CClinicalTrials.gg
Sign In
CompletedNCT03409107Updated Apr 2, 2024Results posted

Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat in Non-Dialysis Subjects Evaluating Hemoglobin (Hgb) and Quality of Life (ASCEND-NHQ)

A Phase 3 interventional study of Daprodustat (GSK1278863) and Placebo in Anaemia, sponsored by GlaxoSmithKline. Completed at 168 sites in 14 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-04-02.

Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
614
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this multi-center study in non-dialysis participants with anemia associated with CKD is to evaluate safety, efficacy and quality of life of daprodustat compared to placebo.

02

Conditions studied

  • Anaemia

Keywords

  • Non-Dialysis
  • Anemia
  • Chronic kidney disease
  • Recombinant human erythropoietin naïve
  • Hemoglobin
  • Daprodustat
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • >=18 years of age at the time of signing the informed consent.
  • Have CKD, confirmed at screening: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by Estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
  • Participants with Stable HemoCue Hgb from 8.5 to 10.5 at screening visit (Week -4) and from 8.5 to 10.0 g/dL at randomization (Day 1).
  • Participants may receive up to one intravenous (IV) iron dose within the 8 weeks prior to screening and NO IV iron use between screening visit and randomization (Day 1).
  • If needed, participant may be on stable maintenance oral iron supplementation. There should be \<50% change in overall dose and no change in type of iron prescribed in the 4 weeks prior to Day 1 randomization visit.
  • Male and female participants are eligible. A female participant 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 WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 weeks after the last dose of study treatment.
  • Capable of giving signed informed consent.

Exclusion criteria

Exclusion Criteria:

  • Participants who are on dialysis or clinical evidence of impending need to initiate dialysis within 180 days after randomization (Day 1).
  • Planned living-related or living-unrelated kidney transplant within 28 weeks after randomization (Day 1).
  • Transferrin saturation (TSAT) \<15 percent (Screening only).
  • Ferritin \<50 nanograms per milliliter (ng/mL) (Screening only).
  • History of rhEPO or rhEPO analogue use within the 8 weeks prior to screening and rhEPO use between screening and randomization (Day 1).
  • History of transfusion within the 8 weeks prior to screening and transfusion between screening and randomization (Day 1).
  • History of bone marrow aplasia or pure red cell aplasia (PRCA).
  • Participants with Megaloblastic anemia (untreated pernicious anemia and folate deficiency), thalassemia major, sickle cell disease or myelodysplastic syndrome.
  • Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal (GI) bleeding \<= 8 weeks prior to screening through to randomization (Day 1).
  • History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
  • Use of strong inhibitor of CYP2C8 (for example, gemfibrozil) or strong inducers of CYP2C8 (for example, rifampin/rifampicin).
  • Ferric citrate use within 4 weeks prior to randomization (Day 1).
  • Use of other investigational agent or device prior to screening through to randomization (Day 1).
  • Any prior treatment with daprodustat for a treatment duration of >30 days.
  • MI or acute coronary syndrome within the 8 weeks prior to screening through to randomization. (Day 1).
  • Stroke or transient ischemic attack within the 8 weeks prior to screening through to randomization. (Day 1).
  • Chronic Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
  • QT interval corrected by Bazett's formula (QTcB) >500 milliseconds (msec) or QTcB >530 msec in participants with bundle branch block. There is no corrected QT interval (QTc) exclusion for participants with a predominantly paced rhythm.
  • Alanine transaminase (ALT) >2x upper limit of normal (ULN) at screening (Week -4).
  • Bilirubin >1.5xULN at screening (Week -4).
  • 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.
  • History of malignancy within the 2 years prior to screening through to randomization (Day 1), or currently receiving treatment for cancer, or complex kidney cyst (for example, Bosniak Category II F, III or IV) > 3 centimeters (cm).
  • Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
  • Current uncontrolled hypertension as determined by the investigator.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
614 participants (actual)

Study arms

  • Experimental
    Daprodustat receivers

    Participants will receive oral daprodustat once daily

    Drug: Daprodustat (GSK1278863) · Drug: Iron therapy

  • Placebo comparator
    Placebo receivers

    Participants will receive oral placebo once daily

    Drug: Placebo · Drug: Iron therapy

Interventions

  • DrugDaprodustat (GSK1278863)

    Daprodustat will be available as 9 millimeter (mm) or 7 mm film-coated tablets. Daprodustat will be administered once daily via oral route and can be taken without regard to food.

  • DrugPlacebo

    Daprodustat matching placebo will be available as 9 mm or 7 mm film coated tablets. Placebo will be administered once daily via oral route and can be taken without regard to food.

  • DrugIron therapy

    Iron therapy will be administered if ferritin is \<50 Nano gram per milliliter and/or TSAT is \<15 percent.

05

What researchers measure

Primary outcomes

  1. Mean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28)

    Blood samples were collected at given time points from participants for hemoglobin measurements. Evaluation period hemoglobin value was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 24 to Week 28 inclusive). For the primary analysis, the missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputations. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using the Analysis of Covariance (ANCOVA) model with terms for treatment, Baseline hemoglobin, and region.

    Time frame: Baseline (Day 1) and Week 24 to Week 28

Secondary outcomes

  1. Percentage of Participants With Hemoglobin Increase of >=1.0 Grams Per Deciliter From Baseline to Evaluation Period

    Blood samples were collected at given time points for hemoglobin measurements. Evaluation period hemoglobin value was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 24 to Week 28 inclusive). For the primary analysis, the missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputations. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date. Percentage of participants with hemoglobin increase of \>=1.0 grams per deciliter from Baseline to evaluation period was analyzed using Cochran-Mantel-Haenszel (CMH) chi-squared test. The percentage values presented has been rounded off.

    Time frame: Baseline (Day 1) and Week 24 to Week 28

  2. Change From Baseline in Short Form-36 (SF-36) Questionnaire Vitality Domain Score by Traditional Scoring at Week 28

    The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the 8 health domains: Physical Functioning, Role-Physical (role limitations caused by physical problems), Social Functioning, Bodily Pain, Mental Health, Role-Emotional (role limitations caused by emotional problems), Vitality, and General Perception of Health.Each domain is scored from 0 (poorer health) to 100 (better health). Vitality domain score ranges from 0-100; higher score indicates a better health state \& better functioning. Change from Baseline was calculated as Post-Dose Visit Value at Week 28 minus Baseline. For primary analysis, the missing on-treatment Week 28 SF-36 Vitality domain scores were imputed using pre-specified multiple imputations. Baseline value was latest non-missing pre-dose assessment on or before randomization date. Analysis was performed using ANCOVA model with terms for treatment, Baseline score, and region.

    Time frame: Baseline (Day 1) and Week 28

  3. Percentage of Participants With Hgb Response (Hgb in the 11-12 Grams/Deciliter Range) During Evaluation Period (Week 24 to Week 28 Inclusive)

    Mean hemoglobin during the evaluation period was defined as the mean of all evaluable hemoglobin values during the evaluation period (Week 24 to Week 28 inclusive) including any evaluable unscheduled hemoglobin values that were taken during this period. Percentage of participants with Hgb response was defined as participants with mean Hgb within range (11-12 grams per deciliter during the evaluation period (Week 24 to Week 28 inclusive) and it was analyzed using Cochran-Mantel-Haenszel (CMH) chi-squared test. The percentage values presented has been rounded off.

    Time frame: Week 24 to Week 28

  4. Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Hodges-Lehmann Estimate)

    Percentage of days for which participant's Hgb was within the target range of 11-12 grams per deciliter during the evaluation period (Week 24 to Week 28 inclusive), including any unscheduled evaluable Hgb values that were taken during this time period. Percentage of time for which Hgb was within the target range (11-12 grams per deciliter) for a participant was calculated by dividing 'the total number of days that Hgb was within range during Week 24 to 28' by 'the total number of days the participant remained on treatment during Week 24 to 28'.

    Time frame: Week 24 to Week 28

  5. Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Mann-Whitney Estimate)

    Percentage of days for which participant's Hgb was within the target range of 11-12 grams per deciliter during the evaluation period (Week 24 to Week 28 inclusive), including any unscheduled evaluable Hgb values that were taken during this time period. Percentage of time for which Hgb was within the target range (11-12 grams per deciliter) for a participant was calculated by dividing 'the total number of days that Hgb was within range during Week 24 to 28' by 'the total number of days the participant remained on treatment during Week 24 to 28'

    Time frame: Week 24 to Week 28

  6. Change From Baseline in Post-randomization Hgb at Week 28

    Blood samples were collected at given time points for hemoglobin measurements. Change from Baseline in Hgb was analyzed using a mixed model repeated measures (MMRM) approach. Change from Baseline was calculated as Post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

    Time frame: Baseline (Day 1) and Week 28

  7. Rate of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria

    The incidence rate of participants permanently stopping randomized treatment due to meeting rescue criteria is presented.

    Time frame: Up to Week 28

  8. Change From Baseline by Domain and Single Item Scores on the Chronic Kidney Disease -Anemia Questionnaire (CKD-AQ) Symptom Questionnaire

    CKD-AQ is 21-item patient reported outcomes measure assessing symptoms \& symptom impact in participants with anemia associated with CKD.CKD-AQ identified 3 domains:1.Tired/Low Energy/Weak scale consisting of ten items;2.Chest Pain/Shortness of Breath scale consisting of four items and 3.Cognitive scale consisting of three items;Single items included: 4.Difficulty Sleeping;5.Difficulty Standing for long periods of time;6.Severity-Shortness of breath while sitting/resting;7.Time with Shortness of breath while not doing activity.Single-item measures were recorded based on 0-100 scoring with 0 is worst possible \& 100 is best possible score.Total domain score is calculated as average of items in each domain \& ranged from 0-100 where 0 is worst possible and 100 is best possible score.Change from Baseline was calculated as post-dose visit value minus Baseline.Baseline was latest non-missing pre-dose assessment on or before randomization date. Adjusted mean \& standard error is presented.

    Time frame: Baseline (Day 1) and Week 28

  9. Change From Baseline 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 on a 5-point disease severity scale (0=absent, 1=mild, 2=moderate, 3=severe, or 4=very severe). A higher score indicated worse outcome. Change from Baseline was calculated as Post-Dose visit value minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date. Adjusted mean and standard error is presented.

    Time frame: Baseline (Day 1) and Week 28

  10. Change From Baseline in the SF-36 Physical Functioning Domain

    The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following eight health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality, and general perception of health. Each domain is scored from 0 (poorer health) to 100 (better health). Physical functioning domain score ranges from 0-100; higher score indicates a better health state and better functioning. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

    Time frame: Baseline (Day 1) and Week 28

  11. Change From Baseline of the SF-36 Individual Items in the Vitality Domain

    The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following eight health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality, and general perception of health. Individual vitality items include: 1. Did you feel full of life?, 2. Did you have a lot of energy?, 3. Did you feel worn out?, 4. Did you feel tired?. Score of each item in the vitality domain ranges from 0-100; higher score indicates better health state and better functioning. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

    Time frame: Baseline (Day 1) and Week 28

  12. Number of Participants Currently Employed as Per Work Productivity and Activity Impairment Questionnaire: Anemic Symptoms Clinical Practice Version (WPAI-ANS-CPV)

    WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities. It contains 2 concepts-work productivity impairment measured via absenteeism(time missed from work), presenteeism(impairment at work) and regular daily activity impairment. WPAI questions (Q) were:1) currently employed,2) work time missed due to problem, 3) impairment while working due to problem, 4) overall work impairment due to problem, 5) activity impairment due to problem. WPAI generates 4 domain scores:percent (%) of work time missed(absenteeism),% of impairment while working(presenteeism),% of overall work impairment(absenteeism and presenteeism combined),% of activity impairment. Number of participants currently employed as per WPAI-ANS-CPV is presented.

    Time frame: Week 8, Week 12 and Week 28

  13. Change From Baseline in WPAI-ANS-CPV: Percent Time Missed From Work

    WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities. It contains 2 concepts-work productivity impairment measured via absenteeism (time missed from work), presenteeism (impairment at work) and regular daily activity impairment. WPAI questions (Q) were: 1) currently employed, 2) work time missed due to problem, 3) impairment while working due to problem, 4)overall work impairment due to problem, 5) activity impairment due to problem. Percent work time missed due to problem was a subscale and calculated as: Q2/(Q2+Q4) for those who were currently employed. Subscale score was expressed as an impairment percentage (range: 0-100%) where higher numbers indicate greater impairment and less productivity. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

    Time frame: Baseline (Day 1), Week 8, Week 12 and Week 28

  14. Change From Baseline in WPAI-ANS-CPV: Mean Hours Missed From Work in the Past 7 Days

    WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities. It contains 2 concepts-work productivity impairment measured via absenteeism (time missed from work), presenteeism (impairment at work) and regular daily activity impairment. WPAI Qs were: 1) currently employed, 2) work time missed due to problem, 3) impairment while working due to problem, 4) overall work impairment due to problem, 5) activity impairment due to problem. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

    Time frame: Baseline (Day 1), Week 8, Week 12 and Week 28

  15. Change From Baseline in WPAI: Percent Impairment at Work

    WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities.It contains 2 concepts-work productivity impairment measured via absenteeism(time missed from work),presenteeism(impairment at work) and regular daily activity impairment.WPAI Qs were:1)currently employed,2)work time missed due to problem,3)impairment while working due to problem,4)overall work impairment due to problem,5)activity impairment due to problem. % Impairment while Working due to Problem was subscale and calculated as: Q5/10 for those who were currently employed and actually worked in past 7 days. Subscale score was expressed as an impairment percentage (range: 0-100%) where higher numbers indicate greater impairment and less productivity. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before randomization date.

    Time frame: Baseline (Day 1), Week 8, Week 12 and Week 28

  16. Change From Baseline in WPAI: Percent Overall Work Impairment

    WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities. It contains 2 concepts-work productivity impairment measured via absenteeism (time missed from work), presenteeism (impairment at work) and regular daily activity impairment. WPAI Qs were: 1) currently employed, 2) work time missed due to problem, 3) impairment while working due to problem, 4) overall work impairment due to problem, 5) activity impairment due to problem. Percent overall work impairment due to problem was a subscale and calculated as: Q2/(Q2+Q4)+\[(1-Q2/(Q2+Q4))×(Q5/10)\] for those who were currently employed. Subscale score was expressed as an impairment percentage (range: 0-100%) where higher numbers indicate greater impairment. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before randomization date.

    Time frame: Baseline (Day 1), Week 8, Week 12 and Week 28

  17. Change From Baseline in WPAI: Percent Regular Daily Activity Impairment

    WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities.It contains 2 concepts-work productivity impairment measured via absenteeism (time missed from work), presenteeism (impairment at work) and regular daily activity impairment. WPAI Qs were: 1) currently employed, 2) work time missed due to problem, 3) impairment while working due to problem, 4) overall work impairment due to problem, 5) activity impairment due to problem. Percent activity impairment due to problem was a subscale and calculated as: Q5/10 for all respondents. Subscale score was expressed as an impairment percentage (range: 0-100%) where higher numbers indicate greater impairment. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before randomization date.

    Time frame: Baseline (Day 1), Week 8, Week 12 and Week 28

  18. Change From Baseline in EuroQol 5 Dimension 5 Level Health Utility Index (EQ-5D-5L) Utility Score

    The EQ-5D-5L is a self-assessment questionnaire, consisting of 5 items covering 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension is measured by a 5-point Likert scale (1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, and 5: extreme problems). The responses for the five dimension together form a five-figure description of health state. Each of these five-figure health states have attached valuation (utility score), expressed as single index on a scale from 0-1, where 1 is full health and 0 is worst health. The higher the score the better the health status. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

    Time frame: Baseline (Day 1) and Week 28

  19. Change From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score

    The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled 'the best health you can imagine' and 'the worst health you can imagine' at the time of completion. It is a self-assessment visual analogue scale, ranging from 0=worst imaginable to 100=best. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

    Time frame: Baseline (Day 1) and Week 28

  20. Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP) at Week 28

    SBP, DBP and MAP were measured with participants in a seated position after at least a 5-minute of rest. MAP is the average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

    Time frame: Baseline (Day 1) and Week 28

  21. Percentage of Participants With at Least One Blood Pressure (BP) Exacerbation Event

    Percentage of participants with at least one BP event is presented. BP exacerbation is defined as: SBP exacerbation: SBP \>= 25 mmHg increase from Baseline or SBP \>= 180 mmHg; DBP exacerbation: DBP \>= 15 mmHg increase from Baseline or DBP \>= 110 mmHg. Percentage of participants with at least one BP event is presented. The percentage values presented has been rounded off.

    Time frame: Up to Week 28

06

Results

Posted Nov 3, 2021

Participant flow

This was a multicenter study conducted at 142 centers in 14 countries. Participants were randomized to receive either Daprodustat or Placebo.

Participant flow — Overall Study
MilestonePlaceboDaprodustat
Started307307
Completed290300
Not completed177
Withdrew: Withdrawal by subject42
Withdrew: Physician decision10
Withdrew: Lost to follow-up72
Withdrew: Adverse event53

Outcome measures

PrimaryMean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28)

Blood samples were collected at given time points from participants for hemoglobin measurements. Evaluation period hemoglobin value was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 24 to Week 28 inclusive). For the primary analysis, the missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputations. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using the Analysis of Covariance (ANCOVA) model with terms for treatment, Baseline hemoglobin, and region.

Time frame:
Baseline (Day 1) and Week 24 to Week 28
Reported as:
Least squares mean · Grams per deciliter
Mean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28)
Grams per deciliterPlaceboDaprodustat
Mean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28)0.19 ± 0.0621.58 ± 0.061
Statistical analysis
  • Placebo vs Daprodustat · ANCOVA · p = <0.0001 · Ls mean difference: 1.40 · 95% CI 1.23 to 1.56Treatment group comparisons were based on a ANCOVA model with terms for treatment, Baseline hemoglobin, and region.
SecondaryPercentage of Participants With Hemoglobin Increase of >=1.0 Grams Per Deciliter From Baseline to Evaluation Period

Blood samples were collected at given time points for hemoglobin measurements. Evaluation period hemoglobin value was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 24 to Week 28 inclusive). For the primary analysis, the missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputations. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date. Percentage of participants with hemoglobin increase of \>=1.0 grams per deciliter from Baseline to evaluation period was analyzed using Cochran-Mantel-Haenszel (CMH) chi-squared test. The percentage values presented has been rounded off.

Time frame:
Baseline (Day 1) and Week 24 to Week 28
Reported as:
Number · Percentage of participants
Percentage of Participants With Hemoglobin Increase of >=1.0 Grams Per Deciliter From Baseline to Evaluation Period
Percentage of participantsPlaceboDaprodustat
Percentage of Participants With Hemoglobin Increase of >=1.0 Grams Per Deciliter From Baseline to Evaluation Period1877
Statistical analysis
  • Placebo vs Daprodustat · Cochran-Mantel-Haenszel · p = <0.0001 (One-sided p-value was based on test of null hypothesis: (Daprodustat - Placebo) \<=0 versus alternative: difference \> 0) · Difference in response rate: 0.56 · 95% CI 0.49 to 0.63Treatment group comparisons were based on a Cochran-Mantel-Haenszel test adjusted for treatment group and region.
SecondaryChange From Baseline in Short Form-36 (SF-36) Questionnaire Vitality Domain Score by Traditional Scoring at Week 28

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the 8 health domains: Physical Functioning, Role-Physical (role limitations caused by physical problems), Social Functioning, Bodily Pain, Mental Health, Role-Emotional (role limitations caused by emotional problems), Vitality, and General Perception of Health.Each domain is scored from 0 (poorer health) to 100 (better health). Vitality domain score ranges from 0-100; higher score indicates a better health state \& better functioning. Change from Baseline was calculated as Post-Dose Visit Value at Week 28 minus Baseline. For primary analysis, the missing on-treatment Week 28 SF-36 Vitality domain scores were imputed using pre-specified multiple imputations. Baseline value was latest non-missing pre-dose assessment on or before randomization date. Analysis was performed using ANCOVA model with terms for treatment, Baseline score, and region.

Time frame:
Baseline (Day 1) and Week 28
Reported as:
Least squares mean · Scores on a scale
Change From Baseline in Short Form-36 (SF-36) Questionnaire Vitality Domain Score by Traditional Scoring at Week 28
Scores on a scalePlaceboDaprodustat
Change From Baseline in Short Form-36 (SF-36) Questionnaire Vitality Domain Score by Traditional Scoring at Week 281.93 ± 1.1617.29 ± 1.121
Statistical analysis
  • Placebo vs Daprodustat · ANCOVA · p = 0.0005 (One-sided p-value based on test of null hypothesis:(Daprodustat-Placebo) \<= 0 vs alternative: difference \> 0.) · Ls mean difference: 5.36 · 95% CI 2.17 to 8.56Treatment group comparisons were based on ANCOVA model with terms for treatment, Baseline score, and region.
SecondaryPercentage of Participants With Hgb Response (Hgb in the 11-12 Grams/Deciliter Range) During Evaluation Period (Week 24 to Week 28 Inclusive)

Mean hemoglobin during the evaluation period was defined as the mean of all evaluable hemoglobin values during the evaluation period (Week 24 to Week 28 inclusive) including any evaluable unscheduled hemoglobin values that were taken during this period. Percentage of participants with Hgb response was defined as participants with mean Hgb within range (11-12 grams per deciliter during the evaluation period (Week 24 to Week 28 inclusive) and it was analyzed using Cochran-Mantel-Haenszel (CMH) chi-squared test. The percentage values presented has been rounded off.

Time frame:
Week 24 to Week 28
Reported as:
Number · Percentage of participants
Percentage of Participants With Hgb Response (Hgb in the 11-12 Grams/Deciliter Range) During Evaluation Period (Week 24 to Week 28 Inclusive)
Percentage of participantsPlaceboDaprodustat
Percentage of Participants With Hgb Response (Hgb in the 11-12 Grams/Deciliter Range) During Evaluation Period (Week 24 to Week 28 Inclusive)852
Statistical analysis
  • Placebo vs Daprodustat · Cochran-Mantel-Haenszel · p = <0.0001 (One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus alternative: difference \>0.) · Difference in response rate: 0.45 · 95% CI 0.37 to 0.52Treatment group comparisons are based on a Cochran-Mantel-Haenszel test adjusted for treatment group, and region
SecondaryPercentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Hodges-Lehmann Estimate)

Percentage of days for which participant's Hgb was within the target range of 11-12 grams per deciliter during the evaluation period (Week 24 to Week 28 inclusive), including any unscheduled evaluable Hgb values that were taken during this time period. Percentage of time for which Hgb was within the target range (11-12 grams per deciliter) for a participant was calculated by dividing 'the total number of days that Hgb was within range during Week 24 to 28' by 'the total number of days the participant remained on treatment during Week 24 to 28'.

Time frame:
Week 24 to Week 28
Reported as:
Median · Percentage of days
Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Hodges-Lehmann Estimate)
Percentage of daysPlaceboDaprodustat
Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Hodges-Lehmann Estimate)0.00 (0.0 to 100.0)53.59 (0.0 to 100.0)
Statistical analysis
  • Placebo vs Daprodustat · Hodges-Lehmann Estimate · Difference in treatment effect: 38.80 · 95% CI 25.00 to 54.55Hodges-Lehmann Estimate of treatment difference has been reported.
SecondaryPercentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Mann-Whitney Estimate)

Percentage of days for which participant's Hgb was within the target range of 11-12 grams per deciliter during the evaluation period (Week 24 to Week 28 inclusive), including any unscheduled evaluable Hgb values that were taken during this time period. Percentage of time for which Hgb was within the target range (11-12 grams per deciliter) for a participant was calculated by dividing 'the total number of days that Hgb was within range during Week 24 to 28' by 'the total number of days the participant remained on treatment during Week 24 to 28'

Time frame:
Week 24 to Week 28
Reported as:
Median · Percentage of days
Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Mann-Whitney Estimate)
Percentage of daysPlaceboDaprodustat
Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Mann-Whitney Estimate)0.00 (0.0 to 100.0)53.59 (0.0 to 100.0)
Statistical analysis
  • Placebo vs Daprodustat · van Elteren test · p = <0.0001 (One-sided superiority p-value from the van Elteren test) · Difference in treatment effect: 0.768 · 95% CI 0.729 to 0.806Mann-Whitney estimate of the treatment difference stratified by region has been presented.
SecondaryChange From Baseline in Post-randomization Hgb at Week 28

Blood samples were collected at given time points for hemoglobin measurements. Change from Baseline in Hgb was analyzed using a mixed model repeated measures (MMRM) approach. Change from Baseline was calculated as Post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

Time frame:
Baseline (Day 1) and Week 28
Reported as:
Least squares mean · Grams per deciliter
Change From Baseline in Post-randomization Hgb at Week 28
Grams per deciliterPlaceboDaprodustat
Change From Baseline in Post-randomization Hgb at Week 280.20 ± 0.0701.56 ± 0.069
Statistical analysis
  • Placebo vs Daprodustat · MMRM · p = <0.0001 (One-sided superiority p-value from the MMRM model) · Ls mean difference: 1.36 · 95% CI 1.16 to 1.55Treatment group comparisons were based on MMRM fitted from Baseline up to Week 28, with factors for treatment, time, region, Baseline Hb and Baseline Hb by time and treatment by time interactions.
SecondaryRate of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria

The incidence rate of participants permanently stopping randomized treatment due to meeting rescue criteria is presented.

Time frame:
Up to Week 28
Reported as:
Number · Events per 100 person year
Rate of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria
Events per 100 person yearPlaceboDaprodustat
Rate of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria18.88 (12.33 to 27.66)1.33 (0.16 to 4.82)
Statistical analysis
  • Placebo vs Daprodustat · Wald test · p = 0.0002 (One-sided p-value was based on Wald test of null hypothesis: (Daprodustat/Placebo) \>=1 versus alternative: ratio\<1.) · Hazard ratio (hr): 0.07 · 95% CI 0.02 to 0.30Hazard ratio was estimated using a Cox proportional hazard regression model adjusted for treatment group and region.
SecondaryChange From Baseline by Domain and Single Item Scores on the Chronic Kidney Disease -Anemia Questionnaire (CKD-AQ) Symptom Questionnaire

CKD-AQ is 21-item patient reported outcomes measure assessing symptoms \& symptom impact in participants with anemia associated with CKD.CKD-AQ identified 3 domains:1.Tired/Low Energy/Weak scale consisting of ten items;2.Chest Pain/Shortness of Breath scale consisting of four items and 3.Cognitive scale consisting of three items;Single items included: 4.Difficulty Sleeping;5.Difficulty Standing for long periods of time;6.Severity-Shortness of breath while sitting/resting;7.Time with Shortness of breath while not doing activity.Single-item measures were recorded based on 0-100 scoring with 0 is worst possible \& 100 is best possible score.Total domain score is calculated as average of items in each domain \& ranged from 0-100 where 0 is worst possible and 100 is best possible score.Change from Baseline was calculated as post-dose visit value minus Baseline.Baseline was latest non-missing pre-dose assessment on or before randomization date. Adjusted mean \& standard error is presented.

Time frame:
Baseline (Day 1) and Week 28
Reported as:
Mean · Scores on a scale
Change From Baseline by Domain and Single Item Scores on the Chronic Kidney Disease -Anemia Questionnaire (CKD-AQ) Symptom Questionnaire
Scores on a scalePlaceboDaprodustat
Tired/Low Energy/Weak Domain2.81 ± 1.1328.72 ± 1.086
Chest Pain/Shortness of Breath Domain0.62 ± 0.9713.55 ± 0.932
Cognitive Domain0.48 ± 1.0424.27 ± 0.999
Difficulty in Sleeping2.61 ± 1.6435.22 ± 1.577
Difficulty Standing for Long Periods of Time1.55 ± 1.6306.19 ± 1.563
Severity-Shortness of Breath, Sitting/Resting0.43 ± 0.9953.11 ± 0.954
Time with Shortness of BreathnotDoingActivity0.29 ± 1.0832.30 ± 1.037
Statistical analysis
  • Placebo vs Daprodustat · MMRM · p = <0.0001 (One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus alternative: difference \>0.) · Mean difference (net): 5.91 · 95% CI 2.83 to 9.00Analysis was performed by MMRM with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions for Tired/Low Energy/Weak domain.
  • Placebo vs Daprodustat · MMRM · p = 0.0152 (One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus alternative: difference \>0.) · Mean difference (net): 2.93 · 95% CI 0.28 to 5.57Analysis was performed by MMRM with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions for Chest Pain/Shortness of Breath Domain.
  • Placebo vs Daprodustat · MMRM · p = 0.0045 (One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus alternative: difference \>0.) · Mean difference (net): 3.79 · 95% CI 0.95 to 6.63Analysis was performed by MMRM with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions for Cognitive Domain.
  • Placebo vs Daprodustat · MMRM · p = 0.1267 (One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus alternative: difference \>0.) · Mean difference (net): 2.61 · 95% CI -1.87 to 7.09Analysis was performed by MMRM with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions for Difficulty Sleeping
  • Placebo vs Daprodustat · MMRM · p = 0.0203 (One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus alternative: difference \>0.) · Mean difference (net): 4.64 · 95% CI 0.20 to 9.09Analysis was performed by MMRM with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions for Difficulty Standing for Long Periods of Time
  • Placebo vs Daprodustat · MMRM · p = 0.0266 (One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus alternative: difference \>0.) · Mean difference (net): 2.68 · 95% CI -0.04 to 5.39Analysis was performed by MMRM with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions for Severity of Shortness of Breath While Sitting or Resting
  • Placebo vs Daprodustat · MMRM · p = 0.0907 (One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus alternative: difference \>0.) · Mean difference (net): 2.01 · 95% CI -0.94 to 4.96Analysis was performed by MMRM with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions for Time with Shortness of Breath While not Doing an Activity
SecondaryChange From Baseline 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 on a 5-point disease severity scale (0=absent, 1=mild, 2=moderate, 3=severe, or 4=very severe). A higher score indicated worse outcome. Change from Baseline was calculated as Post-Dose visit value minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date. Adjusted mean and standard error is presented.

Time frame:
Baseline (Day 1) and Week 28
Reported as:
Least squares mean · Scores on a scale
Change From Baseline in Patient Global Impression of Severity (PGI-S)
Scores on a scalePlaceboDaprodustat
Change From Baseline in Patient Global Impression of Severity (PGI-S)-0.04 ± 0.055-0.18 ± 0.052
Statistical analysis
  • Placebo vs Daprodustat · MMRM · p = 0.0391 (One-sided p-value was based on test of null hypothesis: (Daprodustat-rhEPO) \>=0 versus alternative: difference \<0) · Mean difference (net): -0.13 · 95% CI -0.28 to 0.02MMRM fitted from Baseline up to Week 28 with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions.
SecondaryChange From Baseline in the SF-36 Physical Functioning Domain

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following eight health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality, and general perception of health. Each domain is scored from 0 (poorer health) to 100 (better health). Physical functioning domain score ranges from 0-100; higher score indicates a better health state and better functioning. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

Time frame:
Baseline (Day 1) and Week 28
Reported as:
Least squares mean · Scores on a scale
Change From Baseline in the SF-36 Physical Functioning Domain
Scores on a scalePlaceboDaprodustat
Change From Baseline in the SF-36 Physical Functioning Domain1.23 ± 1.3543.80 ± 1.298
Statistical analysis
  • Placebo vs Daprodustat · MMRM · p = 0.0858 (One sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) \<=0 vs. alternative: difference \>0.) · Mean difference (net): 2.57 · 95% CI -1.12 to 6.26MMRM fitted from Baseline up to Week 28 with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions.
SecondaryChange From Baseline of the SF-36 Individual Items in the Vitality Domain

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following eight health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality, and general perception of health. Individual vitality items include: 1. Did you feel full of life?, 2. Did you have a lot of energy?, 3. Did you feel worn out?, 4. Did you feel tired?. Score of each item in the vitality domain ranges from 0-100; higher score indicates better health state and better functioning. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

Time frame:
Baseline (Day 1) and Week 28
Reported as:
Least squares mean · Scores on a scale
Change From Baseline of the SF-36 Individual Items in the Vitality Domain
Scores on a scalePlaceboDaprodustat
Did you feel full of life?-0.02 ± 0.0700.16 ± 0.067
Did you have a lot of energy?0.09 ± 0.0660.26 ± 0.063
Did you feel worn out?0.16 ± 0.0670.34 ± 0.064
Did you feel tired?0.08 ± 0.0600.34 ± 0.057
Statistical analysis
  • Placebo vs Daprodustat · MMRM · p = 0.0357 (One sided p-value based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus alternative: difference \>0.) · Mean difference (net): 0.17 · 95% CI -0.02 to 0.36MMRM fitted from Baseline up to Week 28 with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions for Did you feel full of life?.
  • Placebo vs Daprodustat · MMRM · p = 0.0328 (One-sided p-value based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus alternative: difference \>0.) · Mean difference (net): 0.17 · 95% CI -0.01 to 0.35MMRM fitted from Baseline up to Week 28 with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions for Did you have a lot of energy?.
  • Placebo vs Daprodustat · MMRM · p = 0.0252 (One-sided p-value based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus alternative: difference \>0.) · Mean difference (net): 0.18 · 95% CI 0.00 to 0.37MMRM fitted from Baseline up to Week 28 with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions for Did you feel worn out?.
  • Placebo · MMRM · p = 0.0010 (One-sided p-value based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus alternative: difference \>0.) · Mean difference (net): 0.26 · 95% CI 0.10 to 0.42MMRM fitted from Baseline up to Week 28 with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions for Did you feel tired?.
SecondaryNumber of Participants Currently Employed as Per Work Productivity and Activity Impairment Questionnaire: Anemic Symptoms Clinical Practice Version (WPAI-ANS-CPV)

WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities. It contains 2 concepts-work productivity impairment measured via absenteeism(time missed from work), presenteeism(impairment at work) and regular daily activity impairment. WPAI questions (Q) were:1) currently employed,2) work time missed due to problem, 3) impairment while working due to problem, 4) overall work impairment due to problem, 5) activity impairment due to problem. WPAI generates 4 domain scores:percent (%) of work time missed(absenteeism),% of impairment while working(presenteeism),% of overall work impairment(absenteeism and presenteeism combined),% of activity impairment. Number of participants currently employed as per WPAI-ANS-CPV is presented.

Time frame:
Week 8, Week 12 and Week 28
Reported as:
Count of participants · Participants
Number of Participants Currently Employed as Per Work Productivity and Activity Impairment Questionnaire: Anemic Symptoms Clinical Practice Version (WPAI-ANS-CPV)
ParticipantsPlaceboDaprodustat
Week 8, No, n=249, 250195204
Week 8, Yes, n=249, 2505446
Week 12, No, n=234, 251183212
Week 12, Yes, n=234, 2515139
Week 28, No, n=193, 213158178
Week 28, Yes, n=193, 2133535
SecondaryChange From Baseline in WPAI-ANS-CPV: Percent Time Missed From Work

WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities. It contains 2 concepts-work productivity impairment measured via absenteeism (time missed from work), presenteeism (impairment at work) and regular daily activity impairment. WPAI questions (Q) were: 1) currently employed, 2) work time missed due to problem, 3) impairment while working due to problem, 4)overall work impairment due to problem, 5) activity impairment due to problem. Percent work time missed due to problem was a subscale and calculated as: Q2/(Q2+Q4) for those who were currently employed. Subscale score was expressed as an impairment percentage (range: 0-100%) where higher numbers indicate greater impairment and less productivity. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

Time frame:
Baseline (Day 1), Week 8, Week 12 and Week 28
Reported as:
Mean · Percentage of time
Change From Baseline in WPAI-ANS-CPV: Percent Time Missed From Work
Percentage of timePlaceboDaprodustat
Week 8, n=50, 39-2.4 ± 28.40-6.1 ± 24.92
Week 12, n=46, 310.9 ± 28.794.2 ± 27.96
Week 28, n=28, 250.0 ± 33.590.3 ± 31.01
SecondaryChange From Baseline in WPAI-ANS-CPV: Mean Hours Missed From Work in the Past 7 Days

WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities. It contains 2 concepts-work productivity impairment measured via absenteeism (time missed from work), presenteeism (impairment at work) and regular daily activity impairment. WPAI Qs were: 1) currently employed, 2) work time missed due to problem, 3) impairment while working due to problem, 4) overall work impairment due to problem, 5) activity impairment due to problem. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

Time frame:
Baseline (Day 1), Week 8, Week 12 and Week 28
Reported as:
Mean · Percentage of hours
Change From Baseline in WPAI-ANS-CPV: Mean Hours Missed From Work in the Past 7 Days
Percentage of hoursPlaceboDaprodustat
Week 8, n=50, 390.1 ± 18.46-1.8 ± 11.88
Week 12, n=46, 311.4 ± 14.072.4 ± 16.83
Week 28, n=28, 250.3 ± 19.901.0 ± 14.24
SecondaryChange From Baseline in WPAI: Percent Impairment at Work

WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities.It contains 2 concepts-work productivity impairment measured via absenteeism(time missed from work),presenteeism(impairment at work) and regular daily activity impairment.WPAI Qs were:1)currently employed,2)work time missed due to problem,3)impairment while working due to problem,4)overall work impairment due to problem,5)activity impairment due to problem. % Impairment while Working due to Problem was subscale and calculated as: Q5/10 for those who were currently employed and actually worked in past 7 days. Subscale score was expressed as an impairment percentage (range: 0-100%) where higher numbers indicate greater impairment and less productivity. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before randomization date.

Time frame:
Baseline (Day 1), Week 8, Week 12 and Week 28
Reported as:
Mean · Percentage of impairment
Change From Baseline in WPAI: Percent Impairment at Work
Percentage of impairmentPlaceboDaprodustat
Week 8, n=45, 32-5.1 ± 18.42-11.3 ± 24.06
Week 12, n=41, 26-4.6 ± 18.99-8.8 ± 23.38
Week 28, n=24, 20-9.6 ± 25.62-9.0 ± 22.92
SecondaryChange From Baseline in WPAI: Percent Overall Work Impairment

WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities. It contains 2 concepts-work productivity impairment measured via absenteeism (time missed from work), presenteeism (impairment at work) and regular daily activity impairment. WPAI Qs were: 1) currently employed, 2) work time missed due to problem, 3) impairment while working due to problem, 4) overall work impairment due to problem, 5) activity impairment due to problem. Percent overall work impairment due to problem was a subscale and calculated as: Q2/(Q2+Q4)+\[(1-Q2/(Q2+Q4))×(Q5/10)\] for those who were currently employed. Subscale score was expressed as an impairment percentage (range: 0-100%) where higher numbers indicate greater impairment. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before randomization date.

Time frame:
Baseline (Day 1), Week 8, Week 12 and Week 28
Reported as:
Mean · Percentage of impairment
Change From Baseline in WPAI: Percent Overall Work Impairment
Percentage of impairmentPlaceboDaprodustat
Week 8, n=45, 32-4.3 ± 24.04-12.0 ± 25.90
Week 12, n=41, 260.5 ± 25.81-3.2 ± 33.35
Week 28, n=24, 20-9.3 ± 37.45-8.4 ± 19.12
SecondaryChange From Baseline in WPAI: Percent Regular Daily Activity Impairment

WPAI-ANS-CPV is anemia specific questionnaire designed as self-reported quantitative assessment of social functioning related to work and regular daily activities.It contains 2 concepts-work productivity impairment measured via absenteeism (time missed from work), presenteeism (impairment at work) and regular daily activity impairment. WPAI Qs were: 1) currently employed, 2) work time missed due to problem, 3) impairment while working due to problem, 4) overall work impairment due to problem, 5) activity impairment due to problem. Percent activity impairment due to problem was a subscale and calculated as: Q5/10 for all respondents. Subscale score was expressed as an impairment percentage (range: 0-100%) where higher numbers indicate greater impairment. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before randomization date.

Time frame:
Baseline (Day 1), Week 8, Week 12 and Week 28
Reported as:
Mean · Percentage of impairment
Change From Baseline in WPAI: Percent Regular Daily Activity Impairment
Percentage of impairmentPlaceboDaprodustat
Week 8, n=243, 248-4.6 ± 23.67-7.7 ± 24.53
Week 12, n=228, 246-5.2 ± 25.40-8.6 ± 24.58
Week 28, n=187, 210-6.7 ± 28.93-12.2 ± 27.50
SecondaryChange From Baseline in EuroQol 5 Dimension 5 Level Health Utility Index (EQ-5D-5L) Utility Score

The EQ-5D-5L is a self-assessment questionnaire, consisting of 5 items covering 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension is measured by a 5-point Likert scale (1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, and 5: extreme problems). The responses for the five dimension together form a five-figure description of health state. Each of these five-figure health states have attached valuation (utility score), expressed as single index on a scale from 0-1, where 1 is full health and 0 is worst health. The higher the score the better the health status. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

Time frame:
Baseline (Day 1) and Week 28
Reported as:
Least squares mean · Scores on a scale
Change From Baseline in EuroQol 5 Dimension 5 Level Health Utility Index (EQ-5D-5L) Utility Score
Scores on a scalePlaceboDaprodustat
Change From Baseline in EuroQol 5 Dimension 5 Level Health Utility Index (EQ-5D-5L) Utility Score0.01 ± 0.0150.03 ± 0.014
Statistical analysis
  • Placebo vs Daprodustat · MMRM · p = 0.1098 (One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) \<=0 versus. alternative: difference \>0.) · Mean difference (net): 0.03 · 95% CI -0.02 to 0.07Based on MMRM model fitted from Baseline up to Week 28 with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions.
SecondaryChange From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score

The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled 'the best health you can imagine' and 'the worst health you can imagine' at the time of completion. It is a self-assessment visual analogue scale, ranging from 0=worst imaginable to 100=best. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

Time frame:
Baseline (Day 1) and Week 28
Reported as:
Least squares mean · Scores on a scale
Change From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score
Scores on a scalePlaceboDaprodustat
Change From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score0.80 ± 1.4275.30 ± 1.373
Statistical analysis
  • Placebo vs Daprodustat · MMRM · p = 0.0120 (One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) \<=0 vs. alternative: difference \>0.) · Mean difference (net): 4.50 · 95% CI 0.60 to 8.40MMRM model fitted from Baseline up to Week 28 with factors for treatment, time, region, Baseline value and Baseline value by time and treatment by time interactions.
SecondaryChange From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP) at Week 28

SBP, DBP and MAP were measured with participants in a seated position after at least a 5-minute of rest. MAP is the average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as post-dose visit value minus Baseline. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date.

Time frame:
Baseline (Day 1) and Week 28
Reported as:
Least squares mean · Millimeters of mercury (mmHg)
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP) at Week 28
Millimeters of mercury (mmHg)PlaceboDaprodustat
SBP-0.63 ± 1.045-0.23 ± 0.981
DBP-0.96 ± 0.6250.84 ± 0.587
MAP-0.82 ± 0.6740.49 ± 0.632
Statistical analysis
  • Placebo vs Daprodustat · MMRM · p = 0.6106 (One-sided p-value was based on test of null hypothesis: (Daprodustat - Placebo) \>= 0 versus alternative: difference \<0) · Mean difference (net): 0.40 · 95% CI -2.42 to 3.22MMRM model fitted from Baseline up to Week 28, with factors for treatment, time, region, Baseline SBP and Baseline SBP by time and treatment by time interactions.
  • Placebo vs Daprodustat · MMRM · p = 0.9819 (One-sided p-value was based on test of null hypothesis: (Daprodustat - Placebo) \>= 0 versus alternative: difference \< 0) · Mean difference (net): 1.80 · 95% CI 0.12 to 3.49MMRM model fitted from Baseline up to Week 28, with factors for treatment, time, region, Baseline DBP and Baseline DBP by time and treatment by time interactions.
  • Placebo vs Daprodustat · MMRM · p = 0.9215 (One-sided p-value was based on test of null hypothesis: (Daprodustat - Placebo) \>= 0 versus alternative: difference \<0) · Mean difference (net): 1.31 · 95% CI -0.51 to 3.13MMRM model fitted from Baseline up to Week 28, with factors for treatment, time, region, Baseline MAP and Baseline MAP by time and treatment by time interactions.
SecondaryPercentage of Participants With at Least One Blood Pressure (BP) Exacerbation Event

Percentage of participants with at least one BP event is presented. BP exacerbation is defined as: SBP exacerbation: SBP \>= 25 mmHg increase from Baseline or SBP \>= 180 mmHg; DBP exacerbation: DBP \>= 15 mmHg increase from Baseline or DBP \>= 110 mmHg. Percentage of participants with at least one BP event is presented. The percentage values presented has been rounded off.

Time frame:
Up to Week 28
Reported as:
Number · Percentage of participants
Percentage of Participants With at Least One Blood Pressure (BP) Exacerbation Event
Percentage of participantsPlaceboDaprodustat
Percentage of Participants With at Least One Blood Pressure (BP) Exacerbation Event2632
Statistical analysis
  • Placebo vs Daprodustat · Cochran-Mantel-Haenszel · p = 0.0680 (One-sided p-value based on test of null hypothesis: (Daprodustat - Placebo) \<= 0 versus alternative: difference \> 0.) · Difference in response rate: 0.06 · 95% CI -0.02 to 0.13Cochran-Mantel-Haenszel test was performed for treatment group comparison.

Adverse events

Collected over All cause mortality, serious adverse events (SAEs) and non-serious AEs were collected up to follow-up (Week 32).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo16/306 (5.2%)68/306 (22.2%)44/306 (14.4%)
Daprodustat10/308 (3.2%)62/308 (20.1%)49/308 (15.9%)
Most frequent serious events
Showing 10 of 120
Most frequent serious events
EventPlaceboDaprodustat
AnaemiaBlood and lymphatic system disorders8/3062/308
Renal failureRenal and urinary disorders6/3062/308
Acute kidney injuryRenal and urinary disorders5/3065/308
Cardiac failure acuteCardiac disorders4/3060/308
Urinary tract infectionInfections and infestations4/3062/308
Cardiac failureCardiac disorders1/3064/308
HypotensionVascular disorders3/3060/308
Cardiac failure congestiveCardiac disorders2/3063/308
Atrial fibrillationCardiac disorders0/3063/308
Acute pulmonary oedemaRespiratory, thoracic and mediastinal disorders1/3063/308
Most frequent other events
Most frequent other events
EventPlaceboDaprodustat
DiarrhoeaGastrointestinal disorders17/30624/308
Oedema peripheralGeneral disorders21/30612/308
HypertensionVascular disorders14/30621/308

Baseline characteristics

Age, Continuous
Age, Continuous(Years)PlaceboDaprodustatTotal
Mean66.6 ± 12.9365.3 ± 13.4365.9 ± 13.19
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboDaprodustatTotal
Female178176354
Male129131260
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboDaprodustatTotal
AMERICAN INDIAN OR ALASKA NATIVE343468
ASIAN: CENTRAL/SOUTH ASIAN HERITAGE369
ASIAN: JAPANESE/EASTASIAN/SOUTHEAST ASIAN HERITAGE242448
ASIAN: MIXED ASIAN RACE101
BLACK OR AFRICAN AMERICAN474491
NATIVE HAWAIIAN/OTHER PACIFIC ISLANDER101
WHITE195197392
BLACK OR AFRICAN AMERICAN AND WHITE224
07

Study locations

168 sites
  • GSK Investigational Site
    Homewood, Alabama 35209, United States
  • GSK Investigational Site
    Little Rock, Arkansas 72204, United States
  • GSK Investigational Site
    Downey, California 90242, United States
  • GSK Investigational Site
    Fresno, California 93720, United States
  • GSK Investigational Site
    Lynwood, California 90262, United States
  • GSK Investigational Site
    Northridge, California 91324, United States
  • GSK Investigational Site
    Northridge, California 91325, United States
  • GSK Investigational Site
    Riverside, California 82503, United States
  • GSK Investigational Site
    Salinas, California 93901, United States
  • GSK Investigational Site
    Santa Ana, California 92704, United States
  • GSK Investigational Site
    Denver, Colorado 80230, United States
  • GSK Investigational Site
    Hartford, Connecticut 06112, United States
  • GSK Investigational Site
    Middlebury, Connecticut 06762, United States
  • GSK Investigational Site
    Coral Springs, Florida 33067, United States
  • GSK Investigational Site
    Hollywood, Florida 33024, United States
  • GSK Investigational Site
    Kissimmee, Florida 34741, United States
  • GSK Investigational Site
    Lauderdale Lakes, Florida 33313, United States
  • GSK Investigational Site
    Pembroke Pines, Florida 33028, United States
  • GSK Investigational Site
    Tampa, Florida 33614, United States
  • GSK Investigational Site
    Adairsville, Georgia 30103, United States
  • GSK Investigational Site
    Macon, Georgia 31201, United States
  • GSK Investigational Site
    Macon, Georgia 31217, United States
  • GSK Investigational Site
    Statesboro, Georgia 30458, United States
  • GSK Investigational Site
    Indianapolis, Indiana 46260, United States
  • GSK Investigational Site
    Overland Park, Kansas 66210, United States
  • GSK Investigational Site
    Buckley, Michigan 49620, United States
  • GSK Investigational Site
    Detroit, Michigan 48202, United States
  • GSK Investigational Site
    Saint Clair Shores, Michigan 48081, United States
  • GSK Investigational Site
    Brookhaven, Mississippi 39601, United States
  • GSK Investigational Site
    Saint Louis, Missouri 63136, United States
  • GSK Investigational Site
    Rochester, New Hampshire 03867, United States
  • GSK Investigational Site
    Asheville, North Carolina 28801, United States
  • GSK Investigational Site
    Charlotte, North Carolina 28262, United States
  • GSK Investigational Site
    Durham, North Carolina 27704, United States
  • GSK Investigational Site
    Midwest City, Oklahoma 73130, United States
  • GSK Investigational Site
    Oklahoma City, Oklahoma 73112, United States
  • GSK Investigational Site
    Beaver, Pennsylvania 15009, United States
  • GSK Investigational Site
    Duncansville, Pennsylvania 16635, United States
  • GSK Investigational Site
    Scottdale, Pennsylvania 15683, United States
  • GSK Investigational Site
    Smithfield, Pennsylvania 15478, United States
  • GSK Investigational Site
    West Reading, Pennsylvania 19611, United States
  • GSK Investigational Site
    Orangeburg, South Carolina 29118, United States
  • GSK Investigational Site
    Kingsport, Tennessee 37660, United States
  • GSK Investigational Site
    Memphis, Tennessee 38163, United States
  • GSK Investigational Site
    DeSoto, Texas 75115, United States
  • GSK Investigational Site
    El Paso, Texas 79935, United States
  • GSK Investigational Site
    McAllen, Texas 78503, United States
  • GSK Investigational Site
    Waxahachie, Texas 75165, United States
  • GSK Investigational Site
    Norfolk, Virginia 23502, United States
  • GSK Investigational Site
    Ciudad Autonoma de Buenos Aires, Buenos Aires C1128AAF, Argentina
  • GSK Investigational Site
    Ciudad Autonoma de Buenos Aires, Buenos Aires C1425AGC, Argentina
  • GSK Investigational Site
    Mar del Plata, Buenos Aires 7600, Argentina
  • GSK Investigational Site
    Mar del Plata, Buenos Aires B7600FZN, Argentina
  • GSK Investigational Site
    San Nicolas, Buenos Aires B2900DMH, Argentina
  • GSK Investigational Site
    Cordoba, Córdova 5003, Argentina
  • GSK Investigational Site
    Rosario, Santa Fe S2000DEJ, Argentina
  • GSK Investigational Site
    Santa Fe, 3000, Argentina
  • GSK Investigational Site
    Sydney, New South Wales 2010, Australia
  • GSK Investigational Site
    Heidelberg, Victoria 3084, Australia
  • GSK Investigational Site
    Parkville, Victoria 3050, Australia
  • GSK Investigational Site
    Murdoch, Western Australia 6150, Australia
  • GSK Investigational Site
    Fitzroy, 3065, Australia
  • GSK Investigational Site
    Feira de Santana., Bahia 44001-584, Brazil
  • GSK Investigational Site
    Salvador, Bahia 40415-065, Brazil
  • GSK Investigational Site
    Vitoria, Espírito Santo 29055450, Brazil
  • GSK Investigational Site
    Ribeirão Preto, São Paulo 14025170, Brazil
  • GSK Investigational Site
    Santo André - SP, São Paulo 09080-110, Brazil
  • GSK Investigational Site
    Sao Jose do Rio Preto, São Paulo 15015200, Brazil
  • GSK Investigational Site
    Sao Jose do Rio Preto, São Paulo 15090-000, Brazil
  • GSK Investigational Site
    São Bernardo do Campo, São Paulo 09715090, Brazil
  • GSK Investigational Site
    São Paulo, 04038002, Brazil
  • GSK Investigational Site
    Victoria, British Columbia V8V 4A1, Canada
  • GSK Investigational Site
    Brampton, Ontario L6T 0G1, Canada
  • GSK Investigational Site
    Guelph, Ontario N1H 1B1, Canada
  • GSK Investigational Site
    Kitchener, Ontario N2H 5Z8, Canada
  • GSK Investigational Site
    Ottawa, Ontario K1H 1A2, Canada
  • GSK Investigational Site
    Sarnia, Ontario N7T 4X3, Canada
  • GSK Investigational Site
    Sudbury, Ontario P3A-1W8, Canada
  • GSK Investigational Site
    Toronto, Ontario M5B 1W8, Canada
  • GSK Investigational Site
    Toronto, Ontario M9N 1N8, Canada
  • GSK Investigational Site
    Toronto, Ontario M9V 4B4, Canada
  • GSK Investigational Site
    Montréal, Quebec H1M 1B1, Canada
  • GSK Investigational Site
    Quebec city, Quebec G2J 0C4, Canada
  • GSK Investigational Site
    St-Charles-Borromée, Quebec J6E 2B4, Canada
  • GSK Investigational Site
    Quebec, G3K 2P8, Canada
  • GSK Investigational Site
    Grenoble cedex 9, 38043, France
  • GSK Investigational Site
    Le Mans cedex 9, 72037, France
  • GSK Investigational Site
    Marseille cedex 5, 13385, France
  • GSK Investigational Site
    Melun, 77000, France
  • GSK Investigational Site
    Mulhouse cedex, 68070, France
  • GSK Investigational Site
    Nantes Cedex 1, 44093, France
  • GSK Investigational Site
    Nice Cedex 1, 06001, France
  • GSK Investigational Site
    Saint-Priest en Jarez, 42270, France
  • GSK Investigational Site
    Catanzaro, Calabria 88100, Italy
  • GSK Investigational Site
    Napoli, Campania 80131, Italy
  • GSK Investigational Site
    Bologna, Emilia-Romagna 40138, Italy
  • GSK Investigational Site
    Modena, Emilia-Romagna 41124, Italy
  • GSK Investigational Site
    Genova, Liguria 16132, Italy
  • GSK Investigational Site
    Pavia, Lombardia 27100, Italy
  • GSK Investigational Site
    Mestre, Veneto 30174, Italy

Showing the first 100 of 168 sites across 14 countries.

08

References and documents

Publications

  • Johansen KL, Cobitz AR, Singh AK, Macdougall IC, Lopes RD, Obrador GT, Kovesdy CP, Israni R, Jha V, Okoro T, Sprys M, Jolly S, Lindsay AC, Bhatt P, Camejo RR, Keeley T, Cizman B, Wheeler DC. The ASCEND-NHQ randomized trial found positive effects of daprodustat on hemoglobin and quality of life in patients with non-dialysis chronic kidney disease. Kidney Int. 2023 Jun;103(6):1180-1192. doi: 10.1016/j.kint.2023.02.019. Epub 2023 Mar 2. PubMed 36868377 ↗
  • Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2. PubMed 36005278 ↗

Study documents

  • Study protocol · Aug 23, 2019
  • Statistical analysis plan · Nov 12, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Supporting information: Study protocol, Sap, Icf, Csr

09

Registry details

Key details

Study ID
NCT03409107
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Jan 24, 2018
Start date
Mar 5, 2018
Primary completion
Oct 7, 2020
Completion
Oct 7, 2020
Results posted
Nov 3, 2021
Last update
Apr 2, 2024

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Kidney Diseases→

Other studies from this sponsor

GlaxoSmithKline

Start the discussion