investigator will choose the route of administration and dose of iron.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18 to 99 years of age (inclusive). * Erythropoietin-stimulating agents (ESAs): Use of any approved ESA for at least the 6 weeks prior to screening and between screening and randomization. * Hgb concentration: On Week -8: Hgb 8 to 12 grams per deciliter (g/dL). On randomization (Day 1): Hgb 8 to 11 g/dL and receiving at least the minimum ESA dose. Hgb \>11 g/dL to 11.5 g/dL and receiving greater than the minimum ESA dose. * Dialysis: On dialysis \>90 days prior to screening and continuing on the same mode of dialysis from screening (Week -8) through to randomization (Day 1). * Frequency of Dialysis: Hemodialysis (HD) \>=2 times/week and peritoneal dialysis (PD) \>=5 times/week. Home hemodialysis \>=2 times/week. * Compliance with placebo \[randomization (Day 1) only\]: \>=80% and \<=120% compliance with placebo during run-in period. * Informed consent (screening only): capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Exclusion criteria
* Kidney transplant: Planned living-related or living-unrelated kidney transplant within 52 weeks after study start (Day 1). * Ferritin: \<=100 nanograms (ng)/milliliter (mL) (\<=100 micrograms/liter \[L\]) at screening. * Transferrin saturation (TSAT) (screening only): \<=20%. * Aplasias: History of bone marrow aplasia or pure red cell aplasia. * Other causes of anemia: Untreated Pernicious anemia, thalassemia major, sickle cell disease or myelodysplastic syndrome. * Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant GI bleeding \<=4 weeks prior to screening through to randomization (Day 1). * MI or acute coronary syndrome: \<=4 weeks prior to screening through to randomization (Day 1). * Stroke or transient ischemic attack: \<=4 weeks prior to screening through to randomization (Day 1). * Heart failure (HF): Chronic Class IV HF, as defined by the New York Heart Association (NYHA) functional classification system. * Current uncontrolled hypertension: Current uncontrolled hypertension as determined by the investigator that would contraindicate the use of recombinant human erythropoietin (rhEPO). * Bazett's corrected QT interval (QTcB) (Day 1): QTcB \>500 millisecond (msec), or QTcB \>530 msec in subjects with bundle branch block. There is no QT Interval Corrected for Heart Rate (QTc) exclusion for subjects with a predominantly ventricular paced rhythm. * Alanine transaminase (ALT): \>2x upper limit of normal (ULN) at screening. * Bilirubin: \>1.5xULN at screening. * Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. * Malignancy: History of malignancy within the 2 years prior to screening through to randomization (Day 1) or currently receiving treatment for cancer, or complex kidney cyst (example \[e.g.\] Bosniak Category II F, III or IV) \> 3 centimeter (cm); with the exception of localized squamous cell or basal cell carcinoma of the skin that has been definitively treated \>=4 weeks prior to screening. * Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product, or epoetin alfa or darbepoetin alfa. * Drugs and supplements: Use of strong inhibitors of Cytochrome P4502C8 (CYP2C8) (e.g., gemfibrozil) or strong inducers of CYP2C8 (e.g., rifampin/rifampicin). * Other study participation: Use of other investigational agent or device prior to screening through to randomization (Day 1). * Prior treatment with daprodustat: Any prior treatment with daprodustat for treatment duration of \>30 days. * Females only: Subject is pregnant \[as confirmed by a positive serum human chorionic gonadotrophin (hCG) test for females of reproductive potential (FRP) only\], subject is breastfeeding, or subject is of reproductive potential and does not agree to follow one of the contraceptive options listed in the List of Highly Effective Methods for Avoiding Pregnancy. * Other Conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance (e.g., intolerance to rhEPO) or prevent understanding of the aims or investigational procedures or possible consequences of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period: Non-inferiority Analysis | Up to 3.9 person-years for CV follow-up time period | Time to MACE defined as the time to first occurrence of Clinical Events Committee (CEC) adjudicated MACE (composite of all-cause mortality, non-fatal myocardial infarction \[MI\] and non-fatal stroke) was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) plus (+) 1. The incidence rate per 100 person years calculated as (100 multiplied by \[\*\] number of participants with at least 1 event) divided by \[/\] first event person-years) is presented along with 95 percent (%) confidence interval (CI). First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. |
| Mean Change From Baseline in Hemoglobin (Hgb) Levels During Evaluation Period (Week 28 to Week 52) | Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52) | Blood samples were collected from participants for hemoglobin measurements. Hemoglobin during the evaluation period was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis, missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputation methods. Change from Baseline was defined as post-Baseline value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure During CV Events Follow-up Time Period | Up to 3.9 person-years for CV follow-up time period | Time to first occurrence of adjudicated MACE or hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method. |
| Mean Average Monthly On-treatment IV Iron Dose Per Participant | Day 1 to Week 52 | Average monthly IV iron dose (milligrams) per participant from Day 1 to Week 52 was determined by calculating the total IV iron dose per participant from treatment start date + 1 to the earliest of (Week 52 visit date, first blood (red blood cell \[RBC\] or whole blood) transfusion date, and treatment stop date + 1 day) which corresponds to the time while the participant was on randomized treatment and before receiving a blood transfusion. This total IV iron dose was divided by (the number of days from treatment start date + 1 to the earliest of (Week 52 visit date, first blood transfusion date (RBC or whole blood), and treatment stop date +1) / 30.4375 days). This endpoint was adjusted for multiplicity using the Holm-Bonferonni method. |
| Time to First Occurrence of Adjudicated All-Cause Mortality During Vital Status for Follow-up Time Period | Up to 3.9 person-years for vital status follow-up time period | Time to first occurrence of adjudicated all-cause mortality was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the vital status for follow-up time period. |
| Time to First Occurrence of Adjudicated CV Mortality During CV Events Follow-up Time Period | Up to 3.9 person-years for CV follow-up time period | Time to first occurrence of adjudicated CV mortality was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. |
| Time to First Occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) During CV Events Follow-up Time Period | Up to 3.9 person-years for CV follow-up time period | Time to first occurrence of adjudicated MI (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. |
| Time to First Occurrence of Adjudicated Stroke (Fatal and Non-Fatal) During CV Events Follow-up Time Period | Up to 3.9 person-years for CV follow-up time period | Time to first occurrence of adjudicated stroke (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. |
| Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Up to 3.9 person-years for CV follow-up time period | Number of participants with adjudicated MACE or hospitalization for heart failure (recurrent events analysis) is presented, categorized by number of occurrences of adjudicated MACE or hospitalization for heart failure per participant. |
| Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI During CV Events Follow-up Time Period | Up to 3.9 person-years for CV follow-up time period | Time to first occurrence of adjudicated CV mortality or non-fatal MI was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. |
| Time to First Occurrence of All-Cause Hospitalization During CV Events Follow-up Time Period | Up to 3.9 person-years for CV follow-up time period | All-cause hospitalization events were hospital admissions recorded on the Hospitalization electronic case report form (eCRF) with a hospitalization duration \>=24 hours. Time to first occurrence of all-cause hospitalization was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. |
| Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52) | Week 28 to Week 52 | Mean Hgb during the evaluation period was defined as the mean of all evaluable Hgb values during the evaluation period (Week 28 to Week 52) including any evaluable unscheduled Hgb values that were taken during this time period. Hemoglobin responders were defined as participants with a mean Hgb during the evaluation period that falls within the Hgb analysis range of 10-11.5 g/dL. |
| Time to First Occurrence of All-Cause Hospital Re-admission Within 30 Days During CV Events Follow-up Time Period | Up to 3.9 person-years for CV follow-up time period | All-cause hospital re-admissions within 30days are defined as hospital admissions recorded on hospitalization eCRF with hospitalization duration of \>=24 hours and admission date within 30days following previous discharge date of all-cause hospitalization event, where previous hospitalization was \>=24 hours. Time to first occurrence of all-cause hospital re-admission within 30days was analyzed using Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date)+1. Incidence rate per 100person years calculated as(100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. |
| Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic Events During CV Events Follow-up Time Period | Up to 3.9 person-years for CV follow-up time period | Time to first occurrence of adjudicated MACE or hospitalization for heart failure or thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. |
| Time to First Occurrence of Adjudicated Hospitalization for Heart Failure During CV Events Follow-up Time Period | Up to 3.9 person-years for CV follow-up time period | Time to first occurrence of adjudicated hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. |
| Time to First Occurrence of Adjudicated Thromboembolic Events During CV Events Follow-up Time Period | Up to 3.9 person-years for CV follow-up time period | Time to first occurrence of adjudicated thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. |
| Change From Baseline in Post-randomization Hemoglobin Levels at Week 52 | Baseline (Pre-dose on Day 1) and Week 52 | Blood samples were collected from participants for hemoglobin measurements. Change from Baseline was defined as post-Baseline value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using mixed model repeated measures (MMRM) model fitted from Baseline up to Week 52, excluding values collected during the stabilization period, with factors for treatment, time, dialysis type, region, Baseline hemoglobin and Baseline hemoglobin by time and treatment by time interactions. |
| Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis | Week 28 to Week 52 | Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / \[Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) - Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)\]. |
| Time to First Occurrence of Adjudicated MACE During CV Events Follow-up Time Period: Superiority Analysis | Up to 3.9 person-years for CV follow-up time period | Time to MACE defined as the time to first occurrence of CEC adjudicated MACE was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariate. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method. |
| Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Non-inferiority Analysis | Week 28 to end of study (3.9 person-years for follow-up time period) | Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / \[Earlier of (Date of the last evaluable Hgb value, End of study date)- Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)\]. |
| Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Superiority Analysis | Week 28 to end of study (3.9 person-years for follow-up time period) | Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / \[Earlier of (Date of the last evaluable Hgb value, End of study date)- Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)\]. |
| Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52 | Baseline (Week -4) and Week 52 | SBP, DBP and MAP were measured in a semi-supine or seated position in the dialysis chair after at least a 5-minutes of rest. MAP is the average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using MMRM model with treatment group + time + dialysis type + region + Baseline value + Baseline value\*time + treatment group\*time, using an unstructured covariance matrix. Data for post-dialysis BP measurements have been presented. |
| Change From Baseline in SBP, DBP, MAP at End of Treatment | Baseline (Week -4) and 45.1 months | SBP, DBP and MAP were measured in a semi-supine or seated position in the dialysis chair after at least a 5-minutes of rest. MAP is an average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. This analysis was carried out by using ANCOVA model with terms for treatment group, dialysis type, region and Baseline value. Data for post-dialysis BP measurements have been presented. |
| Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years | Day 1 to end of study (3.9 person-years for follow-up time period) | BP exacerbation was defined (based on post-dialysis) as: SBP \>= 25 millimeter of mercury (mmHg) increased from Baseline or SBP \>=180 mmHg; DBP \>=15 mmHg increased from Baseline or DBP \>=110 mmHg. The BP exacerbation events per 100 participant years was estimated using the negative binomial model with treatment, dialysis type and region as covariates and the logarithm of time on-treatment as an offset variable. Data for post-dialysis BP measurements have been presented. |
| Number of Participants With at Least One BP Exacerbation Event During Study | Day 1 to end of study (3.9 person-years for follow-up time period) | BP exacerbation was defined as: SBP \>= 25 mmHg increased from Baseline or SBP \>=180 mmHg; DBP \>=15 mmHg increased from Baseline or DBP \>=110 mmHg. Number of participants with at least one BP exacerbation event is presented. |
| Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria | Day 1 to 45.1 months | Percentage of participants permanently stopping randomized treatment due to meeting rescue criteria has been presented. |
| Change From Baseline in On-Treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52 | Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52 | The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). The PCS is an average score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. PCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. |
| Change From Baseline in On-Treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52 | The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). MCS is an average score derived from 4 domains (vitality, social functioning, role-emotional and mental health) representing overall mental health. MCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. |
| Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52 | The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: bodily pain, general health, mental health, role-emotional (role limitations caused by emotional problems), role-physical (role limitations caused by physical problems), social functioning (Social fun), physical functioning (Phy. fun) and vitality. Each domain is scored from 0 (poorer health) to 100 (better health). Each domain score ranges from 0 to 100, higher score indicates a better health state and better functioning. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. |
| Change From Baseline in On-Treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52 | The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Vitality score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. |
| Change From Baseline in On-Treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52 | The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Physical functioning score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus (-) Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. |
| Change From Baseline in On-Treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52 | Baseline (Pre-dose on Day 1) and Week 52 | EQ-5D-5L is self-assessment questionnaire,consisting of 5 items covering 5 dimensions (mobility,self care,usual activities,pain/discomfort and anxiety/depression). Each dimension is measured by 5-point Likert scale (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Each of these 5 figure health states were converted to a single index score by applying country-specific value set formula that attaches weights to dimensions and levels. Range for EQ-5D-5L index score is -0.594 (worst health) to 1 (full health state). Change from Baseline was calculated as on-treatment visit value-Baseline value. Baseline was latest non-missing pre-dose assessment on or before randomization date. |
| Change From Baseline in On-Treatment EuroQol Visual Analogue Scale (EQ-VAS) at Week 52 | Baseline (Pre-dose on Day 1) and Week 52 | The EQ VAS records the respondent's self-rated health on a vertical VAS, ranging from 0 to 100, where 0 represents the worst health one can imagine and 100 represents the best health one can imagine. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. |
| Change From Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52 | Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52 | The PGI-S is a 1-item questionnaire designed to assess participant's impression of disease severity on a 5-point disease severity scale (0=absent, 1=mild, 2=moderate, 3=severe, or 4=very severe). A higher score indicated worse outcome. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. |
| Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority Analysis | Week 28 to Week 52 | Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / \[Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) - Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)\]. |
| Time to First Occurrence of Adjudicated MACE or Thromboembolic Event During CV Events Follow-up Time Period | Up to 3.9 person-years for CV follow-up time period | Time to first occurrence of adjudicated MACE or thromboembolic event (vascular access thrombosis, symptomatic deep vein thrombosis or symptomatic pulmonary embolism) was analyzed using a Cox proportional hazards regression model with with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, Denmark, Estonia, France, Germany, Greece, Hungary, India, Italy, Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
This was a randomized, open-label (sponsor blind), active-controlled, parallel-group, event-driven study conducted at 431 centers in 35 countries. Participants were randomized to receive daprodustat and recombinant human erythropoietin (rhEPO) (epoetin alfa or darbepoetin alfa).
Pre-assignment details
A total of 2964 participants were randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Daprodustat Participants received placebo tablets orally once daily in run-in period from Week -4 up to randomization (Day 1) and subsequently received daprodustat tablets at dose levels of 1, 2, 4, 6, 8, 10, 12, 16 and 24 milligrams (mg) orally once daily until the required number of major adverse cardiovascular event (MACE) occurred, at approximately 45.1 months of randomized treatment. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (10 to 11 grams per deciliter \[g/dL\]). | 1,487 |
| rhEPO Participants received placebo tablets orally once daily in run-in period from Week -4 up to randomization (Day 1) and subsequently received treatment with rhEPO. Participants on hemodialysis received epoetin alfa as intravenous (IV) injection once weekly or three-times weekly with total weekly dose levels ranging from 1500 to 60,000 Units. Participants on peritoneal dialysis received subcutaneous (SC) injection of darbepoetin alfa every 1, 2, or 4 weeks with 4-weekly total dose levels ranging from 20 to 400 microgram (mcg). Darbepoetin could be given by IV injection for peritoneal dialysis participants switching to hemodialysis. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (10 to 11 g/dL) and administered until the required number of MACE events occurred, at approximately 45.1 months of randomized treatment. | 1,477 |
| Total | 2,964 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Investigator Site Closed | 55 | 57 |
| Overall Study | Lost to Follow-up | 17 | 12 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrawal by Subject | 44 | 42 |
Baseline characteristics
| Characteristic | Daprodustat | Total | rhEPO |
|---|---|---|---|
| Age, Continuous | 57.2 Years STANDARD_DEVIATION 14.29 | 57.2 Years STANDARD_DEVIATION 14.47 | 57.3 Years STANDARD_DEVIATION 14.65 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 19 Participants | 51 Participants | 32 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 36 Participants | 82 Participants | 46 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 97 Participants | 183 Participants | 86 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 3 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 40 Participants | 85 Participants | 45 Participants |
| Race/Ethnicity, Customized Black or African American | 228 Participants | 461 Participants | 233 Participants |
| Race/Ethnicity, Customized Mixed Asian Race | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Mixed Race | 43 Participants | 67 Participants | 24 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 26 Participants | 51 Participants | 25 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 8 Participants | 22 Participants | 14 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 987 Participants | 1955 Participants | 968 Participants |
| Sex: Female, Male Female | 636 Participants | 1266 Participants | 630 Participants |
| Sex: Female, Male Male | 851 Participants | 1698 Participants | 847 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 294 / 1,487 | 300 / 1,477 |
| other Total, other adverse events | 830 / 1,482 | 827 / 1,474 |
| serious Total, serious adverse events | 773 / 1,482 | 748 / 1,474 |
Outcome results
Primary
Mean Change From Baseline in Hemoglobin (Hgb) Levels During Evaluation Period (Week 28 to Week 52)
Blood samples were collected from participants for hemoglobin measurements. Hemoglobin during the evaluation period was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis, missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputation methods. Change from Baseline was defined as post-Baseline value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Time frame: Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Daprodustat | Mean Change From Baseline in Hemoglobin (Hgb) Levels During Evaluation Period (Week 28 to Week 52) | 0.28 Grams per deciliter | Standard Error 0.022 |
| rhEPO | Mean Change From Baseline in Hemoglobin (Hgb) Levels During Evaluation Period (Week 28 to Week 52) | 0.10 Grams per deciliter | Standard Error 0.022 |
95% CI: [0.12, 0.24]
Primary
Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period: Non-inferiority Analysis
Time to MACE defined as the time to first occurrence of Clinical Events Committee (CEC) adjudicated MACE (composite of all-cause mortality, non-fatal myocardial infarction \[MI\] and non-fatal stroke) was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) plus (+) 1. The incidence rate per 100 person years calculated as (100 multiplied by \[\*\] number of participants with at least 1 event) divided by \[/\] first event person-years) is presented along with 95 percent (%) confidence interval (CI). First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (Intent-to-treat \[ITT\]) Population comprised of all randomized participants. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period: Non-inferiority Analysis | 11.07 Events per 100 person years |
| rhEPO | Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period: Non-inferiority Analysis | 11.86 Events per 100 person years |
95% CI: [0.81, 1.07]
Secondary
Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years
BP exacerbation was defined (based on post-dialysis) as: SBP \>= 25 millimeter of mercury (mmHg) increased from Baseline or SBP \>=180 mmHg; DBP \>=15 mmHg increased from Baseline or DBP \>=110 mmHg. The BP exacerbation events per 100 participant years was estimated using the negative binomial model with treatment, dialysis type and region as covariates and the logarithm of time on-treatment as an offset variable. Data for post-dialysis BP measurements have been presented.
Time frame: Day 1 to end of study (3.9 person-years for follow-up time period)
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years | 207.13 Events per 100 participant years |
| rhEPO | Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years | 206.38 Events per 100 participant years |
p-value: 0.52995% CI: [0.91, 1.11]Negative binomial model
Secondary
Change From Baseline in On-Treatment EuroQol Visual Analogue Scale (EQ-VAS) at Week 52
The EQ VAS records the respondent's self-rated health on a vertical VAS, ranging from 0 to 100, where 0 represents the worst health one can imagine and 100 represents the best health one can imagine. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Time frame: Baseline (Pre-dose on Day 1) and Week 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Daprodustat | Change From Baseline in On-Treatment EuroQol Visual Analogue Scale (EQ-VAS) at Week 52 | -1.0 Scores on a scale | Standard Error 0.86 |
| rhEPO | Change From Baseline in On-Treatment EuroQol Visual Analogue Scale (EQ-VAS) at Week 52 | 0.8 Scores on a scale | Standard Error 0.87 |
p-value: 0.929295% CI: [-4.2, 0.6]MMRM
Secondary
Change From Baseline in On-Treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52
EQ-5D-5L is self-assessment questionnaire,consisting of 5 items covering 5 dimensions (mobility,self care,usual activities,pain/discomfort and anxiety/depression). Each dimension is measured by 5-point Likert scale (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Each of these 5 figure health states were converted to a single index score by applying country-specific value set formula that attaches weights to dimensions and levels. Range for EQ-5D-5L index score is -0.594 (worst health) to 1 (full health state). Change from Baseline was calculated as on-treatment visit value-Baseline value. Baseline was latest non-missing pre-dose assessment on or before randomization date.
Time frame: Baseline (Pre-dose on Day 1) and Week 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Daprodustat | Change From Baseline in On-Treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52 | -0.0198 Scores on a scale | Standard Error 0.01179 |
| rhEPO | Change From Baseline in On-Treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52 | -0.0201 Scores on a scale | Standard Error 0.01187 |
p-value: 0.493995% CI: [-0.0326, 0.0331]MMRM
Secondary
Change From Baseline in On-Treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). MCS is an average score derived from 4 domains (vitality, social functioning, role-emotional and mental health) representing overall mental health. MCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Time frame: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Change From Baseline in On-Treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 8, n=982,936 | -0.38 Scores on a scale | Standard Error 0.254 |
| Daprodustat | Change From Baseline in On-Treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 12, n=990,943 | -0.55 Scores on a scale | Standard Error 0.262 |
| Daprodustat | Change From Baseline in On-Treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 28, n=836,819 | -1.25 Scores on a scale | Standard Error 0.286 |
| Daprodustat | Change From Baseline in On-Treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 52, n=729,707 | -1.63 Scores on a scale | Standard Error 0.311 |
| rhEPO | Change From Baseline in On-Treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 52, n=729,707 | -1.03 Scores on a scale | Standard Error 0.316 |
| rhEPO | Change From Baseline in On-Treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 8, n=982,936 | -0.21 Scores on a scale | Standard Error 0.26 |
| rhEPO | Change From Baseline in On-Treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 28, n=836,819 | -1.23 Scores on a scale | Standard Error 0.29 |
| rhEPO | Change From Baseline in On-Treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 12, n=990,943 | -0.72 Scores on a scale | Standard Error 0.268 |
p-value: 0.680795% CI: [-0.88, 0.54]MMRM
p-value: 0.325695% CI: [-0.57, 0.91]MMRM
p-value: 0.514495% CI: [-0.81, 0.78]MMRM
p-value: 0.91295% CI: [-1.47, 0.27]MMRM
Secondary
Change From Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52
The PGI-S is a 1-item questionnaire designed to assess participant's impression of disease severity on a 5-point disease severity scale (0=absent, 1=mild, 2=moderate, 3=severe, or 4=very severe). A higher score indicated worse outcome. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Time frame: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Change From Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52 | Week 8, n=1102,1064 | -0.03 Scores on a scale | Standard Error 0.024 |
| Daprodustat | Change From Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52 | Week 12, n=1102,1073 | 0.02 Scores on a scale | Standard Error 0.025 |
| Daprodustat | Change From Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52 | Week 28, n=934,933 | 0.04 Scores on a scale | Standard Error 0.027 |
| Daprodustat | Change From Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52 | Week 52, n=826,814 | 0.06 Scores on a scale | Standard Error 0.029 |
| rhEPO | Change From Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52 | Week 52, n=826,814 | 0.11 Scores on a scale | Standard Error 0.03 |
| rhEPO | Change From Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52 | Week 8, n=1102,1064 | 0.02 Scores on a scale | Standard Error 0.025 |
| rhEPO | Change From Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52 | Week 28, n=934,933 | 0.08 Scores on a scale | Standard Error 0.027 |
| rhEPO | Change From Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52 | Week 12, n=1102,1073 | 0.06 Scores on a scale | Standard Error 0.025 |
p-value: 0.042895% CI: [-0.13, 0.01]MMRM
p-value: 0.115595% CI: [-0.11, 0.03]MMRM
p-value: 0.142695% CI: [-0.12, 0.03]MMRM
p-value: 0.115295% CI: [-0.13, 0.03]MMRM
Secondary
Change From Baseline in On-Treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52
The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). The PCS is an average score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. PCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Time frame: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Change From Baseline in On-Treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52 | Week 52, n=729,707 | -0.52 Scores on a scale | Standard Error 0.248 |
| Daprodustat | Change From Baseline in On-Treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52 | Week 12, n=990,943 | 0.33 Scores on a scale | Standard Error 0.203 |
| Daprodustat | Change From Baseline in On-Treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52 | Week 8, n=982,936 | 0.30 Scores on a scale | Standard Error 0.205 |
| Daprodustat | Change From Baseline in On-Treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52 | Week 28, n=836,819 | -0.23 Scores on a scale | Standard Error 0.229 |
| rhEPO | Change From Baseline in On-Treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52 | Week 8, n=982,936 | 0.01 Scores on a scale | Standard Error 0.21 |
| rhEPO | Change From Baseline in On-Treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52 | Week 52, n=729,707 | -1.05 Scores on a scale | Standard Error 0.252 |
| rhEPO | Change From Baseline in On-Treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52 | Week 28, n=836,819 | -0.57 Scores on a scale | Standard Error 0.232 |
| rhEPO | Change From Baseline in On-Treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52 | Week 12, n=990,943 | -0.27 Scores on a scale | Standard Error 0.207 |
p-value: 0.16295% CI: [-0.29, 0.86]MMRM
p-value: 0.01895% CI: [0.04, 1.18]MMRM
p-value: 0.15395% CI: [-0.31, 0.97]MMRM
p-value: 0.068695% CI: [-0.17, 1.22]MMRM
Secondary
Change From Baseline in On-Treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Physical functioning score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus (-) Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Time frame: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Change From Baseline in On-Treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 8, n=982,936 | 0.48 Scores on a scale | Standard Error 0.237 |
| Daprodustat | Change From Baseline in On-Treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 12, n=990,943 | 0.11 Scores on a scale | Standard Error 0.24 |
| Daprodustat | Change From Baseline in On-Treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 28, n=836,819 | -0.20 Scores on a scale | Standard Error 0.273 |
| Daprodustat | Change From Baseline in On-Treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 52, n=729,707 | -0.61 Scores on a scale | Standard Error 0.291 |
| rhEPO | Change From Baseline in On-Treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 52, n=729,707 | -1.19 Scores on a scale | Standard Error 0.296 |
| rhEPO | Change From Baseline in On-Treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 8, n=982,936 | -0.16 Scores on a scale | Standard Error 0.243 |
| rhEPO | Change From Baseline in On-Treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 28, n=836,819 | -0.97 Scores on a scale | Standard Error 0.277 |
| rhEPO | Change From Baseline in On-Treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 12, n=990,943 | -0.45 Scores on a scale | Standard Error 0.246 |
p-value: 0.02995% CI: [-0.02, 1.31]MMRM
p-value: 0.050995% CI: [-0.11, 1.24]MMRM
p-value: 0.023795% CI: [0.01, 1.53]MMRM
p-value: 0.082895% CI: [-0.24, 1.39]MMRM
Secondary
Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52
The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: bodily pain, general health, mental health, role-emotional (role limitations caused by emotional problems), role-physical (role limitations caused by physical problems), social functioning (Social fun), physical functioning (Phy. fun) and vitality. Each domain is scored from 0 (poorer health) to 100 (better health). Each domain score ranges from 0 to 100, higher score indicates a better health state and better functioning. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Time frame: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | General health: Week 28, n=836,819 | -1.32 Scores on a scale | Standard Error 0.232 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Bodily pain: Week 12, n=990,943 | 0.20 Scores on a scale | Standard Error 0.267 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Bodily pain: Week 28, n=836,819 | -0.70 Scores on a scale | Standard Error 0.297 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Bodily pain: Week 52, n=729,707 | -1.12 Scores on a scale | Standard Error 0.313 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | General health: Week 8, n=982,936 | -0.39 Scores on a scale | Standard Error 0.208 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | General health: Week 12, n=990,943 | -0.59 Scores on a scale | Standard Error 0.21 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Bodily pain: Week 8, n=982,936 | -0.13 Scores on a scale | Standard Error 0.265 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | General health: Week 52, n=729,707 | -1.51 Scores on a scale | Standard Error 0.251 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Mental health: Week 8, n=982,936 | -0.43 Scores on a scale | Standard Error 0.238 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Mental health: Week 12, n=990,943 | -0.86 Scores on a scale | Standard Error 0.247 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Mental health: Week 28, n=836,819 | -1.30 Scores on a scale | Standard Error 0.267 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Mental health: Week 52, n=729,707 | -1.97 Scores on a scale | Standard Error 0.296 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-emotional: Week 8, n=982,936 | -0.10 Scores on a scale | Standard Error 0.31 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-emotional: Week 12, n=990,943 | -0.17 Scores on a scale | Standard Error 0.311 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-emotional: Week 28, n=836,819 | -0.95 Scores on a scale | Standard Error 0.335 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-emotional: Week 52, n=729,707 | -0.83 Scores on a scale | Standard Error 0.358 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-physical: Week 8, n=982,936 | 0.40 Scores on a scale | Standard Error 0.241 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-physical: Week 12, n=990,943 | 0.48 Scores on a scale | Standard Error 0.239 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-physical: Week 28, n=836,819 | -0.10 Scores on a scale | Standard Error 0.257 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-physical: Week 52, n=729,707 | -0.21 Scores on a scale | Standard Error 0.285 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Social functioning: Week 8, n=982,936 | 0.24 Scores on a scale | Standard Error 0.241 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Social functioning: Week 12, n=990,943 | 0.25 Scores on a scale | Standard Error 0.255 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Social functioning: Week 28, n=836,819 | -0.61 Scores on a scale | Standard Error 0.28 |
| Daprodustat | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Social functioning: Week 52, n=729,707 | -1.12 Scores on a scale | Standard Error 0.315 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Social functioning: Week 28, n=836,819 | -0.94 Scores on a scale | Standard Error 0.283 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Bodily pain: Week 8, n=982,936 | 0.12 Scores on a scale | Standard Error 0.272 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-emotional: Week 8, n=982,936 | -0.02 Scores on a scale | Standard Error 0.317 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Bodily pain: Week 12, n=990,943 | -0.39 Scores on a scale | Standard Error 0.274 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-physical: Week 28, n=836,819 | -0.39 Scores on a scale | Standard Error 0.26 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Bodily pain: Week 28, n=836,819 | -0.74 Scores on a scale | Standard Error 0.301 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-emotional: Week 12, n=990,943 | -0.53 Scores on a scale | Standard Error 0.318 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Bodily pain: Week 52, n=729,707 | -1.39 Scores on a scale | Standard Error 0.318 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Social functioning: Week 12, n=990,943 | -0.44 Scores on a scale | Standard Error 0.261 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | General health: Week 8, n=982,936 | -0.65 Scores on a scale | Standard Error 0.213 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-emotional: Week 28, n=836,819 | -0.90 Scores on a scale | Standard Error 0.339 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | General health: Week 12, n=990,943 | -1.04 Scores on a scale | Standard Error 0.215 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-physical: Week 52, n=729,707 | -0.60 Scores on a scale | Standard Error 0.289 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | General health: Week 28, n=836,819 | -0.99 Scores on a scale | Standard Error 0.235 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-emotional: Week 52, n=729,707 | -0.92 Scores on a scale | Standard Error 0.363 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | General health: Week 52, n=729,707 | -1.22 Scores on a scale | Standard Error 0.255 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Social functioning: Week 52, n=729,707 | -1.14 Scores on a scale | Standard Error 0.32 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Mental health: Week 8, n=982,936 | -0.47 Scores on a scale | Standard Error 0.244 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-physical: Week 8, n=982,936 | 0.32 Scores on a scale | Standard Error 0.246 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Mental health: Week 12, n=990,943 | -0.81 Scores on a scale | Standard Error 0.253 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Social functioning: Week 8, n=982,936 | 0.38 Scores on a scale | Standard Error 0.247 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Mental health: Week 28, n=836,819 | -1.43 Scores on a scale | Standard Error 0.27 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Role-physical: Week 12, n=990,943 | 0.08 Scores on a scale | Standard Error 0.245 |
| rhEPO | Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52 | Mental health: Week 52, n=729,707 | -1.16 Scores on a scale | Standard Error 0.301 |
p-value: 0.743295% CI: [-0.99, 0.5]MMRM
p-value: 0.063195% CI: [-0.16, 1.33]MMRM
p-value: 0.460495% CI: [-0.79, 0.87]MMRM
p-value: 0.268895% CI: [-0.6, 1.15]MMRM
p-value: 0.191895% CI: [-0.32, 0.84]MMRM
p-value: 0.067795% CI: [-0.14, 1.04]MMRM
p-value: 0.838695% CI: [-0.98, 0.32]MMRM
p-value: 0.792895% CI: [-0.99, 0.41]MMRM
p-value: 0.453795% CI: [-0.63, 0.71]MMRM
p-value: 0.554895% CI: [-0.74, 0.65]MMRM
p-value: 0.362695% CI: [-0.61, 0.88]MMRM
p-value: 0.972195% CI: [-1.64, 0.02]MMRM
p-value: 0.578995% CI: [-0.96, 0.78]MMRM
p-value: 0.205495% CI: [-0.51, 1.24]MMRM
p-value: 0.538995% CI: [-0.98, 0.89]MMRM
p-value: 0.428995% CI: [-0.91, 1.09]MMRM
p-value: 0.409695% CI: [-0.6, 0.75]MMRM
p-value: 0.119695% CI: [-0.27, 1.07]MMRM
p-value: 0.209395% CI: [-0.42, 1.01]MMRM
p-value: 0.167495% CI: [-0.4, 1.19]MMRM
p-value: 0.658595% CI: [-0.82, 0.54]MMRM
p-value: 0.029395% CI: [-0.03, 1.4]MMRM
p-value: 0.205795% CI: [-0.45, 1.11]MMRM
p-value: 0.484995% CI: [-0.86, 0.9]MMRM
Secondary
Change From Baseline in On-Treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Vitality score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.
Time frame: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Change From Baseline in On-Treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 8, n=982,936 | -0.23 Scores on a scale | Standard Error 0.219 |
| Daprodustat | Change From Baseline in On-Treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 28, n=836,819 | -0.79 Scores on a scale | Standard Error 0.242 |
| Daprodustat | Change From Baseline in On-Treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 12, n=990,943 | -0.17 Scores on a scale | Standard Error 0.227 |
| Daprodustat | Change From Baseline in On-Treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 52, n=729,707 | -1.19 Scores on a scale | Standard Error 0.268 |
| rhEPO | Change From Baseline in On-Treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 52, n=729,707 | -1.04 Scores on a scale | Standard Error 0.272 |
| rhEPO | Change From Baseline in On-Treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 8, n=982,936 | -0.26 Scores on a scale | Standard Error 0.224 |
| rhEPO | Change From Baseline in On-Treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 12, n=990,943 | -0.51 Scores on a scale | Standard Error 0.232 |
| rhEPO | Change From Baseline in On-Treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52 | Week 28, n=836,819 | -1.03 Scores on a scale | Standard Error 0.245 |
p-value: 0.462195% CI: [-0.58, 0.64]MMRM
p-value: 0.143995% CI: [-0.29, 0.98]MMRM
p-value: 0.239295% CI: [-0.43, 0.92]MMRM
p-value: 0.654595% CI: [-0.9, 0.6]MMRM
Secondary
Change From Baseline in Post-randomization Hemoglobin Levels at Week 52
Blood samples were collected from participants for hemoglobin measurements. Change from Baseline was defined as post-Baseline value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using mixed model repeated measures (MMRM) model fitted from Baseline up to Week 52, excluding values collected during the stabilization period, with factors for treatment, time, dialysis type, region, Baseline hemoglobin and Baseline hemoglobin by time and treatment by time interactions.
Time frame: Baseline (Pre-dose on Day 1) and Week 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Daprodustat | Change From Baseline in Post-randomization Hemoglobin Levels at Week 52 | 0.26 Grams per deciliter | Standard Error 0.032 |
| rhEPO | Change From Baseline in Post-randomization Hemoglobin Levels at Week 52 | 0.14 Grams per deciliter | Standard Error 0.032 |
95% CI: [0.03, 0.21]
Secondary
Change From Baseline in SBP, DBP, MAP at End of Treatment
SBP, DBP and MAP were measured in a semi-supine or seated position in the dialysis chair after at least a 5-minutes of rest. MAP is an average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. This analysis was carried out by using ANCOVA model with terms for treatment group, dialysis type, region and Baseline value. Data for post-dialysis BP measurements have been presented.
Time frame: Baseline (Week -4) and 45.1 months
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Change From Baseline in SBP, DBP, MAP at End of Treatment | SBP | -0.43 Millimeter of mercury | Standard Error 0.554 |
| Daprodustat | Change From Baseline in SBP, DBP, MAP at End of Treatment | DBP | -0.92 Millimeter of mercury | Standard Error 0.31 |
| Daprodustat | Change From Baseline in SBP, DBP, MAP at End of Treatment | MAP | -0.75 Millimeter of mercury | Standard Error 0.35 |
| rhEPO | Change From Baseline in SBP, DBP, MAP at End of Treatment | SBP | -0.43 Millimeter of mercury | Standard Error 0.557 |
| rhEPO | Change From Baseline in SBP, DBP, MAP at End of Treatment | DBP | -1.37 Millimeter of mercury | Standard Error 0.312 |
| rhEPO | Change From Baseline in SBP, DBP, MAP at End of Treatment | MAP | -1.06 Millimeter of mercury | Standard Error 0.351 |
p-value: 0.501295% CI: [-1.54, 1.54]ANCOVA
p-value: 0.845195% CI: [-0.42, 1.31]ANCOVA
p-value: 0.731295% CI: [-0.67, 1.28]ANCOVA
Secondary
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52
SBP, DBP and MAP were measured in a semi-supine or seated position in the dialysis chair after at least a 5-minutes of rest. MAP is the average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using MMRM model with treatment group + time + dialysis type + region + Baseline value + Baseline value\*time + treatment group\*time, using an unstructured covariance matrix. Data for post-dialysis BP measurements have been presented.
Time frame: Baseline (Week -4) and Week 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52 | SBP | -0.61 Millimeter of mercury | Standard Error 0.582 |
| Daprodustat | Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52 | DBP | -1.04 Millimeter of mercury | Standard Error 0.326 |
| Daprodustat | Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52 | MAP | -0.89 Millimeter of mercury | Standard Error 0.37 |
| rhEPO | Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52 | SBP | -0.93 Millimeter of mercury | Standard Error 0.578 |
| rhEPO | Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52 | DBP | -0.58 Millimeter of mercury | Standard Error 0.324 |
| rhEPO | Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52 | MAP | -0.71 Millimeter of mercury | Standard Error 0.368 |
p-value: 0.655195% CI: [-1.28, 1.94]MMRM
p-value: 0.158695% CI: [-1.36, 0.44]MMRM
p-value: 0.364695% CI: [-1.2, 0.84]MMRM
Secondary
Mean Average Monthly On-treatment IV Iron Dose Per Participant
Average monthly IV iron dose (milligrams) per participant from Day 1 to Week 52 was determined by calculating the total IV iron dose per participant from treatment start date + 1 to the earliest of (Week 52 visit date, first blood (red blood cell \[RBC\] or whole blood) transfusion date, and treatment stop date + 1 day) which corresponds to the time while the participant was on randomized treatment and before receiving a blood transfusion. This total IV iron dose was divided by (the number of days from treatment start date + 1 to the earliest of (Week 52 visit date, first blood transfusion date (RBC or whole blood), and treatment stop date +1) / 30.4375 days). This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.
Time frame: Day 1 to Week 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Daprodustat | Mean Average Monthly On-treatment IV Iron Dose Per Participant | 90.8 Milligrams | Standard Error 3.34 |
| rhEPO | Mean Average Monthly On-treatment IV Iron Dose Per Participant | 99.9 Milligrams | Standard Error 3.35 |
p-value: 0.02694795% CI: [-18.4, 0.2]ANCOVA
Secondary
Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)
Mean Hgb during the evaluation period was defined as the mean of all evaluable Hgb values during the evaluation period (Week 28 to Week 52) including any evaluable unscheduled Hgb values that were taken during this time period. Hemoglobin responders were defined as participants with a mean Hgb during the evaluation period that falls within the Hgb analysis range of 10-11.5 g/dL.
Time frame: Week 28 to Week 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daprodustat | Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52) | 903 Participants |
| rhEPO | Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52) | 866 Participants |
p-value: 0.036795% CI: [-0.1, 7.1]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis)
Number of participants with adjudicated MACE or hospitalization for heart failure (recurrent events analysis) is presented, categorized by number of occurrences of adjudicated MACE or hospitalization for heart failure per participant.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Daprodustat | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 0 | 1062 Participants |
| Daprodustat | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 1 | 315 Participants |
| Daprodustat | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 2 | 72 Participants |
| Daprodustat | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 3 | 25 Participants |
| Daprodustat | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 4 | 3 Participants |
| Daprodustat | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 5 | 4 Participants |
| Daprodustat | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 6 | 4 Participants |
| Daprodustat | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 7 | 0 Participants |
| Daprodustat | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 8 | 0 Participants |
| Daprodustat | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 9 | 1 Participants |
| Daprodustat | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 10 | 1 Participants |
| rhEPO | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 5 | 4 Participants |
| rhEPO | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 0 | 1044 Participants |
| rhEPO | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 8 | 1 Participants |
| rhEPO | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 1 | 300 Participants |
| rhEPO | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 6 | 3 Participants |
| rhEPO | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 2 | 88 Participants |
| rhEPO | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 10 | 1 Participants |
| rhEPO | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 3 | 22 Participants |
| rhEPO | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 7 | 2 Participants |
| rhEPO | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 4 | 11 Participants |
| rhEPO | Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis) | Occurrences per participant: 9 | 1 Participants |
p-value: 0.035195% CI: [0.8, 1.01]Chi-squared
p-value: 0.325895% CI: [0.85, 1.11]Chi-squared
p-value: 0.015895% CI: [0.58, 0.98]Chi-squared
p-value: 0.098195% CI: [0.47, 1.17]Chi-squared
p-value: 0.325895% CI: [0.85, 1.11]Chi-squared
p-value: 0.005895% CI: [0.6, 0.94]Chi-squared
Secondary
Number of Participants With at Least One BP Exacerbation Event During Study
BP exacerbation was defined as: SBP \>= 25 mmHg increased from Baseline or SBP \>=180 mmHg; DBP \>=15 mmHg increased from Baseline or DBP \>=110 mmHg. Number of participants with at least one BP exacerbation event is presented.
Time frame: Day 1 to end of study (3.9 person-years for follow-up time period)
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daprodustat | Number of Participants With at Least One BP Exacerbation Event During Study | 1191 Participants |
| rhEPO | Number of Participants With at Least One BP Exacerbation Event During Study | 1186 Participants |
Secondary
Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria
Percentage of participants permanently stopping randomized treatment due to meeting rescue criteria has been presented.
Time frame: Day 1 to 45.1 months
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria | 3.6 Percentage of participants |
| rhEPO | Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria | 3.6 Percentage of participants |
p-value: 0.577295% CI: [0.71, 1.52]Wald test
Secondary
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis
Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / \[Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) - Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)\].
Time frame: Week 28 to Week 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daprodustat | Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis | 60.9 Percentage of days |
| rhEPO | Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis | 59.4 Percentage of days |
95% CI: [0, 3.86]
Secondary
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority Analysis
Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / \[Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) - Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)\].
Time frame: Week 28 to Week 52
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daprodustat | Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority Analysis | 60.9 Percentage of days |
| rhEPO | Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority Analysis | 59.4 Percentage of days |
p-value: 0.080595% CI: [0.49, 0.54]van Elteren test
Secondary
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Non-inferiority Analysis
Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / \[Earlier of (Date of the last evaluable Hgb value, End of study date)- Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)\].
Time frame: Week 28 to end of study (3.9 person-years for follow-up time period)
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daprodustat | Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Non-inferiority Analysis | 60.9 Percentage of days |
| rhEPO | Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Non-inferiority Analysis | 57.7 Percentage of days |
95% CI: [0.28, 4.05]
Secondary
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Superiority Analysis
Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / \[Earlier of (Date of the last evaluable Hgb value, End of study date)- Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)\].
Time frame: Week 28 to end of study (3.9 person-years for follow-up time period)
Population: All Randomized (ITT) Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daprodustat | Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Superiority Analysis | 60.9 Percentage of days |
| rhEPO | Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Superiority Analysis | 57.7 Percentage of days |
p-value: 0.013995% CI: [0.5, 0.55]van Elteren test
Secondary
Time to First Occurrence of Adjudicated All-Cause Mortality During Vital Status for Follow-up Time Period
Time to first occurrence of adjudicated all-cause mortality was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the vital status for follow-up time period.
Time frame: Up to 3.9 person-years for vital status follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of Adjudicated All-Cause Mortality During Vital Status for Follow-up Time Period | 8.32 Events per 100 person years |
| rhEPO | Time to First Occurrence of Adjudicated All-Cause Mortality During Vital Status for Follow-up Time Period | 8.59 Events per 100 person years |
p-value: 0.328195% CI: [0.82, 1.13]Wald test
Secondary
Time to First Occurrence of Adjudicated CV Mortality During CV Events Follow-up Time Period
Time to first occurrence of adjudicated CV mortality was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of Adjudicated CV Mortality During CV Events Follow-up Time Period | 3.31 Events per 100 person years |
| rhEPO | Time to First Occurrence of Adjudicated CV Mortality During CV Events Follow-up Time Period | 3.46 Events per 100 person years |
p-value: 0.355395% CI: [0.74, 1.23]Wald test
Secondary
Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI During CV Events Follow-up Time Period
Time to first occurrence of adjudicated CV mortality or non-fatal MI was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI During CV Events Follow-up Time Period | 5.98 Events per 100 person years |
| rhEPO | Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI During CV Events Follow-up Time Period | 6.79 Events per 100 person years |
p-value: 0.087295% CI: [0.73, 1.06]Wald test
Secondary
Time to First Occurrence of Adjudicated Hospitalization for Heart Failure During CV Events Follow-up Time Period
Time to first occurrence of adjudicated hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of Adjudicated Hospitalization for Heart Failure During CV Events Follow-up Time Period | 3.30 Events per 100 person years |
| rhEPO | Time to First Occurrence of Adjudicated Hospitalization for Heart Failure During CV Events Follow-up Time Period | 3.01 Events per 100 person years |
p-value: 0.765895% CI: [0.84, 1.45]Wald test
Secondary
Time to First Occurrence of Adjudicated MACE During CV Events Follow-up Time Period: Superiority Analysis
Time to MACE defined as the time to first occurrence of CEC adjudicated MACE was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariate. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of Adjudicated MACE During CV Events Follow-up Time Period: Superiority Analysis | 11.07 Events per 100 person years |
| rhEPO | Time to First Occurrence of Adjudicated MACE During CV Events Follow-up Time Period: Superiority Analysis | 11.86 Events per 100 person years |
p-value: 0.15612395% CI: [0.81, 1.07]Wald test
Secondary
Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure During CV Events Follow-up Time Period
Time to first occurrence of adjudicated MACE or hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure During CV Events Follow-up Time Period | 12.98 Events per 100 person years |
| rhEPO | Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure During CV Events Follow-up Time Period | 13.38 Events per 100 person years |
p-value: 0.32579795% CI: [0.85, 1.11]Wald test
Secondary
Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic Events During CV Events Follow-up Time Period
Time to first occurrence of adjudicated MACE or hospitalization for heart failure or thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic Events During CV Events Follow-up Time Period | 17.74 Events per 100 person years |
| rhEPO | Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic Events During CV Events Follow-up Time Period | 19.50 Events per 100 person years |
p-value: 0.05495% CI: [0.81, 1.02]Wald test
Secondary
Time to First Occurrence of Adjudicated MACE or Thromboembolic Event During CV Events Follow-up Time Period
Time to first occurrence of adjudicated MACE or thromboembolic event (vascular access thrombosis, symptomatic deep vein thrombosis or symptomatic pulmonary embolism) was analyzed using a Cox proportional hazards regression model with with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of Adjudicated MACE or Thromboembolic Event During CV Events Follow-up Time Period | 15.84 Events per 100 person years |
| rhEPO | Time to First Occurrence of Adjudicated MACE or Thromboembolic Event During CV Events Follow-up Time Period | 17.85 Events per 100 person years |
p-value: 0.02353995% CI: [0.78, 1]Wald test
Secondary
Time to First Occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) During CV Events Follow-up Time Period
Time to first occurrence of adjudicated MI (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) During CV Events Follow-up Time Period | 3.34 Events per 100 person years |
| rhEPO | Time to First Occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) During CV Events Follow-up Time Period | 4.08 Events per 100 person years |
p-value: 0.052495% CI: [0.63, 1.04]Wald test
Secondary
Time to First Occurrence of Adjudicated Stroke (Fatal and Non-Fatal) During CV Events Follow-up Time Period
Time to first occurrence of adjudicated stroke (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of Adjudicated Stroke (Fatal and Non-Fatal) During CV Events Follow-up Time Period | 1.23 Events per 100 person years |
| rhEPO | Time to First Occurrence of Adjudicated Stroke (Fatal and Non-Fatal) During CV Events Follow-up Time Period | 1.48 Events per 100 person years |
p-value: 0.192795% CI: [0.56, 1.25]Wald test
Secondary
Time to First Occurrence of Adjudicated Thromboembolic Events During CV Events Follow-up Time Period
Time to first occurrence of adjudicated thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of Adjudicated Thromboembolic Events During CV Events Follow-up Time Period | 5.66 Events per 100 person years |
| rhEPO | Time to First Occurrence of Adjudicated Thromboembolic Events During CV Events Follow-up Time Period | 6.75 Events per 100 person years |
p-value: 0.042595% CI: [0.69, 1.02]Wald test
Secondary
Time to First Occurrence of All-Cause Hospitalization During CV Events Follow-up Time Period
All-cause hospitalization events were hospital admissions recorded on the Hospitalization electronic case report form (eCRF) with a hospitalization duration \>=24 hours. Time to first occurrence of all-cause hospitalization was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of All-Cause Hospitalization During CV Events Follow-up Time Period | 43.92 Events per 100 person years |
| rhEPO | Time to First Occurrence of All-Cause Hospitalization During CV Events Follow-up Time Period | 46.03 Events per 100 person years |
p-value: 0.15495% CI: [0.87, 1.04]Wald test
Secondary
Time to First Occurrence of All-Cause Hospital Re-admission Within 30 Days During CV Events Follow-up Time Period
All-cause hospital re-admissions within 30days are defined as hospital admissions recorded on hospitalization eCRF with hospitalization duration of \>=24 hours and admission date within 30days following previous discharge date of all-cause hospitalization event, where previous hospitalization was \>=24 hours. Time to first occurrence of all-cause hospital re-admission within 30days was analyzed using Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date)+1. Incidence rate per 100person years calculated as(100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time frame: Up to 3.9 person-years for CV follow-up time period
Population: All Randomized (ITT) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Time to First Occurrence of All-Cause Hospital Re-admission Within 30 Days During CV Events Follow-up Time Period | 8.86 Events per 100 person years |
| rhEPO | Time to First Occurrence of All-Cause Hospital Re-admission Within 30 Days During CV Events Follow-up Time Period | 9.67 Events per 100 person years |
p-value: 0.124495% CI: [0.77, 1.07]Wald test