Anaemia
Conditions
Keywords
Safety, Efficacy, Daprodustat, Chronic kidney disease
Brief summary
Daprodustat is a drug that is currently being developed as a treatment for renal anemia . This study is to evaluate the efficacy and safety of daprodustat following a switch from erythropoiesis-stimulating agent (ESA) in Japanese HD subjects with renal anemia who are currently treated with ESA. The primary objective is to demonstrate non-inferiority of daprodustat to darbepoetin alfa. This study is a 52-week, Phase III, double-blind, active-controlled, parallel-group, multi-center study. The total duration of the study will be approximately 58 weeks including screening and follow-up.
Interventions
DRUGDaprodustat small
Available as 7.0 millimeter (mm) round, standard biconvex, white film coated tablets containing 1 mg, 2 mg, or 4 mg of daprodustat as active ingredient
DRUGDaprodustat small placebo
Available as 7.0 mm round, standard biconvex, white film coated tablets containing no daprodustat
DRUGDaprodustat large
Available as 9.0 mm round, standard biconvex, white film coated tablets containing 6 mg of daprodustat as active ingredient
DRUGDaprodustat large placebo
Available as 9.0 mm round, standard biconvex, white film coated tablets containing no daprodustat
DRUGDarbepoetin alfa
Available as 0.5 mL plastic prefilled syringes (PFS) for IV injection each containing 10, 15, 20, 30, 40 or 60 mcg of darbepoetin alfa in a clear and colorless solution.
DRUGDarbepoetin alfa placebo
Available as 0.5 mL plastic PFS for IV injection containing no darbepoetin alfa in a clear and colorless solution.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age (informed consent): \>=20 years of age * Dialysis: On HD or hemodiafiltration (HDF) given three times weekly for at least 12 weeks prior to screening * ESAs: Use of one and the same ESA for 10 weeks prior to screening * ESA dose: Darbepoetin alfa 10 to 60 μg per week, epoetin (including biosimilars) \<=9000 international units (IU) per week, or epoetin beta pegol \<=250 μg per 4 weeks * Hgb:\>=9.5 g/dL and \<=12.5 g/dL. Determined at the site using an Hgb analyzer * Iron parameters: Ferritin \>100 nanogram (ng)/millilitre (mL) or transferrin saturation (TSAT) \>20 percent (screening verification only) * Gender (screening verification only): Female or male Females: Not pregnant \[demonstrated to be negative for human chorionic gonadotropin (hCG) in serum\], not breast-feeding, and meet at least one of the following: • Females of non-childbearing potential are defined as follows: Pre-menopausal with at least one of the following and no plans to utilise assisted reproductive techniques (e.g., in vitro fertilisation or donor embryo transfer): * History of bilateral tubal ligation or salpingectomy * History of hysteroscopic tubal occlusion and postoperatively documented bilateral tubal obstruction * History of hysterectomy * History of bilateral oophorectomy Postmenopausal defined as A) females 60 years of age or older or B) In females \< 60 years of age, 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with postmenopausal follicle stimulating hormone (FSH) and estradiol concentrations is confirmatory (see separately specified reference ranges)\]. Females on hormone replacement therapy (HRT) whose menopausal status is in doubt will be required to use one of the most effective contraception methods if they wish to continue their HRT during the study. Otherwise they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. • Females of childbearing potential must agree to comply with one of the contraception methods listed as requirements in GlaxoSmithKline (GSK) Listing of Most Effective Contraceptive Methods for Females of Childbearing Potential from 28 days prior to the first dose of study medication until the completion of the follow-up visit. * Informed consent: Written informed consent, including adherence to the requirements and conditions specified in the consent form and the protocol, must be obtained from each subject.
Exclusion criteria
CKD-related criteria * Kidney transplant: Planned living-related kidney transplant during the study Anemia-related criteria * Aplasia: History of bone-marrow hypoplasia or pure red cell aplasia * Other causes of anemia: pernicious anemia, thalassemia, sickle cell anemia, or myelodysplastic syndromes * Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding within 10 weeks prior to screening or during a period from screening to Day 1 Cardiovascular disease-related criteria * Myocardial infarction, acute coronary syndrome, stroke, or transient ischemic attack: Diagnosed within 10 weeks prior to screening or during a period from screening to Day 1 * Heart failure: Chronic Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system * Corrected QT (QTc) Interval (screening verification only): QTc \>500 milliseconds (msec); or QTc \>530 msec in subjects with bundle branch block Note: QT interval corrected using the Bazett's formula (QTcB) will be used, and electrocardiogram (ECG) can be mechanically or manually read Other disease-related criteria: * Liver disease (if any of the following occurs): * Alanine transaminase (ALT) \>2 upper limit of normal (ULN) * Bilirubin \>1.5×ULN (isolated bilirubin \>1.5 ULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35 percent) * Current unstable active liver or biliary disease (generally defined by the onset of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, persistent jaundice, or cirrhosis) * Malignancy: History of malignancy within 2 years prior to screening, currently receiving treatment for cancer, or complex kidney cyst \>3 centimeters (cm) (II F, III or IV based on the Bosniak classification) Concomitant medication and other study treatment-related criteria * Iron: Planned use of intravenous iron during the screening phase or during a period from Day 1 to Week 4 * Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product. * Drugs and supplements: Use or planned use of any prescription or non-prescription drugs or dietary supplements that are prohibited during the study period \[prohibited medications: strong inducers and inhibitor of Cytochrome P450 (CYP) 2C8\]. * Prior investigational product exposure: Use of an investigational agent within 30 days or five half lives of the investigational agent (whichever is longer) * Prior treatment with daprodustat: Any prior treatment with daprodustat for a treatment duration of \>30 days General health-related criteria * Other conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator (or subinvestigator) considers would put the subject at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) | Weeks 40 to 52 | The mean hemoglobin during the Evaluation Period was estimated by a statistical model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hgb (Hgb Increase Rate) at Week 4 | Baseline and Week 4 | Change from Baseline was calculated as the post-dose Week 4 visit value minus the Baseline value. |
| Percentage of Participants by Hgb Change From Baseline Category at Week 4 | Week 4 | Percentage of participants within each category were provided only for daprodustat and the categories were classified into 6 (i.e., \<=-2, \>-2 to -1, \>-1 to 0, \>0 to 1, \>1 to 2, \>2 grams per deciliter \[g/dL\]). In addition, 'within 1.0 g/dL (i.e., \<=-1 and \>=1) and over 2.0 g/dL (i.e., \<-2 and \>2) categories were provided. |
| Distribution of Daprodustat Dose Level by Visit | Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44, and 48) | Distribution of dose level by visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for Daprodustat. Median along with the interquartile range (25th and 75th percentile) has been presented. |
| Distribution of Darbepoetin Alfa Dose Level by Visit | Day 1, Weeks 2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48, and 50 | Distribution of dose level by visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for Darbepoetin Alfa. Median along with the interquartile range (25th and 75th percentile) has been presented. |
| Duration of Treatment Interruption Due to Hgb >13 g/dL | Up to Week 52 | Duration of treatment interruption due to Hgb \>13 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for the daprodustat group. |
| Number of Dose Adjustments for Daprodustat | Up to Week 52 | Number of dose adjustments has been presented only for daprodustat. |
| Hgb Values at Each Assessment Visit | Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52 | Hgb values at each assessment visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented. |
| Change From Baseline in Hgb Values at Each Assessment Visit | Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52 | Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calcuated as the post-dose visit value minus the Baseline value. Change from Baseline Hgb values at each assessment visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented. |
| Percentage of Participants With Mean Hgb in the Target Range (10.0-12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) | Weeks 40 to 52 | The percentage of participants with observed mean Hgb within the target range during the primary efficacy evaluation period was summarized. Odds ratio was estimated using a logistic regression and provided along with its 95% CI and a one-sided p-value. |
| Percentage of Time in Hgb Target Range (10.0 to 12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) | Weeks 40 to 52 | Percentage of time in Hgb target range (10.0 to 12.0 g/dL) during the primary efficacy evaluation period (Weeks 40 to 52) for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented. |
| Number of Participants Who Had an Hgb Level of Less Than 7.5 g/dL | Up to Week 52 | If an initial Hgb value was less than 7.5 g/dL, measurement was repeated at the same study visit (using the same sample) to calculate the average. If the average met the Hgb stopping criteria, study treatment was permanently discontinued. Number of participants who had an Hgb level of less than 7.5 g/dL has been presented. |
| Number of Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks | Up to Week 52 | Number of participants who had an Hgb increase of more than 2 g/dL over any 4 weeks for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented. |
| Number of Participants Who Had an Hgb Level of More Than 13.0 g/dL | Up to Week 52 | Number of participants who had an Hgb increase of more than 13 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented. |
| Number of Episodes With Hgb Level of More Than 13.0 g/dL | Up to Week 52 | Number of episodes with Hgb level of more than 13.0 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented. |
| Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat | 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24 | Blood samples for Pharmacokinetic (PK) analysis of daprodustat were collected as the time points provided. PK parameters were calculated by standard non-compartmental analysis according to current working practices and using the currently supported version of WinNonlin (version 6.3 or higher). NA indicates geometric co-efficient of variation could not be calculated as a single participant was analyzed. Data has been provided as a consolidated values for at all time-points (0,1,2,3,and 4 hours post-dose) as provided for a single value at Weeks 12 and 24 respectively. PK population comprised of all daprodustat-treated participants from whom PK samples were collected and analyzed. Data was not calculated for darbepoetin alfa group as the primary interest of analysis was Daprodustat and not comparator drug (darbepoetin alfa). Data is combined from Week 12 and Week 24 data. |
| Maximum Concentration (Cmax) of Plasma Daprodustat | 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24 | Blood samples for PK analysis of daprodustat were collected as the time points provided. PK parameters were calculated by standard non-compartmental analysis according to current working practices and using the currently supported version of WinNonlin (version 6.3 or higher). Data has been provided as a consolidated values for at all time-points (0,1,2,3,and 4 hours post-dose) as provided for a single value at Weeks 12 and 24 respectively. Data was not calculated for darbepoetin alfa group as the primary interest of analysis was Daprodustat and not comparator drug (darbepoetin alfa). Data is combined from Week 12 and Week 24 data. |
| Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52 | Percentage of participants with Hgb within the target range was summarized at each assessment visit by treatment group have been presented. |
Countries
Japan
Participant flow
Recruitment details
A total of 50 centers, contracted in Japan, enrolled and randomized participants. A total of 271 participants were enrolled and randomized in this study.
Pre-assignment details
A total of 332 participants were screened of which 61 failed screening reasons being participants did not meet inclusion/exclusion criteria (48), physician decision (3) and withdrawn by participant (10), hence 271 participants were enrolled and randomized.
Participants by arm
| Arm | Count |
|---|---|
| Daprodustat Participants received oral daprodustat tablets (1, 2, 4, 6, 8, 12, 18 and 24 milligrams \[mg\] as recommended) once daily and intravenous (IV) darbepoetin alfa placebo injection (0.5 milliliter prefilled syringes containing no darbepoetin alfa) once weekly for 52 weeks. | 136 |
| Darbepoetin Alfa Participant received IV darbepoetin alfa injection (10,15,20,30,40 and 60 micrograms \[ug\] as recommended) once weekly and oral daprodustat placebo tablets (small and large tablets containing no daprodustat) once daily for 52 weeks. | 135 |
| Total | 271 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 8 |
| Overall Study | Physician Decision | 4 | 3 |
| Overall Study | Protocol-specified withdrawal criteria | 4 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Daprodustat | Darbepoetin Alfa | Total |
|---|---|---|---|
| Age, Continuous | 64.1 Years STANDARD_DEVIATION 10.3 | 63.5 Years STANDARD_DEVIATION 10.54 | 63.8 Years STANDARD_DEVIATION 10.4 |
| Race/Ethnicity, Customized Asian - Japanese heritage | 136 Count of participants | 135 Count of participants | 271 Count of participants |
| Sex: Female, Male Female | 45 Participants | 46 Participants | 91 Participants |
| Sex: Female, Male Male | 91 Participants | 89 Participants | 180 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 136 | 1 / 135 |
| other Total, other adverse events | 102 / 136 | 102 / 135 |
| serious Total, serious adverse events | 21 / 136 | 37 / 135 |
Outcome results
Primary
Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)
The mean hemoglobin during the Evaluation Period was estimated by a statistical model.
Time frame: Weeks 40 to 52
Population: Intent to treat (ITT) Population comprised of all randomized participants who had a Baseline and at least one post Baseline schedule Hgb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Daprodustat | Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) | 10.89 Grams per deciliter (g/dL) | Standard Error 0.062 |
| Darbepoetin Alfa | Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) | 10.83 Grams per deciliter (g/dL) | Standard Error 0.06 |
p-value: <0.000195% CI: [-0.11, 0.23]Mixed model repeated measures (MMRM)
Secondary
Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat
Blood samples for Pharmacokinetic (PK) analysis of daprodustat were collected as the time points provided. PK parameters were calculated by standard non-compartmental analysis according to current working practices and using the currently supported version of WinNonlin (version 6.3 or higher). NA indicates geometric co-efficient of variation could not be calculated as a single participant was analyzed. Data has been provided as a consolidated values for at all time-points (0,1,2,3,and 4 hours post-dose) as provided for a single value at Weeks 12 and 24 respectively. PK population comprised of all daprodustat-treated participants from whom PK samples were collected and analyzed. Data was not calculated for darbepoetin alfa group as the primary interest of analysis was Daprodustat and not comparator drug (darbepoetin alfa). Data is combined from Week 12 and Week 24 data.
Time frame: 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat | 1 mg, n=8 | 27.57 Hours*nanograms per milliliter | Geometric Coefficient of Variation 147.6 |
| Daprodustat | Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat | 2 mg, n=24 | 44.52 Hours*nanograms per milliliter | Geometric Coefficient of Variation 139.2 |
| Daprodustat | Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat | 4 mg, n=91 | 72.68 Hours*nanograms per milliliter | Geometric Coefficient of Variation 242.2 |
| Daprodustat | Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat | 6 mg, n=61 | 140.58 Hours*nanograms per milliliter | Geometric Coefficient of Variation 238.9 |
| Daprodustat | Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat | 8 mg, n=38 | 170.41 Hours*nanograms per milliliter | Geometric Coefficient of Variation 136.1 |
| Daprodustat | Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat | 12 mg, n=17 | 150.53 Hours*nanograms per milliliter | Geometric Coefficient of Variation 176.4 |
| Daprodustat | Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat | 18 mg, n=5 | 488.93 Hours*nanograms per milliliter | Geometric Coefficient of Variation 89.2 |
Secondary
Change From Baseline in Hgb (Hgb Increase Rate) at Week 4
Change from Baseline was calculated as the post-dose Week 4 visit value minus the Baseline value.
Time frame: Baseline and Week 4
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daprodustat | Change From Baseline in Hgb (Hgb Increase Rate) at Week 4 | -0.42 g/dL | Standard Deviation 0.898 |
| Darbepoetin Alfa | Change From Baseline in Hgb (Hgb Increase Rate) at Week 4 | 0.08 g/dL | Standard Deviation 0.525 |
Secondary
Change From Baseline in Hgb Values at Each Assessment Visit
Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calcuated as the post-dose visit value minus the Baseline value. Change from Baseline Hgb values at each assessment visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented.
Time frame: Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52
Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 8, n=127, 132 | -0.45 g/dL | Standard Deviation 1.178 |
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 32, n=122, 127 | 0.16 g/dL | Standard Deviation 1.119 |
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 16, n=124, 129 | -0.38 g/dL | Standard Deviation 1.348 |
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 36, n=121, 127 | 0.17 g/dL | Standard Deviation 1.02 |
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 4, n=133, 134 | -0.42 g/dL | Standard Deviation 0.898 |
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 40, n=120, 125 | 0.03 g/dL | Standard Deviation 1.06 |
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 20, n=123, 129 | -0.09 g/dL | Standard Deviation 1.161 |
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 44, n=117, 125 | 0.03 g/dL | Standard Deviation 1.118 |
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 12, n=125, 129 | -0.42 g/dL | Standard Deviation 1.258 |
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 48, n=117, 124 | -0.01 g/dL | Standard Deviation 1.164 |
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 24, n=123, 129 | 0.07 g/dL | Standard Deviation 1.106 |
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 52,n=115, 120 | -0.16 g/dL | Standard Deviation 1.169 |
| Daprodustat | Change From Baseline in Hgb Values at Each Assessment Visit | Week 28, n=123, 129 | 0.03 g/dL | Standard Deviation 1.084 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 52,n=115, 120 | 0.01 g/dL | Standard Deviation 1.019 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 4, n=133, 134 | 0.08 g/dL | Standard Deviation 0.525 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 8, n=127, 132 | 0.20 g/dL | Standard Deviation 0.821 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 12, n=125, 129 | 0.27 g/dL | Standard Deviation 1.021 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 16, n=124, 129 | 0.09 g/dL | Standard Deviation 1.146 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 20, n=123, 129 | 0.12 g/dL | Standard Deviation 1.12 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 28, n=123, 129 | 0.04 g/dL | Standard Deviation 1.08 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 32, n=122, 127 | 0.14 g/dL | Standard Deviation 1.071 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 36, n=121, 127 | 0.09 g/dL | Standard Deviation 1.041 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 40, n=120, 125 | 0.10 g/dL | Standard Deviation 1.034 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 44, n=117, 125 | 0.07 g/dL | Standard Deviation 1.019 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 48, n=117, 124 | -0.04 g/dL | Standard Deviation 0.978 |
| Darbepoetin Alfa | Change From Baseline in Hgb Values at Each Assessment Visit | Week 24, n=123, 129 | 0.10 g/dL | Standard Deviation 1.068 |
Secondary
Distribution of Daprodustat Dose Level by Visit
Distribution of dose level by visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for Daprodustat. Median along with the interquartile range (25th and 75th percentile) has been presented.
Time frame: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44, and 48)
Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Week 4, n=133 | 4.0 milligrams per day (mg/day) |
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Week 8, n=126 | 4.0 milligrams per day (mg/day) |
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Week 12, n=125 | 6.0 milligrams per day (mg/day) |
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Week 16, n=123 | 6.0 milligrams per day (mg/day) |
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Week 32, n=122 | 6.0 milligrams per day (mg/day) |
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Week 36, n=121 | 6.0 milligrams per day (mg/day) |
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Day 1, n=133 | 4.0 milligrams per day (mg/day) |
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Week 20, n=123 | 6.0 milligrams per day (mg/day) |
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Week 24, n=123 | 6.0 milligrams per day (mg/day) |
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Week 28, n=123 | 6.0 milligrams per day (mg/day) |
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Week 40, n=119 | 6.0 milligrams per day (mg/day) |
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Week 44, n=117 | 6.0 milligrams per day (mg/day) |
| Daprodustat | Distribution of Daprodustat Dose Level by Visit | Week 48, n=117 | 6.0 milligrams per day (mg/day) |
Secondary
Distribution of Darbepoetin Alfa Dose Level by Visit
Distribution of dose level by visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for Darbepoetin Alfa. Median along with the interquartile range (25th and 75th percentile) has been presented.
Time frame: Day 1, Weeks 2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48, and 50
Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 24, n=129 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 26, n=129 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 28, n=127 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 30, n=128 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 32, n=127 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Day 1, n=134 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 2. n=134 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 4, n=134 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 6, n=133 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 8, n=131 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 10, n=129 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 12, n=129 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 14, n=129 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 16, n=129 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 18, n=129 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 20, n=129 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 22, n=128 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 34, n=127 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 36, n=127 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 38, n=127 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 40, n=125 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 42, n=125 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 44, n=125 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 46, n=125 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 48, n=124 | 15.0 micrograms per week (ug/week) |
| Daprodustat | Distribution of Darbepoetin Alfa Dose Level by Visit | Week 50, n=122 | 15.0 micrograms per week (ug/week) |
Secondary
Duration of Treatment Interruption Due to Hgb >13 g/dL
Duration of treatment interruption due to Hgb \>13 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for the daprodustat group.
Time frame: Up to Week 52
Population: ITT Population. Only those participants with data available at the time of assessment were used for analysis. Summary data for Darbepoetin alfa group could not be collected as comparison was not reasonable because of the difference in dose adjustment frequency. Median along with inter quartile range (25th and 75th percentile) have been presented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daprodustat | Duration of Treatment Interruption Due to Hgb >13 g/dL | 28.0 Days |
Secondary
Hgb Values at Each Assessment Visit
Hgb values at each assessment visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented.
Time frame: Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52
Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Hgb Values at Each Assessment Visit | Week 4, n=133, 134 | 10.52 g/dL | Standard Deviation 0.984 |
| Daprodustat | Hgb Values at Each Assessment Visit | Week 24, n=123, 129 | 11.01 g/dL | Standard Deviation 0.718 |
| Daprodustat | Hgb Values at Each Assessment Visit | Week 32, n=122, 127 | 11.10 g/dL | Standard Deviation 0.829 |
| Daprodustat | Hgb Values at Each Assessment Visit | Week 28, n=123, 129 | 10.97 g/dL | Standard Deviation 0.748 |
| Daprodustat | Hgb Values at Each Assessment Visit | Week 20, n=123, 129 | 10.85 g/dL | Standard Deviation 0.784 |
| Daprodustat | Hgb Values at Each Assessment Visit | Week 36, n=121, 127 | 11.12 g/dL | Standard Deviation 0.827 |
| Daprodustat | Hgb Values at Each Assessment Visit | Baseline (Day 1), n=133, 134 | 10.94 g/dL | Standard Deviation 0.77 |
| Daprodustat | Hgb Values at Each Assessment Visit | Week 40, n=120, 125 | 10.97 g/dL | Standard Deviation 0.86 |
| Daprodustat | Hgb Values at Each Assessment Visit | Week 12, n=125, 129 | 10.53 g/dL | Standard Deviation 0.989 |
| Daprodustat | Hgb Values at Each Assessment Visit | Week 44, n=117, 125 | 10.98 g/dL | Standard Deviation 0.912 |
| Daprodustat | Hgb Values at Each Assessment Visit | Week 8, n=127, 132 | 10.50 g/dL | Standard Deviation 1.069 |
| Daprodustat | Hgb Values at Each Assessment Visit | Week 48, n=117, 124 | 10.94 g/dL | Standard Deviation 0.893 |
| Daprodustat | Hgb Values at Each Assessment Visit | Week 52,n=115, 120 | 10.79 g/dL | Standard Deviation 0.807 |
| Daprodustat | Hgb Values at Each Assessment Visit | Week 16, n=124, 129 | 10.57 g/dL | Standard Deviation 0.97 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 52,n=115, 120 | 10.79 g/dL | Standard Deviation 0.841 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 4, n=133, 134 | 10.90 g/dL | Standard Deviation 0.829 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 8, n=127, 132 | 11.01 g/dL | Standard Deviation 0.824 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 20, n=123, 129 | 10.95 g/dL | Standard Deviation 0.83 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 28, n=123, 129 | 10.86 g/dL | Standard Deviation 0.872 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 48, n=117, 124 | 10.76 g/dL | Standard Deviation 0.83 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 12, n=125, 129 | 11.09 g/dL | Standard Deviation 0.753 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 16, n=124, 129 | 10.92 g/dL | Standard Deviation 0.862 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 24, n=123, 129 | 10.92 g/dL | Standard Deviation 0.859 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 32, n=122, 127 | 10.96 g/dL | Standard Deviation 0.82 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 36, n=121, 127 | 10.91 g/dL | Standard Deviation 0.847 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 40, n=120, 125 | 10.90 g/dL | Standard Deviation 0.835 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Week 44, n=117, 125 | 10.87 g/dL | Standard Deviation 0.904 |
| Darbepoetin Alfa | Hgb Values at Each Assessment Visit | Baseline (Day 1), n=133, 134 | 10.82 g/dL | Standard Deviation 0.732 |
Secondary
Maximum Concentration (Cmax) of Plasma Daprodustat
Blood samples for PK analysis of daprodustat were collected as the time points provided. PK parameters were calculated by standard non-compartmental analysis according to current working practices and using the currently supported version of WinNonlin (version 6.3 or higher). Data has been provided as a consolidated values for at all time-points (0,1,2,3,and 4 hours post-dose) as provided for a single value at Weeks 12 and 24 respectively. Data was not calculated for darbepoetin alfa group as the primary interest of analysis was Daprodustat and not comparator drug (darbepoetin alfa). Data is combined from Week 12 and Week 24 data.
Time frame: 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Daprodustat | Maximum Concentration (Cmax) of Plasma Daprodustat | 1 mg, n=8 | 16.11 Nanograms per milliliter | Geometric Coefficient of Variation 105.7 |
| Daprodustat | Maximum Concentration (Cmax) of Plasma Daprodustat | 2 mg, n=24 | 25.16 Nanograms per milliliter | Geometric Coefficient of Variation 122.7 |
| Daprodustat | Maximum Concentration (Cmax) of Plasma Daprodustat | 4 mg, n=91 | 42.45 Nanograms per milliliter | Geometric Coefficient of Variation 237.9 |
| Daprodustat | Maximum Concentration (Cmax) of Plasma Daprodustat | 6 mg, n=61 | 83.60 Nanograms per milliliter | Geometric Coefficient of Variation 269.7 |
| Daprodustat | Maximum Concentration (Cmax) of Plasma Daprodustat | 8 mg, n=38 | 105.71 Nanograms per milliliter | Geometric Coefficient of Variation 110.9 |
| Daprodustat | Maximum Concentration (Cmax) of Plasma Daprodustat | 12 mg, n=17 | 108.58 Nanograms per milliliter | Geometric Coefficient of Variation 117.8 |
| Daprodustat | Maximum Concentration (Cmax) of Plasma Daprodustat | 18 mg, n=5 | 306.61 Nanograms per milliliter | Geometric Coefficient of Variation 61 |
Secondary
Number of Dose Adjustments for Daprodustat
Number of dose adjustments has been presented only for daprodustat.
Time frame: Up to Week 52
Population: ITT Population. Summary data for Darbepoetin alfa group could not be collected as comparison was not reasonable because of the difference in dose adjustment frequency.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daprodustat | Number of Dose Adjustments for Daprodustat | 2.0 Dose adjustments |
Secondary
Number of Episodes With Hgb Level of More Than 13.0 g/dL
Number of episodes with Hgb level of more than 13.0 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented.
Time frame: Up to Week 52
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Number of Episodes With Hgb Level of More Than 13.0 g/dL | 9 Episodes |
| Darbepoetin Alfa | Number of Episodes With Hgb Level of More Than 13.0 g/dL | 12 Episodes |
Secondary
Number of Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks
Number of participants who had an Hgb increase of more than 2 g/dL over any 4 weeks for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented.
Time frame: Up to Week 52
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daprodustat | Number of Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks | 1 Participants |
| Darbepoetin Alfa | Number of Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks | 2 Participants |
Secondary
Number of Participants Who Had an Hgb Level of Less Than 7.5 g/dL
If an initial Hgb value was less than 7.5 g/dL, measurement was repeated at the same study visit (using the same sample) to calculate the average. If the average met the Hgb stopping criteria, study treatment was permanently discontinued. Number of participants who had an Hgb level of less than 7.5 g/dL has been presented.
Time frame: Up to Week 52
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Number of Participants Who Had an Hgb Level of Less Than 7.5 g/dL | 0 Percentage of participants |
| Darbepoetin Alfa | Number of Participants Who Had an Hgb Level of Less Than 7.5 g/dL | 0 Percentage of participants |
Secondary
Number of Participants Who Had an Hgb Level of More Than 13.0 g/dL
Number of participants who had an Hgb increase of more than 13 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented.
Time frame: Up to Week 52
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daprodustat | Number of Participants Who Had an Hgb Level of More Than 13.0 g/dL | 7 Percentage of participants |
| Darbepoetin Alfa | Number of Participants Who Had an Hgb Level of More Than 13.0 g/dL | 8 Percentage of participants |
Secondary
Percentage of Participants by Hgb Change From Baseline Category at Week 4
Percentage of participants within each category were provided only for daprodustat and the categories were classified into 6 (i.e., \<=-2, \>-2 to -1, \>-1 to 0, \>0 to 1, \>1 to 2, \>2 grams per deciliter \[g/dL\]). In addition, 'within 1.0 g/dL (i.e., \<=-1 and \>=1) and over 2.0 g/dL (i.e., \<-2 and \>2) categories were provided.
Time frame: Week 4
Population: ITT Population. Data for Darbepoetin alfa group could not be collected as comparison was not reasonable because of the difference in dose adjustment frequency.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daprodustat | Percentage of Participants by Hgb Change From Baseline Category at Week 4 | > -1.0 and <= 0 | 44 Percentage of participants |
| Daprodustat | Percentage of Participants by Hgb Change From Baseline Category at Week 4 | > 0 and <= 1.0 | 27 Percentage of participants |
| Daprodustat | Percentage of Participants by Hgb Change From Baseline Category at Week 4 | <= -2.0 | 5 Percentage of participants |
| Daprodustat | Percentage of Participants by Hgb Change From Baseline Category at Week 4 | > -2.0 and <= -1.0 | 21 Percentage of participants |
| Daprodustat | Percentage of Participants by Hgb Change From Baseline Category at Week 4 | > 1.0 and <= 2.0 | 4 Percentage of participants |
| Daprodustat | Percentage of Participants by Hgb Change From Baseline Category at Week 4 | > 2.0 | 0 Percentage of participants |
| Daprodustat | Percentage of Participants by Hgb Change From Baseline Category at Week 4 | within +/- 1.0 | 75 Percentage of participants |
| Daprodustat | Percentage of Participants by Hgb Change From Baseline Category at Week 4 | over +/- 2.0 | 5 Percentage of participants |
Secondary
Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit
Percentage of participants with Hgb within the target range was summarized at each assessment visit by treatment group have been presented.
Time frame: Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52
Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Baseline (Day 1), n=133, 134 | 79 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 4, n=133,134 | 65 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 8, n=127,132 | 65 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 12, n=125,129 | 66 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 16, n=124,129 | 64 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 20, n=123,129 | 82 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 24, n=123,129 | 85 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 28, n=123,129 | 85 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 32, n=122, 127 | 79 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 36, n=121,127 | 78 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 40, n=120,125 | 77 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 44, n=117,125 | 74 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 48, n=117,124 | 77 Percentage of participants |
| Daprodustat | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 52, n=115,120 | 77 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 40, n=120,125 | 80 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Baseline (Day 1), n=133, 134 | 87 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 28, n=123,129 | 82 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 4, n=133,134 | 80 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 48, n=117,124 | 79 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 8, n=127,132 | 84 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 32, n=122, 127 | 80 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 12, n=125,129 | 86 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 44, n=117,125 | 82 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 16, n=124,129 | 80 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 36, n=121,127 | 78 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 20, n=123,129 | 81 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 52, n=115,120 | 80 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit | Week 24, n=123,129 | 81 Percentage of participants |
Secondary
Percentage of Participants With Mean Hgb in the Target Range (10.0-12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)
The percentage of participants with observed mean Hgb within the target range during the primary efficacy evaluation period was summarized. Odds ratio was estimated using a logistic regression and provided along with its 95% CI and a one-sided p-value.
Time frame: Weeks 40 to 52
Population: Modified Intent to treat (mITT) comprised of all ITT participants who had at least one Hgb measurement during the evaluation period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daprodustat | Percentage of Participants With Mean Hgb in the Target Range (10.0-12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) | Responder | 88 Percentage of participants |
| Daprodustat | Percentage of Participants With Mean Hgb in the Target Range (10.0-12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) | Non-responder | 13 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants With Mean Hgb in the Target Range (10.0-12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) | Responder | 90 Percentage of participants |
| Darbepoetin Alfa | Percentage of Participants With Mean Hgb in the Target Range (10.0-12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) | Non-responder | 10 Percentage of participants |
p-value: 0.744295% CI: [0.34, 1.71]Regression, Logistic
Secondary
Percentage of Time in Hgb Target Range (10.0 to 12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)
Percentage of time in Hgb target range (10.0 to 12.0 g/dL) during the primary efficacy evaluation period (Weeks 40 to 52) for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented.
Time frame: Weeks 40 to 52
Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daprodustat | Percentage of Time in Hgb Target Range (10.0 to 12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) | 76.81 Percentage of time | Standard Deviation 30.387 |
| Darbepoetin Alfa | Percentage of Time in Hgb Target Range (10.0 to 12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) | 80.23 Percentage of time | Standard Deviation 28.038 |