Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT05682326 | Anemia Studies in CKD: Erythropoiesis Via a Novel PHI Daprodustat - Pediatric (ASCEND-P) | PHASE3 | COMPLETED | 4 | — | — | Sep 6, 2023 | Mar 17, 2025 | Nov 10, 2025 | 4 | Japan, South Korea |
| NCT03400033 | Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat-Three-times Weekly Dosing in Dialysis (ASCEND-TD) | PHASE3 | COMPLETED | 407 | — | — | Sep 5, 2018 | Jun 19, 2020 | Jul 12, 2021 | 91 | United States, Argentina +11 |
| NCT03409107 | Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat in Non-Dialysis Subjects Evaluating Hemoglobin (Hgb) and Quality of Life (ASCEND-NHQ) | PHASE3 | COMPLETED | 614 | — | — | Mar 5, 2018 | Oct 7, 2020 | Apr 2, 2024 | 168 | United States, Argentina +12 |
| NCT03029208 | Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat-in Incident Dialysis (ASCEND-ID) | PHASE3 | COMPLETED | 312 | — | — | May 11, 2017 | Sep 24, 2020 | Oct 20, 2021 | 111 | United States, Argentina +13 |
| NCT02879305 | Anemia Studies in Chronic Kidney Disease: Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Dialysis (ASCEND-D) | PHASE3 | COMPLETED | 2,964 | — | — | Sep 28, 2016 | Nov 9, 2020 | Dec 3, 2021 | 462 | United States, Argentina +33 |
| NCT02876835 | Anemia Studies in Chronic Kidney Disease: Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) | PHASE3 | COMPLETED | 3,872 | — | — | Sep 27, 2016 | Apr 19, 2021 | Apr 2, 2024 | 574 | United States, Argentina +37 |
| NCT03457701 | Anemia Studies in CKD: Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat- Iron (ASCEND: Fe) | PHASE2 | COMPLETED | 15 | — | — | Jul 30, 2019 | Jul 5, 2022 | Mar 27, 2024 | 3 | United States |
| NCT03029247 | Anemia Study in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat-Blood Pressure (ASCEND-BP) | PHASE2 | COMPLETED | 105 | — | — | Jul 27, 2017 | Jul 9, 2020 | Jun 3, 2021 | 11 | United States |
| NCT04640311 | Comparison of Daprodustat Formulations Produced by Two Methods of Manufacture for Bioequivalence and Dissolution in Healthy Participants | PHASE1 | COMPLETED | 259 | — | — | Dec 18, 2020 | May 18, 2021 | Apr 10, 2025 | 4 | United States |
| NCT03493386 | Daprodustat Bioequivalence and Food Effect Study | PHASE1 | COMPLETED | 64 | — | — | Apr 24, 2018 | Jun 9, 2018 | Jul 8, 2020 | 1 | Japan |
| NCT03223337 | Daprodustat Hepatic Impairment Study | PHASE1 | COMPLETED | 37 | — | — | Jul 24, 2017 | Aug 20, 2018 | Sep 4, 2019 | 2 | United States |
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other situations as per medical and scientific judgement of the Investigator.
AESIs are AEs of scientific interest specific to the drug class as per investigator assessment. AESI included: Death, Myocardial Infarction (MI), stroke, Heart Failure (HF), thromboembolic events, thrombosis of vascular access, Thrombosis and/or tissue ischemia secondary to excessive erythropoiesis, New diagnosis of hypertension or worsening of existing hypertension, Cancer related mortality and tumor progression and recurrence, Esophageal and gastric erosions. Number of participants with any AESIs have been presented.
All AEs leading to study intervention discontinuation were collected. Number of participants with any AEs leading to study intervention discontinuation have been presented
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, the missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputations. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date, including those from unscheduled visits. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Analysis was performed using the Analysis of Covariance (ANCOVA) model with terms for treatment, Baseline hemoglobin, and region.
Blood samples were collected at given time points from participants for hemoglobin measurements. Evaluation period hemoglobin value was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 24 to Week 28 inclusive). For the primary analysis, the missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputations. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using the Analysis of Covariance (ANCOVA) model with terms for treatment, Baseline hemoglobin, and region.
Blood samples were collected from participants for Hgb measurement. Hgb during the evaluation period was defined as the mean of all available post-randomization Hgb values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis missing post-Baseline Hgb values were imputed using pre-specified multiple imputations. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. An analysis of covariance (ANCOVA) model including randomization stratification factors Baseline Hgb and treatment was performed to obtain a point estimate and two-sided 95 percent (%) confidence interval (CI) for the treatment difference (daprodustat-darbepoetin alfa).
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.
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 to MACE defined as 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, current erythropoiesis-stimulating agents (ESA) use at randomization 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 \[\*\] 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.
Blood samples were collected from participants for Hgb measurements. Hgb during the evaluation period was defined as the mean of all available post-randomization Hgb values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis missing post-Baseline Hgb 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. Analysis was performed using the Analysis of covariance (ANCOVA) model with terms for treatment, Baseline Hgb, current ESA use and region.
Blood samples were collected at indicated time points for analysis of fractional oral iron absorption following treatment with Daprodustat and rhEPO. Adjusted mean and 95 percent (%) confidence interval (CI) has been presented.
The effect of daprodustat and epoetin alfa on blood pressure was compared using ABPM after 8 weeks of Hgb maintenace therapy on Day 57. Analysis was based on "analysis of covariance (ANCOVA) with terms for treatment, prior erythropoiesis-stimulating agent (ESA) dose (low/high), post-Hemodialysis dependent (HD)/pre-AC 1 SBP, difference between post-HD/pre-AC 2 SBP and post-HD/pre-AC 1 SBP and treatment by difference in post-HD SBP between AC 1 and 2 interaction." Least square (LS) mean of 6 hour average SBP post AC2 on Day 57 and its corresponding standard error has been presented.
Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods. The geometric coefficient of variation is model adjusted and is a within-participant coefficient of variation. Analysis was performed using a mixed effect model.
Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods. The geometric coefficient of variation is model adjusted and is a within-participant coefficient of variation. Analysis was performed using a mixed effect model.
Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods. The geometric coefficient of variation is model adjusted and is a within-participant coefficient of variation. Analysis was performed using a mixed effect model.
Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods. The geometric coefficient of variation is model adjusted and is a within-participant coefficient of variation. Analysis was performed using a mixed effect model.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. PK population comprised of all participants in the Safety population (all randomized participants) who received at least one dose of study intervention) who had at least 1 non-missing PK assessment.
Blood samples were collected at indicated timepoints and pharmacokinetic (PK) analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population for whom a pharmacokinetic sample was obtained and analyzed.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2) , GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818, GSK2506102, GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods. Unbound fraction is the percentage of unbound drug in plasma calculated as unbound concentration divided by total concentration.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites (GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13)). Pharmacokinetic parameters were determined using standard non-compartmental methods. Unbound fraction is the percentage of unbound drug in plasma calculated as unbound concentration divided by total concentration.
| Arm | Type | Description |
|---|---|---|
| Daprodustat | EXPERIMENTAL | All participants will receive daprodustat for up to 52 weeks. |
| Epoetin alfa | ACTIVE_COMPARATOR | Subjects randomized to this arm will receive matching placebo tablets to daprodustat orally three-times weekly and Epoetin alfa by IV route for the 52 weeks treatment period. |
| Daprodustat receivers | EXPERIMENTAL | Participants will receive oral daprodustat once daily |
| Placebo receivers | PLACEBO_COMPARATOR | Participants will receive oral placebo once daily |
| Daprodustat treated anemic subjects | EXPERIMENTAL | Subjects will receive oral daprodustat once daily. |
| Darbepoetin alfa treated anemic subjects | ACTIVE_COMPARATOR | Subjects will receive darbepoetin alfa subcutaneously or intravenously. |
| rhEPO | ACTIVE_COMPARATOR | Participants on peritoneal dialysis (PD) will be administered darbepoetin alfa subcutaneously (SC) and participants on hemodialysis (HD) will be administered epoetin alfa intravenously (IV). |
| Darbepoetin alfa | ACTIVE_COMPARATOR | Participants will be administered darbepoetin alfa subcutaneously (SC). |
| rhEPO+57Fe followed by Daprodustat+58Fe | EXPERIMENTAL | Participants will be randomly assigned to remain on their current therapy (either epoetin alfa or darbepoetin alfa) in Treatment Period 1. For assessment of incorporation of iron into erythrocytes, participants will be administered ferrous sulfate containing a stable isotope of iron (57Fe) orally in a randomized fashion following 2 weeks of administration of randomized study treatment. At Day 29 participants will be crossed over to receive Daprodustat in Treatment Period 2. At 2 weeks following initiation of dosing in Treatment Period 2, participants will again be administered ferrous sulfate containing the stable iron isotope (58Fe) orally. Participants will be advised to maintain use of oral iron supplementation (except ferric citrate) and acid-reducing agents (example: Histamine \[H2\] receptor antagonists, proton pump inhibitors, antacids) at a consistent dosage and frequency. |
| rhEPO+58Fe followed by Daprodustat+57Fe | EXPERIMENTAL | Participants will be randomly assigned to remain on their current therapy (either epoetin alfa or darbepoetin alfa) in Treatment Period 1. For assessment of incorporation of iron into erythrocytes, participants will be administered ferrous sulfate containing a stable isotope of iron (58Fe) orally in a randomized fashion following 2 weeks of administration of randomized study treatment. At Day 29 participants will be crossed over to receive Daprodustat in Treatment Period 2. At 2 weeks following initiation of dosing in Treatment Period 2, participants will again be administered ferrous sulfate containing the stable iron isotope (57Fe) orally. Participants will be advised to maintain use of oral iron supplementation (except ferric citrate) and acid-reducing agents (example: H2 receptor antagonists, proton pump inhibitors, antacids) at a consistent dosage and frequency. |
| Daprodustat+57Fe followed by rhEPO+58Fe | EXPERIMENTAL | Participants will be randomly assigned to receive Daprodustat in Treatment Period 1. For assessment of incorporation of iron into erythrocytes, participants will be administered ferrous sulfate containing a stable isotope of iron (57Fe) orally in a randomized fashion following 2 weeks of administration of randomized study treatment. At Day 29 participants will be crossed over to receive rhEPO (either epoetin alfa or darbepoetin alfa) in Treatment Period 2. At 2 weeks following initiation of dosing in Treatment Period 2, participants will again be administered ferrous sulfate containing the stable iron isotope (58Fe) orally. Participants will be advised to maintain use of oral iron supplementation (except ferric citrate) and acid-reducing agents (example: H2 receptor antagonists, proton pump inhibitors, antacids) at a consistent dosage and frequency. |
| Daprodustat+58Fe followed by rhEPO+57Fe | EXPERIMENTAL | Participants will be randomly assigned to receive Daprodustat in Treatment Period 1. For assessment of incorporation of iron into erythrocytes, participants will be administered ferrous sulfate containing a stable isotope of iron (58Fe) orally in a randomized fashion following 2 weeks of administration of randomized study treatment. At Day 29 participants will be crossed over to receive rhEPO (either epoetin alfa or darbepoetin alfa) in Treatment Period 2. At 2 weeks following initiation of dosing in Treatment Period 2, participants will again be administered ferrous sulfate containing the stable iron isotope (57Fe) orally. Participants will be advised to maintain use of oral iron supplementation (except ferric citrate) and acid-reducing agents (example: H2 receptor antagonists, proton pump inhibitors, antacids) at a consistent dosage and frequency. |
| Participants receiving Epoetin alfa | ACTIVE_COMPARATOR | On Day 1, participants will undergo 24-hour Acute Challenge 1, in which participants will receive a single dose of 100 U/kg epoetin alfa IV. After completing Acute Challenge 1, participants will enter in an 8-week Hgb maintenance period. At the end of Hgb maintenance period, on Day 57, Acute Challenge 2 will be performed utilizing the same treatment dose administered in Acute Challenge 1. |
| Participants receiving Daprodustat | EXPERIMENTAL | On Day 1, participants will undergo 24-hour Acute Challenge 1, in which participants will receive 24 mg daprodustat. After completing Acute Challenge 1, participants will enter an 8-week Hgb maintenance period. At the end of Hgb maintenance period, on Day 57, Acute Challenge 2 will be performed utilizing the same treatment dose administered in Acute Challenge 1. |
| Part A: Daprodustat Dissolution 1/Dissolution 2/Reference | EXPERIMENTAL | - |
| Part A: Daprodustat Dissolution 2/Reference/Dissolution 1 | EXPERIMENTAL | - |
| Part A: Daprodustat Reference/Dissolution 1/Dissolution 2 | EXPERIMENTAL | - |
| Part B: Daprodustat Process 1/ Process 2 | EXPERIMENTAL | - |
| Part B: Daprodustat Process 2/ Process 1 | EXPERIMENTAL | - |
| Treatment Group A: Part 1 | EXPERIMENTAL | Subjects will be randomized to receive single dose of two tablets of 2 mg daprodustat in Period 1 and in Period 2 subjects will receive single dose of 4 mg daprodustat. There will be a wash-out period of 5 days between the Periods. |
| Treatment Group B: Part 1 | EXPERIMENTAL | Subjects will be randomized to receive single dose of 4 mg daprodustat in Period 1 and in Period 2 subjects will receive single dose of two tablets of 2 mg daprodustat. There will be a wash-out period of 5 days between the Periods. |
| Treatment Group C: Part 2 | EXPERIMENTAL | Subjects will be randomized to receive single dose of 4 mg daprodustat in fed state during Period 1 and in Period 2 subjects will receive single dose of 4 mg daprodustat in fasted state. There will be a wash-out period of 5 days between the Periods. |
| Treatment Group D: Part 2 | EXPERIMENTAL | Subjects will be randomized to receive single dose of 4 mg daprodustat in fasted state during period 1 and in Period 2 subjects will receive single dose of 4 mg daprodustat in fed state. There will be a wash-out period of 5 days between the Periods. |
| Subjects with moderate hepatic impairment: Part 1 | EXPERIMENTAL | Approximately 8 subjects with moderate hepatic impairment will receive 6 mg of daprodustat as a single oral dose in the fasted state. This group will include at least one subject with a Child-Pugh score of 7, one with a score of 8 and one with a score of 9. The group will also include at least one female and at least one male subject. |
| Matched Healthy controls: Part 1 | ACTIVE_COMPARATOR | Approximately 8 healthy controls, matched in gender, age and BMI to subjects with moderate hepatic impairment, will receive 6 mg of daprodustat as a single oral dose in the fasted state. The group will include at least one female and at least one male subject. |
| Subjects with either mild or severe hepatic impairment: Part 2 | EXPERIMENTAL | Approximately 8 subjects with mild or severe hepatic impairment will receive 6 mg of daprodustat as a single oral dose in the fasted state. This group will include at least one subject with a Child-Pugh score of 5 and one with a score of 6 for mild hepatic impairment and at least one subject with a Child-Pugh score of 10 or 11 and one with a score of 12 or 13 for severe hepatic impairment. The group will also include at least one female and at least one male subject. |
| Matched healthy controls: Part 2 | ACTIVE_COMPARATOR | Approximately 8 healthy controls, matched in gender, age and BMI to subjects with mild or severe hepatic impairment, will receive 6 mg of daprodustat as a single oral dose in the fasted state. The group will include at least one female and at least one male subject. |
| Name | Type | Description |
|---|---|---|
| Daprodustat | DRUG | Daprodustat will be administered up to Week 52. |
| Daprodustat tablets | DRUG | Round, biconvex, white, film-coated tablet in unit dose strengths 2 and 4 milligrams (7 millimeter tablets), 6, 8 and 10 milligrams (9 millimeter tablets) administered by the oral route. |
| Matching placebo tablets | DRUG | Matching placebo to daprodustat tablets supplied as round, biconvex, white, film-coated tablet in unit dose strengths 2 and 4 milligrams (7 millimeter tablets), 6, 8 and 10 milligrams (9 millimeter tablets) administered by the oral route. |
| Epoetin alfa vials | DRUG | Single-dose, preservative-free vials in unit dose strengths of 2000, 3000, 4000 and 10,000 Units/milliliter administered by the IV route. |
| Saline vials or bags | DRUG | 0.9% sodium chloride saline vials or bags administered by the IV route. |
| Daprodustat (GSK1278863) | DRUG | Daprodustat will be available as 9 millimeter (mm) or 7 mm film-coated tablets. Daprodustat will be administered once daily via oral route and can be taken without regard to food. |
| Placebo | DRUG | Daprodustat matching placebo will be available as 9 mm or 7 mm film coated tablets. Placebo will be administered once daily via oral route and can be taken without regard to food. |
| Iron therapy | DRUG | Iron therapy will be administered if ferritin is \<50 Nano gram per milliliter and/or TSAT is \<15 percent. |
| Darbepoetin alfa | DRUG | Darbepoetin alfa will be supplied as prefilled syringes (PFS) for SC/IV injection available in strengths: 20, 30, 40, 60, 80, 100 and 150 mcg. |
| rhEPO | DRUG | 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. |
| Ferrous sulfate containing the stable iron isotope (57Fe) | DRUG | 57Fe will be available in oral solution. An oral solution will be administered containing 10 mg of 57Fe as ferrous sulfate. |
| Ferrous sulfate containing the stable iron isotope (58Fe) | DRUG | 58Fe will be available in oral solution. An oral solution will be administered containing 3 mg of 58Fe as ferrous sulfate with 7 mg of 56Fe as ferrous sulfate (natural abundance Fe). |
| Epoetin alfa | DRUG | Epoetin alfa will be administered according to local labelling and clinical practice guidelines to keep Hgb in the target range (10.0-11.0 g/dL) |
| Daprodustat 2 mg tablet | DRUG | Daprodustat is available as 2 mg tablet. Subjects will receive daprodustat orally as tablet. A single dose of 2 tablets of 2 mg daprodustat will be administered in a fasted state during Part 1 of the study. |
| Daprodustat 4 mg tablet | DRUG | Daprodustat is available as 4 mg tablet. Subjects will receive daprodustat orally as tablet. A single dose of 4 mg daprodustat will be administered in a fasted state during Part 1 and in fed and fasted state in Part 2 of the study. |
Inclusion Criteria: * Participant must be 3 months to less than (\<)18 years of age. * Anemia associated with CKD stage 3, 4, 5 (not on dialysis) or who have dialysis-dependent CKD, defined as Hgb 7.0 to 11.0 g/dL (if not using erythropoiesis stimulating agents \[ESAs\]) or Hgb 9.5 to 12.0 g/dL if ...