Anaemia
Conditions
Keywords
CKD, EPO, rhEPO, Hemodialysis dependent, Daprodustat
Brief summary
This Phase 3 study in hemodialysis-dependent subjects with anemia will evaluate the efficacy and safety of daprodustat administered three-times weekly compared to epoetin alfa, the current standard of care. This study includes a 4 week Screening Period, a 52 week Treatment Period and a 4 to 6 week follow-up period. Each subject will remain in the study for up to 62 weeks. Approximately 402 subjects will be randomized to receive either daprodustat three times weekly or epoetin alfa three-times weekly or once weekly, depending on dose level.
Interventions
DRUGDaprodustat tablets
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 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.
DRUGEpoetin alfa vials
Single-dose, preservative-free vials in unit dose strengths of 2000, 3000, 4000 and 10,000 Units/milliliter administered by the IV route.
DRUGSaline vials or bags
0.9% sodium chloride saline vials or bags administered by the IV route.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double-blind study, in which the subject, investigator, site staff and the sponsor will remain blinded to each subjects study treatment assignment throughout the course of the study, with the exception of a limited number of unblinded site staff who are necessary to maintain the blind, as well as a limited number of sponsor staff.
Intervention model description
Subjects will be randomized to receive either daprodustat or epoetin alfa in a parallel manner. .
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Subject must be 18 to 99 years of age inclusive, at the time of signing the informed consent. * Use of any approved rhEPO or analog for at least 8 weeks prior to the screening visit and continuing during the screening period until randomization (Day 1). * Hgb concentration (measured by HemoCue) within the following range: Week -4: Hgb 8 to 11.5 grams/deciliter (5 to 7.1 millimoles/liter). If Hgb is 11.6 to 11.9 grams/deciliter (7.2 to 7.4 millimoles/liter), up to two retests are allowed; the retest value must be between 8 to 11.5 grams/deciliter (5 to 7.1 millimoles/liter). Day 1: Hgb 8 to 11 grams/deciliter (5 to 6.8 millimoles/liter) and receiving at least the minimum rhEPO or analog dose 3. Hgb\>11 to 11.5 grams/deciliter (6.8 to 7.1 millimoles/liter) and receiving greater than the minimum rhEPO or analog dose 3. * On hemodialysis (including hemofiltration or hemodiafiltration) \>90 days prior to screening and continuing during the screening period. * On hemodialysis (in-center) \>=3 times per week. * Male and female subjects are eligible. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP), or A WOCBP who agrees to follow the contraceptive guidance from at least 28 days prior to first dose of study treatment and for at least 28 days after the last dose of study treatment. * Capable of giving signed informed consent. * In France, a subject will be eligible for inclusion in this study if he or she is either affiliated to or beneficiary of a social security category.
Exclusion criteria
* Planned living-related or living-unrelated kidney transplant within 52 weeks after randomization (Day 1). * Ferritin: \<=100 nanograms/milliliter (\<=100 micrograms/liter), at screening. * Transferrin saturation (TSAT): \<=20 percent, at screening. If TSAT is 18 to 20 percent, then a retest using a new blood sample can be obtained within 7 days of the final laboratory report; the final retest value must be \>20 percent to confirm eligibility. * Aplasias: History of bone marrow aplasia or pure red cell aplasia. * Conditions, other than anemia of CKD, which can affect erythropoiesis. * Myocardial infarction (MI) or acute coronary syndrome within 8 weeks prior to screening through to randomization (Day 1). * Stroke or transient ischemic attack within 8 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 as determined by the investigator that would contraindicate the use of rhEPO. * Bazett's correction of QTc interval (QTcB): at Day 1: QTcB \>500 milliseconds, or QTcB \>530 milliseconds in subjects with bundle branch block. There is no QTc (corrected QT) exclusion for subjects with a predominantly ventricular paced rhythm. * Liver Disease: presence of any one of the following liver-related laboratory values or conditions, at screening, is exclusionary: ALT \>2x upper limit of normal (ULN); Bilirubin \>1.5x ULN; or Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. * Evidence of actively bleeding gastric, duodenal or esophageal ulcer disease OR clinically significant gastro intestinal bleeding \<= 8 weeks prior to screening through to randomization (Day 1). * History of malignancy within 2 years prior to screening through to randomization (Day 1), currently receiving treatment for cancer, or complex kidney cyst (e.g., Bosniak Category IIF, III or IV) \>3 centimeters. * Use of a strong inhibitor of Cytochrome P4502C8 \[CYP2C8\] (e.g. gemfibrozil) or a strong inducer of CYP2C8 (e.g. rifampin/rifampicin). * History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product (daprodustat) or epoetin alfa. * Use of another investigational agent within 30 days or within five half-lives of the investigational agent (whichever is longer) or currently participating in a study of an investigational device prior to screening through to randomization (Day 1). * Any prior treatment with daprodustat for treatment duration of \>30 days. * 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 |
|---|---|---|
| Mean Change From Baseline in Hemoglobin Levels Over the 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, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin Levels at Week 52 | Baseline (Pre-dose on Day 1) and Week 52 | Blood samples were collected from participants for hemoglobin measurements. 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 post-randomization visit value minus Baseline value. Analysis was performed using a mixed model repeated measures (MMRM) model fitted to hemoglobin data collected after Baseline up to Week 52, excluding values collected during the stabilization period (Day 1 to Week 28). The model included factors for treatment, time, region, Baseline hemoglobin and Baseline hemoglobin by time and treatment by time interaction terms. |
| Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52) | Week 28 to Week 52 | Participants received treatment during the study to achieve or maintain hemoglobin level in the target range. Percentage of time for which hemoglobin level was maintained within the analysis range (10 to 11.5 grams/deciliter) has been presented. |
| Number of Hemoglobin Responders in the Hemoglobin Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52) | Week 28 to Week 52 | Mean hemoglobin during the evaluation period was defined as the mean of all evaluable hemoglobin values during the evaluation period (Week 28 to Week 52) including any evaluable unscheduled hemoglobin values that were taken during this time period. Hemoglobin responders were defined as the number of participants with a mean hemoglobin during the evaluation period that falls within the hemoglobin analysis range of 10-11.5 grams/deciliter. |
| Percentage of Participants Permanently Stopping Study Treatment Due to Meeting Rescue Criteria | Up to Week 52 | Percentage of participants permanently stopping study treatment due to meeting rescue criteria has been presented. |
| Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at Week 52 | Baseline (Week -4 ) and Week 52 | Measurements for SBP, DBP and MAP were taken with the participant in a semi-supine or seated position in the dialysis chair after at least a 5-minute rest period. MAP is the average BP in an individual's arteries during a single cardiac cycle. 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 on-treatment visit value minus Baseline value. Analysis was performed using MMRM model with treatment group, time, region, Baseline value, Baseline value\*time, treatment group\*time as variables. |
| Mean Average Monthly On-treatment Intravenous (IV) Iron Dose Per Participant | Day 1 to Week 52 | Average monthly IV iron dose (mg) per participant during Day 1 to Week 52 was determined by calculating the total IV iron dose per participant from Day 1 to Week 52 while the participant was on study treatment and dividing by (the number of days the participant was on study treatment divided by 30.4375 days). Analysis was performed using the ANCOVA model with terms for treatment, Baseline monthly IV iron dose, and region. |
| Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years | Up to 52 weeks | BP exacerbation event is defined (based on post-dialysis BP) as SBP \>=25 mmHg increased from Baseline or SBP \>=180 mmHg; or 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. |
| Number of Participants With at Least One BP Exacerbation Event During the Study | Up to 52 weeks | BP exacerbation (based on post-dialysis BP) is defined as: SBP \>= 25 mmHg increased from Baseline or SBP \>=180mmHg; or DBP \>=15 mmHg increase from Baseline or DBP \>=110 mmHg. Number of participants with at least 1 BP exacerbation event have been reported. |
| Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S) | Baseline (Pre-dose on Day 1) and Weeks 8, 12, 28, 52 | The PGI-S is a 1-item questionnaire designed to assess participant's impression of disease severity of their anemia of Chronic kidney disease (CKD). It is measured on a 5-point disease severity scale ranging from 0 (absent) to 4 (very severe), higher score indicates more disease severity. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date, including those from unscheduled visits. Change from Baseline in on-treatment PGI-S scores was defined as the on-treatment visit value minus Baseline value. Analysis was performed using MMRM model fitted from Baseline up to Week 52 with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions. |
| Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Pre-dose on Day 1; Pre-dose and at 0.5, 1, 2, 3 hours post-dose on any one post-Baseline visit day between Week 8 and Week 52 | Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat (GSK1278863) and its metabolites: GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13). |
| Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Pre-dose on Day 1; Pre-dose and at 0.5, 1, 2, 3 hours post-dose on any one post-Baseline visit day between Week 8 and Week 52 | Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat (GSK1278863) and its metabolites: GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13). |
| Change From Baseline in SBP, DBP and MAP at End of Treatment | Baseline (Week -4) and end of treatment (last on-treatment value until Week 52) | Measurements for SBP, DBP and MAP were taken with the participant in a semi-supine or seated position in the dialysis chair after at least a 5-minute rest period. MAP is the average BP in an individual's arteries during a single cardiac cycle. 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 last on-treatment visit value minus Baseline value. Analysis was performed using ANCOVA model with terms for treatment group, region and Baseline value. Adjusted mean and standard error have been presented. |
Countries
Argentina, Australia, Brazil, Canada, France, Italy, Poland, Romania, Russia, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
This was a multicenter study conducted at 90 centers in 13 countries. Participants were randomized to receive either Daprodustat or Epoetin alfa.
Pre-assignment details
A total of 595 participants were screened, of which 188 were screen failures. A total of 407 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Daprodustat Participants received daprodustat tablets with titrated dose levels ranging from 2, 4, 8, 12, 16, 20, 24, 32 and 48 milligrams (mg) orally three-times weekly up to 52 weeks. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (10 to 11 grams per deciliter \[g/dL\]). In order to maintain the study blind, participants also received saline intravenous (IV) injection once weekly or three-times weekly depending on dose level, up to 52 weeks as an inactive treatment for the IV formulation. All participants were followed up at 4 to 6 weeks after last dose. | 270 |
| Epoetin Alfa Participants received epoetin alfa with titrated dose levels ranging from 1500 Units to 60,000 Units total weekly dose and administered as IV injection once weekly or three-times weekly depending on dose level up to 52 weeks. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (10 to 11 g/dL). In order to maintain the study blind, participants also received placebo tablets matching to daprodustat orally three-times weekly up to 52 weeks as an inactive treatment for the tablet formulation. All participants were followed up at 4 to 6 weeks after last dose. | 137 |
| Total | 407 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Daprodustat | Epoetin Alfa | Total |
|---|---|---|---|
| Age, Customized 19-64 Years | 167 Participants | 96 Participants | 263 Participants |
| Age, Customized >= 65 Years | 103 Participants | 41 Participants | 144 Participants |
| Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKAN NATIVE | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized ASIAN - CENTRAL/SOUTH ASIAN HERITAGE | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized ASIAN - EAST ASIAN HERITAGE | 16 Participants | 9 Participants | 25 Participants |
| Race/Ethnicity, Customized ASIAN - SOUTH EAST ASIAN HERITAGE | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 49 Participants | 32 Participants | 81 Participants |
| Race/Ethnicity, Customized MIXED RACE | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized MIXED WHITE RACE | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized UNKNOWN | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized WHITE - ARABIC/NORTH AFRICAN HERITAGE | 1 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE | 193 Participants | 90 Participants | 283 Participants |
| Sex: Female, Male Female | 121 Participants | 56 Participants | 177 Participants |
| Sex: Female, Male Male | 149 Participants | 81 Participants | 230 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 18 / 270 | 10 / 136 |
| other Total, other adverse events | 74 / 270 | 42 / 136 |
| serious Total, serious adverse events | 80 / 270 | 47 / 136 |
Outcome results
Primary
Mean Change From Baseline in Hemoglobin Levels Over the 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, 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.
Time frame: Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)
Population: All Randomized (Intent-to-treat \[ITT\]) Population comprised of all randomized participants. Any participant who received a treatment randomization number was considered to have been randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Daprodustat | Mean Change From Baseline in Hemoglobin Levels Over the Evaluation Period (Week 28 to Week 52) | -0.04 Grams per deciliter (g/dL) | Standard Error 0.045 |
| Epoetin Alfa | Mean Change From Baseline in Hemoglobin Levels Over the Evaluation Period (Week 28 to Week 52) | 0.02 Grams per deciliter (g/dL) | Standard Error 0.066 |
95% CI: [-0.21, 0.1]
Secondary
Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years
BP exacerbation event is defined (based on post-dialysis BP) as SBP \>=25 mmHg increased from Baseline or SBP \>=180 mmHg; or 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.
Time frame: Up to 52 weeks
Population: All Randomized (ITT) Population. Only those participants with data available at specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years | 250.45 Events per 100 participant years |
| Epoetin Alfa | Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years | 356.91 Events per 100 participant years |
p-value: 0.009395% CI: [0.52, 0.94]Negative binomial model
Secondary
Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S)
The PGI-S is a 1-item questionnaire designed to assess participant's impression of disease severity of their anemia of Chronic kidney disease (CKD). It is measured on a 5-point disease severity scale ranging from 0 (absent) to 4 (very severe), higher score indicates more disease severity. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date, including those from unscheduled visits. Change from Baseline in on-treatment PGI-S scores was defined as the on-treatment visit value minus Baseline value. Analysis was performed using MMRM model fitted from Baseline up to Week 52 with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions.
Time frame: Baseline (Pre-dose on Day 1) and Weeks 8, 12, 28, 52
Population: All Randomized (ITT) Population. Only those participants with data available at specified time points were analyzed (represented as n=X in the category titles).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S) | Week 8; n=248, 126 | -0.10 Scores on a scale | Standard Error 0.048 |
| Daprodustat | Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S) | Week 12; n=243, 120 | -0.13 Scores on a scale | Standard Error 0.05 |
| Daprodustat | Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S) | Week 28; n=211, 106 | -0.07 Scores on a scale | Standard Error 0.054 |
| Daprodustat | Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S) | Week 52; n=170, 85 | -0.11 Scores on a scale | Standard Error 0.063 |
| Epoetin Alfa | Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S) | Week 52; n=170, 85 | 0.04 Scores on a scale | Standard Error 0.088 |
| Epoetin Alfa | Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S) | Week 8; n=248, 126 | 0.05 Scores on a scale | Standard Error 0.068 |
| Epoetin Alfa | Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S) | Week 28; n=211, 106 | 0.03 Scores on a scale | Standard Error 0.077 |
| Epoetin Alfa | Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S) | Week 12; n=243, 120 | -0.01 Scores on a scale | Standard Error 0.071 |
p-value: 0.032395% CI: [-0.32, 0.01]MMRM
p-value: 0.092195% CI: [-0.29, 0.06]MMRM
p-value: 0.129195% CI: [-0.29, 0.08]MMRM
p-value: 0.085995% CI: [-0.36, 0.06]MMRM
Secondary
Change From Baseline in Hemoglobin Levels at Week 52
Blood samples were collected from participants for hemoglobin measurements. 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 post-randomization visit value minus Baseline value. Analysis was performed using a mixed model repeated measures (MMRM) model fitted to hemoglobin data collected after Baseline up to Week 52, excluding values collected during the stabilization period (Day 1 to Week 28). The model included factors for treatment, time, region, Baseline hemoglobin and Baseline hemoglobin by time and treatment by time interaction terms.
Time frame: Baseline (Pre-dose on Day 1) and Week 52
Population: All Randomized (ITT) Population. Only those participants with data available at specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Daprodustat | Change From Baseline in Hemoglobin Levels at Week 52 | -0.03 Grams per deciliter | Standard Error 0.069 |
| Epoetin Alfa | Change From Baseline in Hemoglobin Levels at Week 52 | 0.11 Grams per deciliter | Standard Error 0.098 |
95% CI: [-0.37, 0.1]
Secondary
Change From Baseline in SBP, DBP and MAP at End of Treatment
Measurements for SBP, DBP and MAP were taken with the participant in a semi-supine or seated position in the dialysis chair after at least a 5-minute rest period. MAP is the average BP in an individual's arteries during a single cardiac cycle. 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 last on-treatment visit value minus Baseline value. Analysis was performed using ANCOVA model with terms for treatment group, region and Baseline value. Adjusted mean and standard error have been presented.
Time frame: Baseline (Week -4) and end of treatment (last on-treatment value until Week 52)
Population: All Randomized (ITT) Population. Only those participants with data available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Change From Baseline in SBP, DBP and MAP at End of Treatment | SBP | -1.4 Millimeter of mercury (mmHg) | Standard Error 1.24 |
| Daprodustat | Change From Baseline in SBP, DBP and MAP at End of Treatment | DBP | -1.8 Millimeter of mercury (mmHg) | Standard Error 0.66 |
| Daprodustat | Change From Baseline in SBP, DBP and MAP at End of Treatment | MAP | -1.7 Millimeter of mercury (mmHg) | Standard Error 0.78 |
| Epoetin Alfa | Change From Baseline in SBP, DBP and MAP at End of Treatment | SBP | -0.9 Millimeter of mercury (mmHg) | Standard Error 1.75 |
| Epoetin Alfa | Change From Baseline in SBP, DBP and MAP at End of Treatment | DBP | -0.8 Millimeter of mercury (mmHg) | Standard Error 0.93 |
| Epoetin Alfa | Change From Baseline in SBP, DBP and MAP at End of Treatment | MAP | -0.8 Millimeter of mercury (mmHg) | Standard Error 1.09 |
p-value: 0.40795% CI: [-4.73, 3.72]ANCOVA
p-value: 0.17995% CI: [-3.29, 1.19]ANCOVA
p-value: 0.26195% CI: [-3.5, 1.78]ANCOVA
Secondary
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at Week 52
Measurements for SBP, DBP and MAP were taken with the participant in a semi-supine or seated position in the dialysis chair after at least a 5-minute rest period. MAP is the average BP in an individual's arteries during a single cardiac cycle. 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 on-treatment visit value minus Baseline value. Analysis was performed using MMRM model with treatment group, time, region, Baseline value, Baseline value\*time, treatment group\*time as variables.
Time frame: Baseline (Week -4 ) and Week 52
Population: All Randomized (ITT) Population. Only those participants with data available at specified 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 Pressure (MAP) at Week 52 | SBP | -3.18 Millimeter of mercury (mmHg) | Standard Error 1.47 |
| Daprodustat | Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at Week 52 | DBP | -2.52 Millimeter of mercury (mmHg) | Standard Error 0.764 |
| Daprodustat | Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at Week 52 | MAP | -2.72 Millimeter of mercury (mmHg) | Standard Error 0.907 |
| Epoetin Alfa | Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at Week 52 | SBP | 0.55 Millimeter of mercury (mmHg) | Standard Error 2.252 |
| Epoetin Alfa | Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at Week 52 | DBP | -0.29 Millimeter of mercury (mmHg) | Standard Error 1.176 |
| Epoetin Alfa | Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at Week 52 | MAP | -0.12 Millimeter of mercury (mmHg) | Standard Error 1.389 |
p-value: 0.08395% CI: [-9.03, 1.56]MMRM
p-value: 0.05795% CI: [-4.99, 0.54]MMRM
p-value: 0.05995% CI: [-5.86, 0.67]MMRM
Secondary
Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13)
Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat (GSK1278863) and its metabolites: GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13).
Time frame: Pre-dose on Day 1; Pre-dose and at 0.5, 1, 2, 3 hours post-dose on any one post-Baseline visit day between Week 8 and Week 52
Population: Pharmacokinetic Population. Only those participants with data available at specified time points were analyzed (represented as n=X in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=7, 19, 51, 59, 45, 28, 16, 3, 3 | 2.0473 Nanograms per milliliter | Geometric Coefficient of Variation 100.05 |
| Daprodustat | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=8, 17, 46, 59, 45, 27, 16, 3, 3 | 1.2731 Nanograms per milliliter | Geometric Coefficient of Variation 57.92 |
| Daprodustat | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 0.8328 Nanograms per milliliter | Geometric Coefficient of Variation 101.92 |
| Daprodustat | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=8, 19, 50, 59, 45, 28, 16, 3, 3 | 2.6298 Nanograms per milliliter | Geometric Coefficient of Variation 60.93 |
| Daprodustat | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=8, 20, 49, 57, 45, 28, 16, 3, 3 | 44.5832 Nanograms per milliliter | Geometric Coefficient of Variation 227.65 |
| Daprodustat | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 3.2020 Nanograms per milliliter | Geometric Coefficient of Variation 81.23 |
| Daprodustat | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=7, 18, 47, 56, 45, 28, 16, 3, 3 | 2.0320 Nanograms per milliliter | Geometric Coefficient of Variation 73.45 |
| Epoetin Alfa | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=7, 18, 47, 56, 45, 28, 16, 3, 3 | 3.2703 Nanograms per milliliter | Geometric Coefficient of Variation 143.75 |
| Epoetin Alfa | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 1.4018 Nanograms per milliliter | Geometric Coefficient of Variation 84.93 |
| Epoetin Alfa | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=7, 19, 51, 59, 45, 28, 16, 3, 3 | 4.0012 Nanograms per milliliter | Geometric Coefficient of Variation 88.64 |
| Epoetin Alfa | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=8, 17, 46, 59, 45, 27, 16, 3, 3 | 2.3676 Nanograms per milliliter | Geometric Coefficient of Variation 84.23 |
| Epoetin Alfa | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=8, 19, 50, 59, 45, 28, 16, 3, 3 | 4.0224 Nanograms per milliliter | Geometric Coefficient of Variation 134.91 |
| Epoetin Alfa | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=8, 20, 49, 57, 45, 28, 16, 3, 3 | 51.9261 Nanograms per milliliter | Geometric Coefficient of Variation 227.59 |
| Epoetin Alfa | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 5.2039 Nanograms per milliliter | Geometric Coefficient of Variation 98.7 |
| Daprodustat 8 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=8, 17, 46, 59, 45, 27, 16, 3, 3 | 3.7348 Nanograms per milliliter | Geometric Coefficient of Variation 131.1 |
| Daprodustat 8 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 7.5220 Nanograms per milliliter | Geometric Coefficient of Variation 131.81 |
| Daprodustat 8 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=7, 18, 47, 56, 45, 28, 16, 3, 3 | 6.3474 Nanograms per milliliter | Geometric Coefficient of Variation 175.79 |
| Daprodustat 8 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=7, 19, 51, 59, 45, 28, 16, 3, 3 | 5.4631 Nanograms per milliliter | Geometric Coefficient of Variation 120.63 |
| Daprodustat 8 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 2.0385 Nanograms per milliliter | Geometric Coefficient of Variation 85.59 |
| Daprodustat 8 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=8, 19, 50, 59, 45, 28, 16, 3, 3 | 6.3826 Nanograms per milliliter | Geometric Coefficient of Variation 198.78 |
| Daprodustat 8 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=8, 20, 49, 57, 45, 28, 16, 3, 3 | 113.4049 Nanograms per milliliter | Geometric Coefficient of Variation 179.69 |
| Daprodustat 12 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=8, 17, 46, 59, 45, 27, 16, 3, 3 | 3.8017 Nanograms per milliliter | Geometric Coefficient of Variation 177.36 |
| Daprodustat 12 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=8, 20, 49, 57, 45, 28, 16, 3, 3 | 143.8790 Nanograms per milliliter | Geometric Coefficient of Variation 233.09 |
| Daprodustat 12 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=8, 19, 50, 59, 45, 28, 16, 3, 3 | 8.9535 Nanograms per milliliter | Geometric Coefficient of Variation 126.76 |
| Daprodustat 12 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=7, 18, 47, 56, 45, 28, 16, 3, 3 | 8.0134 Nanograms per milliliter | Geometric Coefficient of Variation 146.43 |
| Daprodustat 12 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 2.8357 Nanograms per milliliter | Geometric Coefficient of Variation 68.15 |
| Daprodustat 12 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 10.8186 Nanograms per milliliter | Geometric Coefficient of Variation 84.31 |
| Daprodustat 12 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=7, 19, 51, 59, 45, 28, 16, 3, 3 | 8.8488 Nanograms per milliliter | Geometric Coefficient of Variation 80.17 |
| Daprodustat 16 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=8, 19, 50, 59, 45, 28, 16, 3, 3 | 9.5131 Nanograms per milliliter | Geometric Coefficient of Variation 167.92 |
| Daprodustat 16 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 11.5783 Nanograms per milliliter | Geometric Coefficient of Variation 130.74 |
| Daprodustat 16 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=7, 19, 51, 59, 45, 28, 16, 3, 3 | 8.4814 Nanograms per milliliter | Geometric Coefficient of Variation 93.83 |
| Daprodustat 16 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=8, 20, 49, 57, 45, 28, 16, 3, 3 | 126.6824 Nanograms per milliliter | Geometric Coefficient of Variation 288.5 |
| Daprodustat 16 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 3.2007 Nanograms per milliliter | Geometric Coefficient of Variation 89.86 |
| Daprodustat 16 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=7, 18, 47, 56, 45, 28, 16, 3, 3 | 6.4276 Nanograms per milliliter | Geometric Coefficient of Variation 278.04 |
| Daprodustat 16 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=8, 17, 46, 59, 45, 27, 16, 3, 3 | 4.0850 Nanograms per milliliter | Geometric Coefficient of Variation 209.29 |
| Daprodustat 20 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=7, 18, 47, 56, 45, 28, 16, 3, 3 | 9.6617 Nanograms per milliliter | Geometric Coefficient of Variation 207.18 |
| Daprodustat 20 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 3.5712 Nanograms per milliliter | Geometric Coefficient of Variation 96.48 |
| Daprodustat 20 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=8, 19, 50, 59, 45, 28, 16, 3, 3 | 11.8995 Nanograms per milliliter | Geometric Coefficient of Variation 172.35 |
| Daprodustat 20 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 13.8509 Nanograms per milliliter | Geometric Coefficient of Variation 125.27 |
| Daprodustat 20 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=8, 17, 46, 59, 45, 27, 16, 3, 3 | 6.1029 Nanograms per milliliter | Geometric Coefficient of Variation 137.4 |
| Daprodustat 20 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=8, 20, 49, 57, 45, 28, 16, 3, 3 | 212.5087 Nanograms per milliliter | Geometric Coefficient of Variation 152.47 |
| Daprodustat 20 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=7, 19, 51, 59, 45, 28, 16, 3, 3 | 10.7368 Nanograms per milliliter | Geometric Coefficient of Variation 90.83 |
| Daprodustat 24 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 6.4555 Nanograms per milliliter | Geometric Coefficient of Variation 59.57 |
| Daprodustat 24 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=7, 18, 47, 56, 45, 28, 16, 3, 3 | 19.9693 Nanograms per milliliter | Geometric Coefficient of Variation 94.09 |
| Daprodustat 24 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=8, 17, 46, 59, 45, 27, 16, 3, 3 | 10.7532 Nanograms per milliliter | Geometric Coefficient of Variation 98.46 |
| Daprodustat 24 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 24.4926 Nanograms per milliliter | Geometric Coefficient of Variation 84.96 |
| Daprodustat 24 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=8, 20, 49, 57, 45, 28, 16, 3, 3 | 290.3163 Nanograms per milliliter | Geometric Coefficient of Variation 87.39 |
| Daprodustat 24 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=8, 19, 50, 59, 45, 28, 16, 3, 3 | 22.3378 Nanograms per milliliter | Geometric Coefficient of Variation 95.6 |
| Daprodustat 24 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=7, 19, 51, 59, 45, 28, 16, 3, 3 | 14.7926 Nanograms per milliliter | Geometric Coefficient of Variation 59.24 |
| Daprodustat 32 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=8, 17, 46, 59, 45, 27, 16, 3, 3 | 4.6296 Nanograms per milliliter | Geometric Coefficient of Variation 72 |
| Daprodustat 32 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 9.5457 Nanograms per milliliter | Geometric Coefficient of Variation 73.58 |
| Daprodustat 32 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 2.4981 Nanograms per milliliter | Geometric Coefficient of Variation 71.38 |
| Daprodustat 32 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=8, 20, 49, 57, 45, 28, 16, 3, 3 | 197.7071 Nanograms per milliliter | Geometric Coefficient of Variation 36.53 |
| Daprodustat 32 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=7, 19, 51, 59, 45, 28, 16, 3, 3 | 7.1458 Nanograms per milliliter | Geometric Coefficient of Variation 174.98 |
| Daprodustat 32 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=7, 18, 47, 56, 45, 28, 16, 3, 3 | 8.4327 Nanograms per milliliter | Geometric Coefficient of Variation 64.98 |
| Daprodustat 32 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=8, 19, 50, 59, 45, 28, 16, 3, 3 | 9.3582 Nanograms per milliliter | Geometric Coefficient of Variation 71.78 |
| Daprodustat 48 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=8, 20, 49, 57, 45, 28, 16, 3, 3 | 310.1938 Nanograms per milliliter | Geometric Coefficient of Variation 190.69 |
| Daprodustat 48 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=7, 19, 51, 59, 45, 28, 16, 3, 3 | 20.1044 Nanograms per milliliter | Geometric Coefficient of Variation 67.56 |
| Daprodustat 48 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=7, 18, 47, 56, 45, 28, 16, 3, 3 | 29.3042 Nanograms per milliliter | Geometric Coefficient of Variation 72.06 |
| Daprodustat 48 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 30.4034 Nanograms per milliliter | Geometric Coefficient of Variation 79.13 |
| Daprodustat 48 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=8, 19, 50, 59, 45, 28, 16, 3, 3 | 31.6698 Nanograms per milliliter | Geometric Coefficient of Variation 84.08 |
| Daprodustat 48 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=8, 17, 46, 59, 45, 27, 16, 3, 3 | 14.7844 Nanograms per milliliter | Geometric Coefficient of Variation 81.18 |
| Daprodustat 48 mg | Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=8, 19, 51, 59, 45, 28, 16, 3, 3 | 7.1245 Nanograms per milliliter | Geometric Coefficient of Variation 87.62 |
Secondary
Mean Average Monthly On-treatment Intravenous (IV) Iron Dose Per Participant
Average monthly IV iron dose (mg) per participant during Day 1 to Week 52 was determined by calculating the total IV iron dose per participant from Day 1 to Week 52 while the participant was on study treatment and dividing by (the number of days the participant was on study treatment divided by 30.4375 days). Analysis was performed using the ANCOVA model with terms for treatment, Baseline monthly IV iron dose, and region.
Time frame: Day 1 to Week 52
Population: All Randomized (ITT) Population. Only those participants with data available at specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Daprodustat | Mean Average Monthly On-treatment Intravenous (IV) Iron Dose Per Participant | 98.11 Milligrams | Standard Error 11.049 |
| Epoetin Alfa | Mean Average Monthly On-treatment Intravenous (IV) Iron Dose Per Participant | 106.23 Milligrams | Standard Error 15.569 |
p-value: 0.335495% CI: [-45.66, 29.41]ANCOVA
Secondary
Number of Hemoglobin Responders in the Hemoglobin Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52)
Mean hemoglobin during the evaluation period was defined as the mean of all evaluable hemoglobin values during the evaluation period (Week 28 to Week 52) including any evaluable unscheduled hemoglobin values that were taken during this time period. Hemoglobin responders were defined as the number of participants with a mean hemoglobin during the evaluation period that falls within the hemoglobin analysis range of 10-11.5 grams/deciliter.
Time frame: Week 28 to Week 52
Population: All Randomized (ITT) Population. Only those participants with at least one evaluable hemoglobin value during the evaluation period were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daprodustat | Number of Hemoglobin Responders in the Hemoglobin Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52) | 172 Participants |
| Epoetin Alfa | Number of Hemoglobin Responders in the Hemoglobin Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52) | 68 Participants |
p-value: 0.000795% CI: [0.06, 0.27]Cochran-Mantel-Haenszel
Secondary
Number of Participants With at Least One BP Exacerbation Event During the Study
BP exacerbation (based on post-dialysis BP) is defined as: SBP \>= 25 mmHg increased from Baseline or SBP \>=180mmHg; or DBP \>=15 mmHg increase from Baseline or DBP \>=110 mmHg. Number of participants with at least 1 BP exacerbation event have been reported.
Time frame: Up to 52 weeks
Population: All Randomized (ITT) Population. Only those participants with data available at specified time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daprodustat | Number of Participants With at Least One BP Exacerbation Event During the Study | 151 Participants |
| Epoetin Alfa | Number of Participants With at Least One BP Exacerbation Event During the Study | 91 Participants |
Secondary
Percentage of Participants Permanently Stopping Study Treatment Due to Meeting Rescue Criteria
Percentage of participants permanently stopping study treatment due to meeting rescue criteria has been presented.
Time frame: Up to Week 52
Population: All Randomized (ITT) Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Percentage of Participants Permanently Stopping Study Treatment Due to Meeting Rescue Criteria | 2.2 Percentage of participants |
| Epoetin Alfa | Percentage of Participants Permanently Stopping Study Treatment Due to Meeting Rescue Criteria | 2.2 Percentage of participants |
p-value: 0.530895% CI: [0.26, 4.22]Wald test
Secondary
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52)
Participants received treatment during the study to achieve or maintain hemoglobin level in the target range. Percentage of time for which hemoglobin level was maintained within the analysis range (10 to 11.5 grams/deciliter) has been presented.
Time frame: Week 28 to Week 52
Population: All Randomized (ITT) Population. Only those participants with at least one evaluable hemoglobin value during the evaluation period were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daprodustat | Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52) | 70.83 Percentage of days |
| Epoetin Alfa | Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52) | 61.76 Percentage of days |
p-value: 0.003495% CI: [2.83, 19.56]Van Elteren's test
Secondary
Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13)
Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat (GSK1278863) and its metabolites: GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13).
Time frame: Pre-dose on Day 1; Pre-dose and at 0.5, 1, 2, 3 hours post-dose on any one post-Baseline visit day between Week 8 and Week 52
Population: Pharmacokinetic Population comprised of all randomized participants for whom a post-Baseline pharmacokinetic sample was obtained and analyzed. Only those participants with data available at specified time points were analyzed (represented as n=X in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=6, 17, 45, 59, 43, 27, 16, 3, 3 | 0.9750 Nanograms per milliliter | Geometric Coefficient of Variation 408.49 |
| Daprodustat | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=6, 17, 45, 59, 44, 27, 16, 3, 3 | 1.4466 Nanograms per milliliter | Geometric Coefficient of Variation 190.8 |
| Daprodustat | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=4, 17,42, 57, 40, 25, 16, 3, 3 | 0.8623 Nanograms per milliliter | Geometric Coefficient of Variation 241.17 |
| Daprodustat | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=1, 2, 10, 18, 14, 9, 6, 3, 2 | 6.2400 Nanograms per milliliter | — |
| Daprodustat | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=4, 17, 45, 59, 43, 27, 16, 3, 3 | 0.9951 Nanograms per milliliter | Geometric Coefficient of Variation 122.94 |
| Daprodustat | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=1, 4, 5, 20, 14, 7, 4, 3, 2 | 0.3620 Nanograms per milliliter | — |
| Daprodustat | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=2, 7, 22, 41, 33, 20, 15, 3, 3 | 1.1778 Nanograms per milliliter | Geometric Coefficient of Variation 20.55 |
| Epoetin Alfa | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=4, 17, 45, 59, 43, 27, 16, 3, 3 | 0.8372 Nanograms per milliliter | Geometric Coefficient of Variation 121.27 |
| Epoetin Alfa | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=1, 2, 10, 18, 14, 9, 6, 3, 2 | 1.1207 Nanograms per milliliter | Geometric Coefficient of Variation 494.71 |
| Epoetin Alfa | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=6, 17, 45, 59, 44, 27, 16, 3, 3 | 3.5579 Nanograms per milliliter | Geometric Coefficient of Variation 102.68 |
| Epoetin Alfa | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=4, 17,42, 57, 40, 25, 16, 3, 3 | 0.5893 Nanograms per milliliter | Geometric Coefficient of Variation 255.59 |
| Epoetin Alfa | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=2, 7, 22, 41, 33, 20, 15, 3, 3 | 0.6069 Nanograms per milliliter | Geometric Coefficient of Variation 271.48 |
| Epoetin Alfa | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=1, 4, 5, 20, 14, 7, 4, 3, 2 | 0.2867 Nanograms per milliliter | Geometric Coefficient of Variation 111.67 |
| Epoetin Alfa | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=6, 17, 45, 59, 43, 27, 16, 3, 3 | 1.9588 Nanograms per milliliter | Geometric Coefficient of Variation 163.27 |
| Daprodustat 8 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=6, 17, 45, 59, 44, 27, 16, 3, 3 | 4.0910 Nanograms per milliliter | Geometric Coefficient of Variation 148.03 |
| Daprodustat 8 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=2, 7, 22, 41, 33, 20, 15, 3, 3 | 0.2362 Nanograms per milliliter | Geometric Coefficient of Variation 76.76 |
| Daprodustat 8 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=4, 17, 45, 59, 43, 27, 16, 3, 3 | 0.9634 Nanograms per milliliter | Geometric Coefficient of Variation 95.99 |
| Daprodustat 8 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=6, 17, 45, 59, 43, 27, 16, 3, 3 | 2.0381 Nanograms per milliliter | Geometric Coefficient of Variation 124.74 |
| Daprodustat 8 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=4, 17,42, 57, 40, 25, 16, 3, 3 | 0.6341 Nanograms per milliliter | Geometric Coefficient of Variation 123.92 |
| Daprodustat 8 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=1, 4, 5, 20, 14, 7, 4, 3, 2 | 0.1594 Nanograms per milliliter | Geometric Coefficient of Variation 16.91 |
| Daprodustat 8 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=1, 2, 10, 18, 14, 9, 6, 3, 2 | 0.1786 Nanograms per milliliter | Geometric Coefficient of Variation 77.35 |
| Daprodustat 12 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=1, 4, 5, 20, 14, 7, 4, 3, 2 | 0.2996 Nanograms per milliliter | Geometric Coefficient of Variation 105.55 |
| Daprodustat 12 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=6, 17, 45, 59, 44, 27, 16, 3, 3 | 6.8137 Nanograms per milliliter | Geometric Coefficient of Variation 102.34 |
| Daprodustat 12 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=4, 17, 45, 59, 43, 27, 16, 3, 3 | 1.5100 Nanograms per milliliter | Geometric Coefficient of Variation 105.5 |
| Daprodustat 12 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=2, 7, 22, 41, 33, 20, 15, 3, 3 | 0.4444 Nanograms per milliliter | Geometric Coefficient of Variation 144.99 |
| Daprodustat 12 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=1, 2, 10, 18, 14, 9, 6, 3, 2 | 0.3727 Nanograms per milliliter | Geometric Coefficient of Variation 277.88 |
| Daprodustat 12 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=6, 17, 45, 59, 43, 27, 16, 3, 3 | 3.5141 Nanograms per milliliter | Geometric Coefficient of Variation 136.72 |
| Daprodustat 12 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=4, 17,42, 57, 40, 25, 16, 3, 3 | 1.1572 Nanograms per milliliter | Geometric Coefficient of Variation 184.51 |
| Daprodustat 16 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=4, 17, 45, 59, 43, 27, 16, 3, 3 | 1.5480 Nanograms per milliliter | Geometric Coefficient of Variation 122.95 |
| Daprodustat 16 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=1, 2, 10, 18, 14, 9, 6, 3, 2 | 0.3443 Nanograms per milliliter | Geometric Coefficient of Variation 100.78 |
| Daprodustat 16 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=4, 17,42, 57, 40, 25, 16, 3, 3 | 1.1654 Nanograms per milliliter | Geometric Coefficient of Variation 191.57 |
| Daprodustat 16 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=1, 4, 5, 20, 14, 7, 4, 3, 2 | 0.3027 Nanograms per milliliter | Geometric Coefficient of Variation 69.12 |
| Daprodustat 16 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=6, 17, 45, 59, 43, 27, 16, 3, 3 | 3.3872 Nanograms per milliliter | Geometric Coefficient of Variation 182.27 |
| Daprodustat 16 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=2, 7, 22, 41, 33, 20, 15, 3, 3 | 0.3917 Nanograms per milliliter | Geometric Coefficient of Variation 169.77 |
| Daprodustat 16 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=6, 17, 45, 59, 44, 27, 16, 3, 3 | 5.6037 Nanograms per milliliter | Geometric Coefficient of Variation 130.97 |
| Daprodustat 20 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=1, 4, 5, 20, 14, 7, 4, 3, 2 | 0.2868 Nanograms per milliliter | Geometric Coefficient of Variation 109.23 |
| Daprodustat 20 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=2, 7, 22, 41, 33, 20, 15, 3, 3 | 0.3728 Nanograms per milliliter | Geometric Coefficient of Variation 197.51 |
| Daprodustat 20 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=1, 2, 10, 18, 14, 9, 6, 3, 2 | 0.3871 Nanograms per milliliter | Geometric Coefficient of Variation 161.05 |
| Daprodustat 20 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=6, 17, 45, 59, 43, 27, 16, 3, 3 | 3.6000 Nanograms per milliliter | Geometric Coefficient of Variation 173.62 |
| Daprodustat 20 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=4, 17, 45, 59, 43, 27, 16, 3, 3 | 1.6555 Nanograms per milliliter | Geometric Coefficient of Variation 133.94 |
| Daprodustat 20 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=6, 17, 45, 59, 44, 27, 16, 3, 3 | 8.4611 Nanograms per milliliter | Geometric Coefficient of Variation 128.74 |
| Daprodustat 20 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=4, 17,42, 57, 40, 25, 16, 3, 3 | 1.1792 Nanograms per milliliter | Geometric Coefficient of Variation 168.59 |
| Daprodustat 24 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=6, 17, 45, 59, 43, 27, 16, 3, 3 | 6.5730 Nanograms per milliliter | Geometric Coefficient of Variation 99.82 |
| Daprodustat 24 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=4, 17, 45, 59, 43, 27, 16, 3, 3 | 3.2099 Nanograms per milliliter | Geometric Coefficient of Variation 67.36 |
| Daprodustat 24 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=2, 7, 22, 41, 33, 20, 15, 3, 3 | 0.3992 Nanograms per milliliter | Geometric Coefficient of Variation 153.15 |
| Daprodustat 24 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=6, 17, 45, 59, 44, 27, 16, 3, 3 | 11.7372 Nanograms per milliliter | Geometric Coefficient of Variation 65.37 |
| Daprodustat 24 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=1, 4, 5, 20, 14, 7, 4, 3, 2 | 0.2585 Nanograms per milliliter | Geometric Coefficient of Variation 30.72 |
| Daprodustat 24 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=1, 2, 10, 18, 14, 9, 6, 3, 2 | 0.1621 Nanograms per milliliter | Geometric Coefficient of Variation 42.17 |
| Daprodustat 24 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=4, 17,42, 57, 40, 25, 16, 3, 3 | 1.4987 Nanograms per milliliter | Geometric Coefficient of Variation 136.35 |
| Daprodustat 32 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=4, 17, 45, 59, 43, 27, 16, 3, 3 | 1.6892 Nanograms per milliliter | Geometric Coefficient of Variation 30.44 |
| Daprodustat 32 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=1, 4, 5, 20, 14, 7, 4, 3, 2 | 0.2414 Nanograms per milliliter | Geometric Coefficient of Variation 29.66 |
| Daprodustat 32 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=6, 17, 45, 59, 43, 27, 16, 3, 3 | 4.2068 Nanograms per milliliter | Geometric Coefficient of Variation 15.44 |
| Daprodustat 32 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=4, 17,42, 57, 40, 25, 16, 3, 3 | 1.6974 Nanograms per milliliter | Geometric Coefficient of Variation 6.82 |
| Daprodustat 32 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=6, 17, 45, 59, 44, 27, 16, 3, 3 | 6.0453 Nanograms per milliliter | Geometric Coefficient of Variation 140.63 |
| Daprodustat 32 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=2, 7, 22, 41, 33, 20, 15, 3, 3 | 0.3963 Nanograms per milliliter | Geometric Coefficient of Variation 16.52 |
| Daprodustat 32 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=1, 2, 10, 18, 14, 9, 6, 3, 2 | 0.2768 Nanograms per milliliter | Geometric Coefficient of Variation 140.82 |
| Daprodustat 48 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | Daprodustat; n=1, 2, 10, 18, 14, 9, 6, 3, 2 | 0.3486 Nanograms per milliliter | Geometric Coefficient of Variation 68.34 |
| Daprodustat 48 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531398; n=2, 7, 22, 41, 33, 20, 15, 3, 3 | 0.2280 Nanograms per milliliter | Geometric Coefficient of Variation 56.68 |
| Daprodustat 48 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2531401; n=6, 17, 45, 59, 44, 27, 16, 3, 3 | 16.2584 Nanograms per milliliter | Geometric Coefficient of Variation 41.06 |
| Daprodustat 48 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2391220; n=4, 17,42, 57, 40, 25, 16, 3, 3 | 1.3531 Nanograms per milliliter | Geometric Coefficient of Variation 19.28 |
| Daprodustat 48 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506104; n=6, 17, 45, 59, 43, 27, 16, 3, 3 | 4.1894 Nanograms per milliliter | Geometric Coefficient of Variation 23.78 |
| Daprodustat 48 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2487818; n=1, 4, 5, 20, 14, 7, 4, 3, 2 | 0.2111 Nanograms per milliliter | Geometric Coefficient of Variation 80.56 |
| Daprodustat 48 mg | Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13) | GSK2506102; n=4, 17, 45, 59, 43, 27, 16, 3, 3 | 1.8595 Nanograms per milliliter | Geometric Coefficient of Variation 48.36 |