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)
Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT03409107
Collaborator
(none)
614
168
2
31.1
3.7
0.1
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
614 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Participants will be randomized to receive Daprodustat or placebo in a randomized manner.Participants will be randomized to receive Daprodustat or placebo in a randomized manner.
Masking:
Double (Participant, Investigator)
Masking Description:
This will be a double-blind study. The participant, investigator, site staff, and study team will be blinded to the assigned study treatment.
Primary Purpose:
Treatment
Official Title:
A 28-week, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-center, Study in Recombinant Human Erythropoietin (rhEPO) naïve Non-dialysis Participants With Anemia Associated With Chronic Kidney Disease to Evaluate the Efficacy, Safety and Effects on Quality of Life of Daprodustat Compared to Placebo
Actual Study Start Date
:
Mar 5, 2018
Actual Primary Completion Date
:
Oct 7, 2020
Actual Study Completion Date
:
Oct 7, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Daprodustat receivers Participants will receive oral daprodustat once daily |
Drug: Daprodustat (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.
Drug: Iron therapy
Iron therapy will be administered if ferritin is <50 Nano gram per milliliter and/or TSAT is <15 percent.
|
| Placebo Comparator: Placebo receivers Participants will receive oral placebo once daily |
Drug: Placebo
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.
Drug: Iron therapy
Iron therapy will be administered if ferritin is <50 Nano gram per milliliter and/or TSAT is <15 percent.
|
Outcome Measures
Primary Outcome Measures
- Mean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28) [Baseline (Day 1) and Week 24 to Week 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.
Secondary Outcome Measures
- Percentage of Participants With Hemoglobin Increase of >=1.0 Grams Per Deciliter From Baseline to Evaluation Period [Baseline (Day 1) and Week 24 to Week 28]
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.
- Change From Baseline in Short Form-36 (SF-36) Questionnaire Vitality Domain Score by Traditional Scoring at Week 28 [Baseline (Day 1) and 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.
- Percentage of Participants With Hgb Response (Hgb in the 11-12 Grams/Deciliter Range) During Evaluation Period (Week 24 to Week 28 Inclusive) [Week 24 to Week 28]
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.
- 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) [Week 24 to Week 28]
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'.
- 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) [Week 24 to Week 28]
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'
- Change From Baseline in Post-randomization Hgb at Week 28 [Baseline (Day 1) and 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.
- Rate of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria [Up to Week 28]
The incidence rate of participants permanently stopping randomized treatment due to meeting rescue criteria is presented.
- Change From Baseline by Domain and Single Item Scores on the Chronic Kidney Disease -Anemia Questionnaire (CKD-AQ) Symptom Questionnaire [Baseline (Day 1) and Week 28]
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.
- Change From Baseline in Patient Global Impression of Severity (PGI-S) [Baseline (Day 1) and Week 28]
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.
- Change From Baseline in the SF-36 Physical Functioning Domain [Baseline (Day 1) and 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 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.
- Change From Baseline of the SF-36 Individual Items in the Vitality Domain [Baseline (Day 1) and 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 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.
- Number of Participants Currently Employed as Per Work Productivity and Activity Impairment Questionnaire: Anemic Symptoms Clinical Practice Version (WPAI-ANS-CPV) [Week 8, Week 12 and Week 28]
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.
- Change From Baseline in WPAI-ANS-CPV: Percent Time Missed From Work [Baseline (Day 1), Week 8, Week 12 and Week 28]
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.
- Change From Baseline in WPAI-ANS-CPV: Mean Hours Missed From Work in the Past 7 Days [Baseline (Day 1), Week 8, Week 12 and Week 28]
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.
- Change From Baseline in WPAI: Percent Impairment at Work [Baseline (Day 1), Week 8, Week 12 and Week 28]
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.
- Change From Baseline in WPAI: Percent Overall Work Impairment [Baseline (Day 1), Week 8, Week 12 and Week 28]
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.
- Change From Baseline in WPAI: Percent Regular Daily Activity Impairment [Baseline (Day 1), Week 8, Week 12 and Week 28]
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.
- Change From Baseline in EuroQol 5 Dimension 5 Level Health Utility Index (EQ-5D-5L) Utility Score [Baseline (Day 1) and Week 28]
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.
- Change From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score [Baseline (Day 1) and Week 28]
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.
- Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP) at Week 28 [Baseline (Day 1) and 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.
- Percentage of Participants With at Least One Blood Pressure (BP) Exacerbation Event [Up to Week 28]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
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:
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Homewood | Alabama | United States | 35209 |
| 2 | GSK Investigational Site | Little Rock | Arkansas | United States | 72204 |
| 3 | GSK Investigational Site | Downey | California | United States | 90242 |
| 4 | GSK Investigational Site | Fresno | California | United States | 93720 |
| 5 | GSK Investigational Site | Lynwood | California | United States | 90262 |
| 6 | GSK Investigational Site | Northridge | California | United States | 91324 |
| 7 | GSK Investigational Site | Northridge | California | United States | 91325 |
| 8 | GSK Investigational Site | Riverside | California | United States | 82503 |
| 9 | GSK Investigational Site | Salinas | California | United States | 93901 |
| 10 | GSK Investigational Site | Santa Ana | California | United States | 92704 |
| 11 | GSK Investigational Site | Denver | Colorado | United States | 80230 |
| 12 | GSK Investigational Site | Hartford | Connecticut | United States | 06112 |
| 13 | GSK Investigational Site | Middlebury | Connecticut | United States | 06762 |
| 14 | GSK Investigational Site | Coral Springs | Florida | United States | 33067 |
| 15 | GSK Investigational Site | Hollywood | Florida | United States | 33024 |
| 16 | GSK Investigational Site | Kissimmee | Florida | United States | 34741 |
| 17 | GSK Investigational Site | Lauderdale Lakes | Florida | United States | 33313 |
| 18 | GSK Investigational Site | Pembroke Pines | Florida | United States | 33028 |
| 19 | GSK Investigational Site | Tampa | Florida | United States | 33614 |
| 20 | GSK Investigational Site | Adairsville | Georgia | United States | 30103 |
| 21 | GSK Investigational Site | Macon | Georgia | United States | 31201 |
| 22 | GSK Investigational Site | Macon | Georgia | United States | 31217 |
| 23 | GSK Investigational Site | Statesboro | Georgia | United States | 30458 |
| 24 | GSK Investigational Site | Indianapolis | Indiana | United States | 46260 |
| 25 | GSK Investigational Site | Overland Park | Kansas | United States | 66210 |
| 26 | GSK Investigational Site | Buckley | Michigan | United States | 49620 |
| 27 | GSK Investigational Site | Detroit | Michigan | United States | 48202 |
| 28 | GSK Investigational Site | Saint Clair Shores | Michigan | United States | 48081 |
| 29 | GSK Investigational Site | Brookhaven | Mississippi | United States | 39601 |
| 30 | GSK Investigational Site | Saint Louis | Missouri | United States | 63136 |
| 31 | GSK Investigational Site | Rochester | New Hampshire | United States | 03867 |
| 32 | GSK Investigational Site | Asheville | North Carolina | United States | 28801 |
| 33 | GSK Investigational Site | Charlotte | North Carolina | United States | 28262 |
| 34 | GSK Investigational Site | Durham | North Carolina | United States | 27704 |
| 35 | GSK Investigational Site | Midwest City | Oklahoma | United States | 73130 |
| 36 | GSK Investigational Site | Oklahoma City | Oklahoma | United States | 73112 |
| 37 | GSK Investigational Site | Beaver | Pennsylvania | United States | 15009 |
| 38 | GSK Investigational Site | Duncansville | Pennsylvania | United States | 16635 |
| 39 | GSK Investigational Site | Scottdale | Pennsylvania | United States | 15683 |
| 40 | GSK Investigational Site | Smithfield | Pennsylvania | United States | 15478 |
| 41 | GSK Investigational Site | West Reading | Pennsylvania | United States | 19611 |
| 42 | GSK Investigational Site | Orangeburg | South Carolina | United States | 29118 |
| 43 | GSK Investigational Site | Kingsport | Tennessee | United States | 37660 |
| 44 | GSK Investigational Site | Memphis | Tennessee | United States | 38163 |
| 45 | GSK Investigational Site | DeSoto | Texas | United States | 75115 |
| 46 | GSK Investigational Site | El Paso | Texas | United States | 79935 |
| 47 | GSK Investigational Site | McAllen | Texas | United States | 78503 |
| 48 | GSK Investigational Site | Waxahachie | Texas | United States | 75165 |
| 49 | GSK Investigational Site | Norfolk | Virginia | United States | 23502 |
| 50 | GSK Investigational Site | Ciudad Autonoma de Buenos Aires | Buenos Aires | Argentina | C1128AAF |
| 51 | GSK Investigational Site | Ciudad Autonoma de Buenos Aires | Buenos Aires | Argentina | C1425AGC |
| 52 | GSK Investigational Site | Mar del Plata | Buenos Aires | Argentina | 7600 |
| 53 | GSK Investigational Site | Mar del Plata | Buenos Aires | Argentina | B7600FZN |
| 54 | GSK Investigational Site | San Nicolas | Buenos Aires | Argentina | B2900DMH |
| 55 | GSK Investigational Site | Cordoba | Córdova | Argentina | 5003 |
| 56 | GSK Investigational Site | Rosario | Santa Fe | Argentina | S2000DEJ |
| 57 | GSK Investigational Site | Santa Fe | Argentina | 3000 | |
| 58 | GSK Investigational Site | Sydney | New South Wales | Australia | 2010 |
| 59 | GSK Investigational Site | Heidelberg | Victoria | Australia | 3084 |
| 60 | GSK Investigational Site | Parkville | Victoria | Australia | 3050 |
| 61 | GSK Investigational Site | Murdoch | Western Australia | Australia | 6150 |
| 62 | GSK Investigational Site | Fitzroy | Australia | 3065 | |
| 63 | GSK Investigational Site | Feira de Santana. | Bahia | Brazil | 44001-584 |
| 64 | GSK Investigational Site | Salvador | Bahia | Brazil | 40415-065 |
| 65 | GSK Investigational Site | Vitoria | Espírito Santo | Brazil | 29055450 |
| 66 | GSK Investigational Site | Ribeirão Preto | São Paulo | Brazil | 14025170 |
| 67 | GSK Investigational Site | Santo André - SP | São Paulo | Brazil | 09080-110 |
| 68 | GSK Investigational Site | Sao Jose do Rio Preto | São Paulo | Brazil | 15015200 |
| 69 | GSK Investigational Site | Sao Jose do Rio Preto | São Paulo | Brazil | 15090-000 |
| 70 | GSK Investigational Site | São Bernardo do Campo | São Paulo | Brazil | 09715090 |
| 71 | GSK Investigational Site | São Paulo | Brazil | 04038002 | |
| 72 | GSK Investigational Site | Victoria | British Columbia | Canada | V8V 4A1 |
| 73 | GSK Investigational Site | Brampton | Ontario | Canada | L6T 0G1 |
| 74 | GSK Investigational Site | Guelph | Ontario | Canada | N1H 1B1 |
| 75 | GSK Investigational Site | Kitchener | Ontario | Canada | N2H 5Z8 |
| 76 | GSK Investigational Site | Ottawa | Ontario | Canada | K1H 1A2 |
| 77 | GSK Investigational Site | Sarnia | Ontario | Canada | N7T 4X3 |
| 78 | GSK Investigational Site | Sudbury | Ontario | Canada | P3A-1W8 |
| 79 | GSK Investigational Site | Toronto | Ontario | Canada | M5B 1W8 |
| 80 | GSK Investigational Site | Toronto | Ontario | Canada | M9N 1N8 |
| 81 | GSK Investigational Site | Toronto | Ontario | Canada | M9V 4B4 |
| 82 | GSK Investigational Site | Montréal | Quebec | Canada | H1M 1B1 |
| 83 | GSK Investigational Site | Quebec city | Quebec | Canada | G2J 0C4 |
| 84 | GSK Investigational Site | St-Charles-Borromée | Quebec | Canada | J6E 2B4 |
| 85 | GSK Investigational Site | Quebec | Canada | G3K 2P8 | |
| 86 | GSK Investigational Site | Grenoble cedex 9 | France | 38043 | |
| 87 | GSK Investigational Site | Le Mans cedex 9 | France | 72037 | |
| 88 | GSK Investigational Site | Marseille cedex 5 | France | 13385 | |
| 89 | GSK Investigational Site | Melun | France | 77000 | |
| 90 | GSK Investigational Site | Mulhouse cedex | France | 68070 | |
| 91 | GSK Investigational Site | Nantes Cedex 1 | France | 44093 | |
| 92 | GSK Investigational Site | Nice Cedex 1 | France | 06001 | |
| 93 | GSK Investigational Site | Saint-Priest en Jarez | France | 42270 | |
| 94 | GSK Investigational Site | Catanzaro | Calabria | Italy | 88100 |
| 95 | GSK Investigational Site | Napoli | Campania | Italy | 80131 |
| 96 | GSK Investigational Site | Bologna | Emilia-Romagna | Italy | 40138 |
| 97 | GSK Investigational Site | Modena | Emilia-Romagna | Italy | 41124 |
| 98 | GSK Investigational Site | Genova | Liguria | Italy | 16132 |
| 99 | GSK Investigational Site | Pavia | Lombardia | Italy | 27100 |
| 100 | GSK Investigational Site | Mestre | Veneto | Italy | 30174 |
| 101 | GSK Investigational Site | Busan | Korea, Republic of | 49201 | |
| 102 | GSK Investigational Site | Busan | Korea, Republic of | 49241 | |
| 103 | GSK Investigational Site | Daegu-si | Korea, Republic of | 42601 | |
| 104 | GSK Investigational Site | Daegu | Korea, Republic of | 42415 | |
| 105 | GSK Investigational Site | Gyeonggi-do | Korea, Republic of | 463-712 | |
| 106 | GSK Investigational Site | Seongnam-si, Gyeonggi-do | Korea, Republic of | 13620 | |
| 107 | GSK Investigational Site | Seoul | Korea, Republic of | 03312 | |
| 108 | GSK Investigational Site | Seoul | Korea, Republic of | 08308 | |
| 109 | GSK Investigational Site | Leon | Guanajuato | Mexico | 37530 |
| 110 | GSK Investigational Site | Guadalajara | Jalisco | Mexico | 44150 |
| 111 | GSK Investigational Site | Monterrey | Nuevo León | Mexico | 64060 |
| 112 | GSK Investigational Site | Boca del Rio | Veracruz | Mexico | 24290 |
| 113 | GSK Investigational Site | Córdoba | Veracruz | Mexico | 94550 |
| 114 | GSK Investigational Site | Merida | Yucatán | Mexico | 97070 |
| 115 | GSK Investigational Site | Guadalajara | Mexico | 44600 | |
| 116 | GSK Investigational Site | Merida | Mexico | 97000 | |
| 117 | GSK Investigational Site | Veracruz | Mexico | 91900 | |
| 118 | GSK Investigational Site | Bialystok | Poland | 15-276 | |
| 119 | GSK Investigational Site | Ciechanow | Poland | 06-400 | |
| 120 | GSK Investigational Site | Krakow | Poland | 30510 | |
| 121 | GSK Investigational Site | Krakow | Poland | 31-513 | |
| 122 | GSK Investigational Site | Krakow | Poland | 31-559 | |
| 123 | GSK Investigational Site | Lodz | Poland | 92-213 | |
| 124 | GSK Investigational Site | Lublin | Poland | 20-064 | |
| 125 | GSK Investigational Site | Olawa | Poland | 55-200 | |
| 126 | GSK Investigational Site | Pleszew | Poland | 63-300 | |
| 127 | GSK Investigational Site | Sosnowiec | Poland | 41-200 | |
| 128 | GSK Investigational Site | Swidnik | Poland | 21-040 | |
| 129 | GSK Investigational Site | Szczecin | Poland | 70-111 | |
| 130 | GSK Investigational Site | Tczew | Poland | 83-110 | |
| 131 | GSK Investigational Site | Warszawa | Poland | 01-868 | |
| 132 | GSK Investigational Site | Warszawa | Poland | 02-801 | |
| 133 | GSK Investigational Site | Warszawa | Poland | 04-749 | |
| 134 | GSK Investigational Site | Brasov | Romania | 500283 | |
| 135 | GSK Investigational Site | Bucharest | Romania | 022328 | |
| 136 | GSK Investigational Site | Bucharest | Romania | 042122 | |
| 137 | GSK Investigational Site | Cluj-Napoca | Romania | 400139 | |
| 138 | GSK Investigational Site | Craiova | Romania | 200642 | |
| 139 | GSK Investigational Site | Deva | Romania | 330084 | |
| 140 | GSK Investigational Site | Oradea | Romania | 410469 | |
| 141 | GSK Investigational Site | Targu Mures | Romania | 540096 | |
| 142 | GSK Investigational Site | Timisoara | Romania | 300723 | |
| 143 | GSK Investigational Site | Izhevsk | Russian Federation | 426061 | |
| 144 | GSK Investigational Site | Kaliningrad | Russian Federation | 236016 | |
| 145 | GSK Investigational Site | Kemerovo | Russian Federation | 650066 | |
| 146 | GSK Investigational Site | Krasnoyarsk | Russian Federation | 660022 | |
| 147 | GSK Investigational Site | Moscow | Russian Federation | 121359 | |
| 148 | GSK Investigational Site | Nizhniy Novgorod | Russian Federation | 603126 | |
| 149 | GSK Investigational Site | Pyatigorsk | Russian Federation | 357500 | |
| 150 | GSK Investigational Site | Pyatigorsk | Russian Federation | 357538 | |
| 151 | GSK Investigational Site | Rostov-on-Don | Russian Federation | 344022 | |
| 152 | GSK Investigational Site | Ryazan | Russian Federation | 390037 | |
| 153 | GSK Investigational Site | Saint Petersburg | Russian Federation | 194355 | |
| 154 | GSK Investigational Site | Saint Petersburg | Russian Federation | 197022 | |
| 155 | GSK Investigational Site | Stavropol | Russian Federation | 355017 | |
| 156 | GSK Investigational Site | Yaroslavl | Russian Federation | 150000 | |
| 157 | GSK Investigational Site | Yaroslavl | Russian Federation | 150030 | |
| 158 | GSK Investigational Site | Yaroslavl | Russian Federation | 150062 | |
| 159 | GSK Investigational Site | Badalona | Spain | 08916 | |
| 160 | GSK Investigational Site | Madrid | Spain | 28040 | |
| 161 | GSK Investigational Site | Santiago de Compostela | Spain | 15890 | |
| 162 | GSK Investigational Site | Canterbury | Kent | United Kingdom | CT1 3NG |
| 163 | GSK Investigational Site | Derby | United Kingdom | DE22 3NE | |
| 164 | GSK Investigational Site | London | United Kingdom | SE5 9RS | |
| 165 | GSK Investigational Site | Peterborough | United Kingdom | PE3 9GZ | |
| 166 | GSK Investigational Site | Plymouth | United Kingdom | PL6 8DH | |
| 167 | GSK Investigational Site | Shrewsbury | United Kingdom | SY3 8XQ | |
| 168 | GSK Investigational Site | Swansea | United Kingdom | SA6 6NL |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT03409107
Other Study ID Numbers:
- 205270
- 2017-002270-39
First Posted:
Jan 24, 2018
Last Update Posted:
Nov 3, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This was a multicenter study conducted at 142 centers in 14 countries. Participants were randomized to receive either Daprodustat or Placebo. |
|---|---|
| Pre-assignment Detail | A total of 1336 participants were screened, of which 722 were screen failures. A total of 614 participants were enrolled in the study. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Period Title: Overall Study | ||
| STARTED | 307 | 307 |
| COMPLETED | 290 | 300 |
| NOT COMPLETED | 17 | 7 |
Baseline Characteristics
| Arm/Group Title | Placebo | Daprodustat | Total |
|---|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) | Total of all reporting groups |
| Overall Participants | 307 | 307 | 614 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
66.6
(12.93)
|
65.3
(13.43)
|
65.9
(13.19)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
178
58%
|
176
57.3%
|
354
57.7%
|
| Male |
129
42%
|
131
42.7%
|
260
42.3%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| AMERICAN INDIAN OR ALASKA NATIVE |
34
11.1%
|
34
11.1%
|
68
11.1%
|
| ASIAN: CENTRAL/SOUTH ASIAN HERITAGE |
3
1%
|
6
2%
|
9
1.5%
|
| ASIAN: JAPANESE/EASTASIAN/SOUTHEAST ASIAN HERITAGE |
24
7.8%
|
24
7.8%
|
48
7.8%
|
| ASIAN: MIXED ASIAN RACE |
1
0.3%
|
0
0%
|
1
0.2%
|
| BLACK OR AFRICAN AMERICAN |
47
15.3%
|
44
14.3%
|
91
14.8%
|
| NATIVE HAWAIIAN/OTHER PACIFIC ISLANDER |
1
0.3%
|
0
0%
|
1
0.2%
|
| WHITE |
195
63.5%
|
197
64.2%
|
392
63.8%
|
| BLACK OR AFRICAN AMERICAN AND WHITE |
2
0.7%
|
2
0.7%
|
4
0.7%
|
Outcome Measures
| Title | Mean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Population comprised all randomized participants regardless of whether they took study drug. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 307 | 307 |
| Least Squares Mean (Standard Error) [Grams per deciliter] |
0.19
(0.062)
|
1.58
(0.061)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | One-sided p-value based on test of null hypothesis: (Daprodustat - Placebo) <= 0 versus alternative: difference > 0. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 1.40 | |
| Confidence Interval |
(2-Sided) 95% 1.23 to 1.56 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment group comparisons were based on a ANCOVA model with terms for treatment, Baseline hemoglobin, and region. | |
| Title | Percentage of Participants With Hemoglobin Increase of >=1.0 Grams Per Deciliter From Baseline to Evaluation Period |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 307 | 307 |
| Number [Percentage of participants] |
18
5.9%
|
77
25.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat - Placebo) <=0 versus alternative: difference > 0 | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Response rate |
| Estimated Value | 0.56 | |
| Confidence Interval |
(2-Sided) 95% 0.49 to 0.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment group comparisons were based on a Cochran-Mantel-Haenszel test adjusted for treatment group and region. | |
| Title | Change From Baseline in Short Form-36 (SF-36) Questionnaire Vitality Domain Score by Traditional Scoring at Week 28 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 307 | 307 |
| Least Squares Mean (Standard Error) [Scores on a scale] |
1.93
(1.161)
|
7.29
(1.121)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | One-sided p-value based on test of null hypothesis:(Daprodustat-Placebo) <= 0 vs alternative: difference > 0. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 5.36 | |
| Confidence Interval |
(2-Sided) 95% 2.17 to 8.56 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment group comparisons were based on ANCOVA model with terms for treatment, Baseline score, and region. | |
| Title | Percentage of Participants With Hgb Response (Hgb in the 11-12 Grams/Deciliter Range) During Evaluation Period (Week 24 to Week 28 Inclusive) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 307 | 307 |
| Number [Percentage of participants] |
8
2.6%
|
52
16.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus alternative: difference >0. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Response rate |
| Estimated Value | 0.45 | |
| Confidence Interval |
(2-Sided) 95% 0.37 to 0.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment group comparisons are based on a Cochran-Mantel-Haenszel test adjusted for treatment group, and region | |
| Title | 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) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 216 | 252 |
| Median (Full Range) [Percentage of days] |
0.00
|
53.59
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in treatment effect |
| Estimated Value | 38.80 | |
| Confidence Interval |
(2-Sided) 95% 25.00 to 54.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 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) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 216 | 252 |
| Median (Full Range) [Percentage of days] |
0.00
|
53.59
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | One-sided superiority p-value from the van Elteren test | |
| Method | van Elteren test | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in treatment effect |
| Estimated Value | 0.768 | |
| Confidence Interval |
(2-Sided) 95% 0.729 to 0.806 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Mann-Whitney estimate of the treatment difference stratified by region has been presented. | |
| Title | Change From Baseline in Post-randomization Hgb at Week 28 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 301 | 299 |
| Least Squares Mean (Standard Error) [Grams per deciliter] |
0.20
(0.070)
|
1.56
(0.069)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | One-sided superiority p-value from the MMRM model | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | 1.36 | |
| Confidence Interval |
(2-Sided) 95% 1.16 to 1.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment 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. | |
| Title | Rate of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria |
|---|---|
| Description | The incidence rate of participants permanently stopping randomized treatment due to meeting rescue criteria is presented. |
| Time Frame | Up to Week 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 307 | 307 |
| Number (95% Confidence Interval) [Events per 100 person year] |
18.88
|
1.33
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | One-sided p-value was based on Wald test of null hypothesis: (Daprodustat/Placebo) >=1 versus alternative: ratio<1. | |
| Method | Wald test | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.07 | |
| Confidence Interval |
(2-Sided) 95% 0.02 to 0.30 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio was estimated using a Cox proportional hazard regression model adjusted for treatment group and region. | |
| Title | Change From Baseline by Domain and Single Item Scores on the Chronic Kidney Disease -Anemia Questionnaire (CKD-AQ) Symptom Questionnaire |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 193 | 212 |
| Tired/Low Energy/Weak Domain |
2.81
(1.132)
|
8.72
(1.086)
|
| Chest Pain/Shortness of Breath Domain |
0.62
(0.971)
|
3.55
(0.932)
|
| Cognitive Domain |
0.48
(1.042)
|
4.27
(0.999)
|
| Difficulty in Sleeping |
2.61
(1.643)
|
5.22
(1.577)
|
| Difficulty Standing for Long Periods of Time |
1.55
(1.630)
|
6.19
(1.563)
|
| Severity-Shortness of Breath, Sitting/Resting |
0.43
(0.995)
|
3.11
(0.954)
|
| Time with Shortness of BreathnotDoingActivity |
0.29
(1.083)
|
2.30
(1.037)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 5.91 | |
| Confidence Interval |
(2-Sided) 95% 2.83 to 9.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Analysis 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. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0152 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 2.93 | |
| Confidence Interval |
(2-Sided) 95% 0.28 to 5.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Analysis 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. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0045 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 3.79 | |
| Confidence Interval |
(2-Sided) 95% 0.95 to 6.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Analysis 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. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1267 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 2.61 | |
| Confidence Interval |
(2-Sided) 95% -1.87 to 7.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Analysis 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 | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0203 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 4.64 | |
| Confidence Interval |
(2-Sided) 95% 0.20 to 9.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Analysis 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 | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0266 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 2.68 | |
| Confidence Interval |
(2-Sided) 95% -0.04 to 5.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Analysis 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 | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0907 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 2.01 | |
| Confidence Interval |
(2-Sided) 95% -0.94 to 4.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Analysis 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 | |
| Title | Change From Baseline in Patient Global Impression of Severity (PGI-S) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 193 | 212 |
| Least Squares Mean (Standard Error) [Scores on a scale] |
-0.04
(0.055)
|
-0.18
(0.052)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0391 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat-rhEPO) >=0 versus alternative: difference <0 | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -0.13 | |
| Confidence Interval |
(2-Sided) 95% -0.28 to 0.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | MMRM 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. | |
| Title | Change From Baseline in the SF-36 Physical Functioning Domain |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 190 | 210 |
| Least Squares Mean (Standard Error) [Scores on a scale] |
1.23
(1.354)
|
3.80
(1.298)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0858 |
| Comments | One sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) <=0 vs. alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 2.57 | |
| Confidence Interval |
(2-Sided) 95% -1.12 to 6.26 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | MMRM 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. | |
| Title | Change From Baseline of the SF-36 Individual Items in the Vitality Domain |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 190 | 210 |
| Did you feel full of life? |
-0.02
(0.070)
|
0.16
(0.067)
|
| Did you have a lot of energy? |
0.09
(0.066)
|
0.26
(0.063)
|
| Did you feel worn out? |
0.16
(0.067)
|
0.34
(0.064)
|
| Did you feel tired? |
0.08
(0.060)
|
0.34
(0.057)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0357 |
| Comments | One sided p-value based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.17 | |
| Confidence Interval |
(2-Sided) 95% -0.02 to 0.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | MMRM 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?. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0328 |
| Comments | One-sided p-value based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.17 | |
| Confidence Interval |
(2-Sided) 95% -0.01 to 0.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | MMRM 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?. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0252 |
| Comments | One-sided p-value based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.18 | |
| Confidence Interval |
(2-Sided) 95% 0.00 to 0.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | MMRM 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?. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0010 |
| Comments | One-sided p-value based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.26 | |
| Confidence Interval |
(2-Sided) 95% 0.10 to 0.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | MMRM 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?. | |
| Title | Number of Participants Currently Employed as Per Work Productivity and Activity Impairment Questionnaire: Anemic Symptoms Clinical Practice Version (WPAI-ANS-CPV) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in category titles). |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 249 | 251 |
| Week 8, No, n=249, 250 |
195
63.5%
|
204
66.4%
|
| Week 8, Yes, n=249, 250 |
54
17.6%
|
46
15%
|
| Week 12, No, n=234, 251 |
183
59.6%
|
212
69.1%
|
| Week 12, Yes, n=234, 251 |
51
16.6%
|
39
12.7%
|
| Week 28, No, n=193, 213 |
158
51.5%
|
178
58%
|
| Week 28, Yes, n=193, 213 |
35
11.4%
|
35
11.4%
|
| Title | Change From Baseline in WPAI-ANS-CPV: Percent Time Missed From Work |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in category titles). |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 50 | 39 |
| Week 8, n=50, 39 |
-2.4
(28.40)
|
-6.1
(24.92)
|
| Week 12, n=46, 31 |
0.9
(28.79)
|
4.2
(27.96)
|
| Week 28, n=28, 25 |
0.0
(33.59)
|
0.3
(31.01)
|
| Title | Change From Baseline in WPAI-ANS-CPV: Mean Hours Missed From Work in the Past 7 Days |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at indicated time points are presented (presented by n=X in category titles). |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 50 | 39 |
| Week 8, n=50, 39 |
0.1
(18.46)
|
-1.8
(11.88)
|
| Week 12, n=46, 31 |
1.4
(14.07)
|
2.4
(16.83)
|
| Week 28, n=28, 25 |
0.3
(19.90)
|
1.0
(14.24)
|
| Title | Change From Baseline in WPAI: Percent Impairment at Work |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in category titles). |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 45 | 32 |
| 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)
|
| Title | Change From Baseline in WPAI: Percent Overall Work Impairment |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in category titles). |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 45 | 32 |
| Week 8, n=45, 32 |
-4.3
(24.04)
|
-12.0
(25.90)
|
| Week 12, n=41, 26 |
0.5
(25.81)
|
-3.2
(33.35)
|
| Week 28, n=24, 20 |
-9.3
(37.45)
|
-8.4
(19.12)
|
| Title | Change From Baseline in WPAI: Percent Regular Daily Activity Impairment |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in category titles). |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 246 | 248 |
| 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)
|
| Title | Change From Baseline in EuroQol 5 Dimension 5 Level Health Utility Index (EQ-5D-5L) Utility Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at indicated time points are presented. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 106 | 116 |
| Least Squares Mean (Standard Error) [Scores on a scale] |
0.01
(0.015)
|
0.03
(0.014)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1098 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) <=0 versus. alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.03 | |
| Confidence Interval |
(2-Sided) 95% -0.02 to 0.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Based 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. | |
| Title | Change From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 106 | 116 |
| Least Squares Mean (Standard Error) [Scores on a scale] |
0.80
(1.427)
|
5.30
(1.373)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0120 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat-Placebo) <=0 vs. alternative: difference >0. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 4.50 | |
| Confidence Interval |
(2-Sided) 95% 0.60 to 8.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 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. | |
| Title | Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP) at Week 28 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 202 | 230 |
| SBP |
-0.63
(1.045)
|
-0.23
(0.981)
|
| DBP |
-0.96
(0.625)
|
0.84
(0.587)
|
| MAP |
-0.82
(0.674)
|
0.49
(0.632)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6106 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat - Placebo) >= 0 versus alternative: difference <0 | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.40 | |
| Confidence Interval |
(2-Sided) 95% -2.42 to 3.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | MMRM 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. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9819 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat - Placebo) >= 0 versus alternative: difference < 0 | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 1.80 | |
| Confidence Interval |
(2-Sided) 95% 0.12 to 3.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | MMRM 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. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9215 |
| Comments | One-sided p-value was based on test of null hypothesis: (Daprodustat - Placebo) >= 0 versus alternative: difference <0 | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 1.31 | |
| Confidence Interval |
(2-Sided) 95% -0.51 to 3.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | MMRM 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. | |
| Title | Percentage of Participants With at Least One Blood Pressure (BP) Exacerbation Event |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population. |
| Arm/Group Title | Placebo | Daprodustat |
|---|---|---|
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) |
| Measure Participants | 307 | 307 |
| Number [Percentage of participants] |
26
8.5%
|
32
10.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Daprodustat |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0680 |
| Comments | One-sided p-value based on test of null hypothesis: (Daprodustat - Placebo) <= 0 versus alternative: difference > 0. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Response rate |
| Estimated Value | 0.06 | |
| Confidence Interval |
(2-Sided) 95% -0.02 to 0.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cochran-Mantel-Haenszel test was performed for treatment group comparison. | |
Adverse Events
| Time Frame | All cause mortality, serious adverse events (SAEs) and non-serious AEs were collected up to follow-up (Week 32). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Population comprised of all randomized participants who received at least 1 dose of study treatment. Treatment emergent non-serious adverse events and serious adverse events are reported. One participant who was randomized to placebo accidently received daprodustat during the study and therefore was evaluated in the daprodustat treatment group for the safety outcomes | |||
| Arm/Group Title | Placebo | Daprodustat | ||
| Arm/Group Description | Participants received matching placebo once daily orally for up to 28 weeks followed by 4 weeks of follow-up. | Participants received daprodustat tablets with titrated dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 milligrams (mg) once daily orally for up to 28 weeks, followed by 4 weeks of follow-up. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (11 to 12 grams per deciliter [g/dL]) | ||
All Cause Mortality |
||||
| Placebo | Daprodustat | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/306 (5.2%) | 10/308 (3.2%) | ||
Serious Adverse Events |
||||
| Placebo | Daprodustat | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 68/306 (22.2%) | 62/308 (20.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 8/306 (2.6%) | 9 | 2/308 (0.6%) | 2 |
| Cardiac disorders | ||||
| Cardiac failure congestive | 2/306 (0.7%) | 2 | 3/308 (1%) | 4 |
| Cardiac failure acute | 4/306 (1.3%) | 4 | 0/308 (0%) | 0 |
| Acute coronary syndrome | 2/306 (0.7%) | 2 | 1/308 (0.3%) | 1 |
| Atrial fibrillation | 0/306 (0%) | 0 | 3/308 (1%) | 3 |
| Bradycardia | 2/306 (0.7%) | 2 | 0/308 (0%) | 0 |
| Left ventricular failure | 0/306 (0%) | 0 | 2/308 (0.6%) | 2 |
| Acute myocardial infarction | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Angina pectoris | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Angina unstable | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Arrhythmia | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Atrial flutter | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Atrial thrombosis | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Cardiac failure chronic | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Coronary artery disease | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Mitral valve incompetence | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Myocardial infarction | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Myocardial ischaemia | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Right ventricular failure | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Cardiac failure | 1/306 (0.3%) | 1 | 4/308 (1.3%) | 4 |
| Tricuspid valve incompetence | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Ear and labyrinth disorders | ||||
| Hypoacusis | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Tympanic membrane perforation | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Vertigo positional | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Eye disorders | ||||
| Ulcerative keratitis | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Vitreous haemorrhage | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Gastrointestinal haemorrhage | 2/306 (0.7%) | 2 | 1/308 (0.3%) | 1 |
| Vomiting | 1/306 (0.3%) | 1 | 2/308 (0.6%) | 2 |
| Constipation | 2/306 (0.7%) | 2 | 0/308 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 1/306 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Abdominal pain upper | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Ascites | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Colitis | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Diabetic gastropathy | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Diarrhoea | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Large intestine polyp | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Nausea | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| General disorders | ||||
| Death | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| General physical health deterioration | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Autoimmune hepatitis | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Cholangitis | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Cholelithiasis | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Infections and infestations | ||||
| Sepsis | 2/306 (0.7%) | 2 | 2/308 (0.6%) | 2 |
| Cellulitis | 2/306 (0.7%) | 2 | 1/308 (0.3%) | 1 |
| Urinary tract infection | 4/306 (1.3%) | 5 | 2/308 (0.6%) | 2 |
| Pneumonia | 1/306 (0.3%) | 1 | 2/308 (0.6%) | 2 |
| Septic shock | 2/306 (0.7%) | 2 | 0/308 (0%) | 0 |
| Urosepsis | 0/306 (0%) | 0 | 2/308 (0.6%) | 2 |
| COVID-19 | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Diabetic foot infection | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Ear infection | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Endophthalmitis | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Escherichia urinary tract infection | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Gastroenteritis | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Lower respiratory tract infection | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Otitis externa | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Perirectal abscess | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Pneumonia bacterial | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Pyelonephritis | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Upper respiratory tract infection | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Femur fracture | 0/306 (0%) | 0 | 2/308 (0.6%) | 2 |
| Cervical vertebral fracture | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Craniocerebral injury | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Humerus fracture | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Kidney rupture | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Ligament sprain | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Subdural haematoma | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Transplant dysfunction | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Upper limb fracture | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Vascular pseudoaneurysm | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Investigations | ||||
| Blood pressure increased | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Hepatic enzyme increased | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Liver function test abnormal | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Hypoglycaemia | 1/306 (0.3%) | 1 | 2/308 (0.6%) | 2 |
| Fluid overload | 1/306 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Dehydration | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Diabetic ketoacidosis | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Hyperglycaemia | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Hyperkalaemia | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Hyponatraemia | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Atlantoaxial instability | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Osteoarthritis | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Breast cancer | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Pituitary tumour benign | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Plasma cell myeloma | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Nervous system disorders | ||||
| Syncope | 0/306 (0%) | 0 | 3/308 (1%) | 3 |
| Autonomic nervous system imbalance | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Encephalopathy | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Ischaemic stroke | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Sciatica | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Psychiatric disorders | ||||
| Bipolar disorder | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 5/306 (1.6%) | 5 | 5/308 (1.6%) | 6 |
| Renal failure | 6/306 (2%) | 6 | 2/308 (0.6%) | 2 |
| End stage renal disease | 2/306 (0.7%) | 2 | 2/308 (0.6%) | 2 |
| Renal impairment | 2/306 (0.7%) | 3 | 1/308 (0.3%) | 1 |
| Azotaemia | 1/306 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Urinary retention | 2/306 (0.7%) | 2 | 0/308 (0%) | 0 |
| Chronic kidney disease | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| IgA nephropathy | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Nephrolithiasis | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Nephropathy toxic | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Nephrotic syndrome | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Renal haematoma | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 1/306 (0.3%) | 1 | 3/308 (1%) | 3 |
| Pulmonary oedema | 1/306 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Acute interstitial pneumonitis | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Bronchial hyperreactivity | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Chronic obstructive pulmonary disease | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Interstitial lung disease | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Pleural effusion | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Pulmonary hypertension | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Skin ulcer | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Vascular disorders | ||||
| Hypertension | 2/306 (0.7%) | 2 | 2/308 (0.6%) | 2 |
| Hypotension | 3/306 (1%) | 3 | 0/308 (0%) | 0 |
| Hypertensive crisis | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Hypertensive emergency | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Hypovolaemic shock | 1/306 (0.3%) | 1 | 0/308 (0%) | 0 |
| Peripheral arterial occlusive disease | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
| Thrombophlebitis superficial | 0/306 (0%) | 0 | 1/308 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Daprodustat | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 44/306 (14.4%) | 49/308 (15.9%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 17/306 (5.6%) | 22 | 24/308 (7.8%) | 26 |
| General disorders | ||||
| Oedema peripheral | 21/306 (6.9%) | 23 | 12/308 (3.9%) | 14 |
| Vascular disorders | ||||
| Hypertension | 14/306 (4.6%) | 14 | 21/308 (6.8%) | 27 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
| GSKClinicalSupportHD@gsk.com |
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT03409107
Other Study ID Numbers:
- 205270
- 2017-002270-39
First Posted:
Jan 24, 2018
Last Update Posted:
Nov 3, 2021
Last Verified:
Oct 1, 2021