A Phase 2 interventional study of Daprodustat and Darbepoetin alfa in Anaemia, sponsored by GlaxoSmithKline. Terminated at 3 sites in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-27.
Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment
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Among 30 studies testing GSK1278863 in Anemia — 1 open to participants now, 1 under way, 1 of them phase 3. GSK1278863 · Anemia.
Among the 30 studies testing GSK1278863 in Anemia, this one is the 28th largest by enrollment, is one of 2 that started in 2019, is one of 10 in phase 2, and was the 24th registered.
1,810 studies on the registry are indexed under Anemia; 215 are open to participants now.
Browse Anemia studies →1 of the 30 studies testing GSK1278863 in Anemia is open now. Recruiting first, the newest first:
GSK1278863: first FDA approval 2023 (JESDUVROQ). What it is approved for, and how studies give it, is on its page →
Of the 122 Anemia studies recruiting now, 67 (55%) set no upper age limit and 37 (30%) stop at 75 or younger; 34 take children under 18; 23 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
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30 studies; the count open now beside each. This study's row is marked.
First in 2010; this study’s year is marked. 2 started in 2019.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 6 is below the median of 117 across 1,336 interventional studies indexed under Anemia.
Median enrollment 76 across the 30 interventional studies. Of the 29 that completed or were terminated, 23 (79%) have results posted.
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29 of 30 have an industry lead sponsor. The 3 most frequent:
GlaxoSmithKline is the lead sponsor of 3,650 studies on the registry; 117 are open to participants now.
Of its 265 completed or terminated interventional studies of FDA-regulated products, 241 (91%) have results posted.
35 studies in Anemia by GlaxoSmithKline: none open now, none under way, none of them phase 3. Of 35 finished, 25 (71%) have results posted.
Among the 35 studies in Anemia by GlaxoSmithKline, this one is the 33rd largest by enrollment, is one of 2 that started in 2019, is one of 11 in phase 2, and was the 30th registered.
GlaxoSmithKline’s Anemia studies by the year they started, since 2006.
1 of the studies testing GSK1278863 in Anemia that are under way reach primary completion within a year, 1 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT07300111Phase 3Qilu Pharmaceutical Co., Ltd.A Study to Evaluate Efficacy and Safety of QLG1218(Daprodustat) in Chinese Hemodialysis (HD)-Dependent Subjects With Anemia Associated With Chronic Kidney Disease (CKD) | 2027-05 |
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Among the 30 studies testing GSK1278863 in Anemia, from their registry updates:
Nothing recorded among them since 2026-09-25.
Among GlaxoSmithKline’s 35 in Anemia:
Nothing recorded among them since 2026-09-25.
This tab as a report to print or save as PDF → With an account.
Daprodustat has demonstrated an ability to effectively raise hemoglobin concentrations with lower erythropoietin (EPO) levels than those observed after administration of recombinant human erythropoietin (rhEPOs). Therefore, daprodustat has the potential to treat anemia of chronic kidney disease (CKD) with a lower cardiovascular (CV) risk than is observed with the rhEPOs. While the effect of rhEPOs on endothelial function has been assessed, to date the effect of daprodustat or other prolyl hydroxylase inhibitor (PHI) compounds on endothelial function has not. Therefore, the purpose of this study is to compare the effect of daprodustat to darbepoetin alfa on endothelial function by assessing FBF in participants with anemia of CKD by using venous occlusion plethysmography as a means to estimate the potential for daprodustat to have a lower risk of CV events as compared to rhEPO.
This study will use a randomized, repeat dose, open label, parallel group design, in adult, not on-dialysis, male and female participants with anemia of CKD that are currently not treated with rhEPOs.
The study will comprise of three study periods: a screening period starting up to 30 days prior to Day 1, a 42 day (6 week) treatment period, and a follow-up visit up to 14 days later. The total duration of participants involvement is up to 14 weeks (including screening and follow up visit). Approximately 50 participants will be randomized to either daprodustat or darbepoetin alfa.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive 2 milligram (mg) daprodustat tablets once daily via oral route for a period of 41 days.
Drug: Daprodustat · Drug: Acetylcholine · Drug: Sodium nitroprusside · Drug: L-N-monomethyl arginine acetate (L-NMMA)
Participants will receive Darbepoetin alfa solution for injection, administered as a single subcutaneous injection, once every two weeks (Days 1, 14 and 28).
Drug: Darbepoetin alfa · Drug: Acetylcholine · Drug: Sodium nitroprusside · Drug: L-N-monomethyl arginine acetate (L-NMMA)
Daprodustat will be available as 1 mg, 2 mg and 4 mg oral tablets. Daprodustat will be administered once daily by oral route without regard for food.
Darbepoetin alfa will be given as solution for injection for subcutaneous administration every 2 weeks.
Acetylcholine will be used as a challenge agent and will be infused at 7.5, 15 and 30 micrograms/minute each for 6 minutes per infusion into the brachial artery of the test arm.
Sodium nitroprusside will be used as a challenge agent and will be infused at 3 and 10 micrograms/minute each for 6 minutes per infusion into the brachial artery of the test arm.
L-N-monomethyl arginine acetate will be used as a challenge agent and will be infused at a doses of 2 and 8 micromoles/minute for 6 minutes into the brachial artery of the test arm.
Change in FBF Ratio in Response to Acetylcholine (Day 1 to Day 42)
Venous occlusion plethysmography was used for FBF assessment. Acetylcholine (ACH) was infused intra-arterially at 7.5, 15 and 30 micrograms/minute (ug/min) each for 6 minutes per infusion. FBF ratio was defined as the ratio of a participant's treatment (infused) arm value divided by the non-treatment (non-infused) arm value. The overall ratio was determined by taking the participant's Day 42 FBF ratio and dividing by the Day 1 FBF ratio.
Time frame: Day 1 to Day 42
Change in the Absolute FBF From Day 1 to Day 42 in Response to Acetylcholine
Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. Measures were made in both arms concurrently. Change in the absolute FBF from Day 1 to Day 42 in response to acetylcholine is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to acetylcholine.
Time frame: Day 1 to Day 42
Change in FBF Ratio in Response to Sodium Nitroprusside (Day 1 to Day 42)
Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. FBF ratio was defined as the ratio of a participant's treatment (infused) arm value divided by the non-treatment (non-infused) arm value. The overall ratio was determined by taking the participant's Day 42 FBF ratio and dividing by the Day 1 FBF ratio.
Time frame: Day 1 to Day 42
Change in the Absolute FBF From Day 1 to Day 42 in Response to Sodium Nitroprusside
Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF from Day 1 to Day 42 in response to sodium nitroprusside is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to sodium nitroprusside.
Time frame: Day 1 to Day 42
Change in FBF Ratio in Response to NG-monomethyl Arginine Acetate (L-NMMA) (Day 1 to Day 42)
Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 micromoles per minute (umol/min) each infused for 6 minutes into the brachial artery of the test arm. FBF ratio was defined as the ratio of a participant's treatment (infused) arm value divided by the non-treatment (non-infused) arm value. The overall ratio was determined by taking the participant's Day 42 FBF ratio and dividing by the Day 1 FBF ratio.
Time frame: Day 1 to Day 42
Change in the Absolute FBF From Day 1 to Day 42 in Response to L-NMMA
Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF from Day 1 to Day 42 in response to L-NMMA is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to L-NMMA.
Time frame: Day 1 to Day 42
Change in FBF Ratio in Response to Acetylcholine at Day 42 Versus (vs) Day 1 in Participants Treated With Daprodustat
Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio.
Time frame: Day 1 and Day 42
Change in FBF Ratio in Response to Sodium Nitroprusside at Day 42 vs Day 1 in Participants Treated With Daprodustat
Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio.
Time frame: Day 1 and Day 42
Change in FBF Ratio in Response to L-NMMA at Day 42 vs Day 1 in Participants Treated With Daprodustat
Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio.
Time frame: Day 1 and Day 42
Change in FBF Ratio in Response to Acetylcholine at Day 42 vs Day 1 in Participants Treated With Darbepoetin Alfa
Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio.
Time frame: Day 1 and Day 42
Change in FBF Ratio in Response to Sodium Nitroprusside at Day 42 vs Day 1 in Participants Treated With Darbepoetin Alfa
Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio.
Time frame: Day 1 and Day 42
Change in FBF Ratio in Response to L-NMMA at Day 42 vs Day 1 in Participants Treated With Darbepoetin Alfa
Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio.
Time frame: Day 1 and Day 42
Change in the Absolute FBF in Response to Acetylcholine at Day 42 vs Day 1 in Participants Treated With Daprodustat
Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. Measures were made in both arms concurrently. Change in the absolute FBF in response to acetylcholine at Day 42 vs Day1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to acetylcholine in participants treated with daprodustat.
Time frame: Day 1 and Day 42
Change in the Absolute FBF in Response to Sodium Nitroprusside at Day 42 vs Day 1 in Participants Treated With Daprodustat
Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF in response to sodium nitroprusside at Day 42 vs Day 1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to sodium nitroprusside in participants treated with daprodustat.
Time frame: Day 1 and Day 42
Change in the Absolute FBF in Response to L-NMMA at Day 42 vs Day 1 in Participants Treated With Daprodustat
Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF in response to L-NMMA at Day 42 vs Day 1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to L-NMMA in participants treated with daprodustat.
Time frame: Day 1 and Day 42
Change in the Absolute FBF in Response to Acetylcholine at Day 42 vs Day 1 in Participants Treated With Darbepoetin Alfa
Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. Measures were made in both arms concurrently. Change in the absolute FBF in response to acetylcholine at Day 42 vs Day1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to acetylcholine in participants treated with darbepoetin alfa.
Time frame: Day 1 and Day 42
Change in the Absolute FBF in Response to Sodium Nitroprusside at Day 42 vs Day 1 in Participants Treated With Darbepoetin Alfa
Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF in response to sodium nitroprusside at Day 42 vs Day 1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to sodium nitroprusside in participants treated with darbepoetin alfa.
Time frame: Day 1 and Day 42
Change in the Absolute FBF in Response to L-NMMA at Day 42 vs Day 1 in Participants Treated With Darbepoetin Alfa
Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF in response to L-NMMA at Day 42 vs Day 1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to L-NMMA in participants treated with darbepoetin alfa.
Time frame: Day 1 and Day 42
Change in Augmentation Index (AIx) From Day 1 to 42
Pulse wave analysis (PWA) is a reproducible, noninvasive method for assessing AIx (a measure of the contribution that wave reflection makes to the arterial pressure waveform). The amplitude and timing of the reflected wave ultimately depends on the stiffness of the small (pre-resistance) vessels and large arteries, and thus, AIx provides a measure of systemic arterial stiffness. A high-fidelity micro manometer was used to obtain accurate readings of the peripheral pressure waveforms by flattening, but not occluding, the radial artery of the dominant arm using gentle pressure. AIx was defined as the augmentation (difference between systolic peaks) expressed as a percentage of the overall pulse pressure. Data for change in AIx from Day 1 to 42 was presented.
Time frame: Day 1 to Day 42
Change in Pulse Wave Velocity (PWV) From Day 1 to Day 42
PWV was assessed with a high-fidelity micro manometer which was used to obtain accurate readings of the peripheral pressure waveforms by flattening, but not occluding, the carotid and femoral arteries as the two points of measure. Data for change in PWV from Day 1 to 42 was presented.
Time frame: Day 1 to Day 42
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/birth effect.
Time frame: Up to 59 days
Number of Participants With Any AE of Special Interest (AESI)
AESIs were identified based on non-clinical studies with daprodustat, clinical experience with recombinant human erythropoietins (rhEPOs), and current information regarding hypoxia-inducible factor (HIF)-regulated pathways in mediating hypoxia-associated pathophysiology. The AESIs for daprodustat were identified as follows: Thrombosis and/or tissue ischemia secondary to excessive erythropoiesis; Death, MI, stroke, heart failure, thromboembolic events, thrombosis of vascular access; Cardiomyopathy; Pulmonary artery hypertension; Cancer-related mortality and tumor progression and recurrence Esophageal and gastric erosions; Proliferative retinopathy, macular edema, choroidal neovascularization; Exacerbation of rheumatoid arthritis and Worsening of hypertension.
Time frame: Up to 59 days
Number of Participants Discontinuing the Randomized Study Treatment
Number of participants who discontinued the randomized study treatment were assessed.
Time frame: Up to Day 42
Absolute Values of Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP and SBP were measured in a semi-supine position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Time frame: Days 1, 14, 28, 42 and 59
Change From Baseline in DBP and SBP
DBP and SBP were measured in a semi-supine position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 14, 28, 42 and 59
Absolute Values of Electrocardiogram (ECG) Mean Heart Rate
Full 12-lead ECG were recorded with the participant in a semi-supine position to measure heart rate.
Time frame: Days 1, 42 and 59
Change From Baseline in ECG Mean Heart Rate
Full 12-lead ECG were recorded with the participant in a semi-supine position to measure heart rate. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 42 and 59
Absolute Values of ECG Parameters- PR Interval, QRS Interval, and QT Interval and QT Interval Corrected for Heart Rate Using Bazett's Formula (QTcB)
Full 12-lead ECGs were recorded with the participant in a semi-supine position to measure PR interval, QRS duration, QT interval and QTcB, calculated (machine read or manually).
Time frame: Days 1, 42 and 59
Change From Baseline in ECG Parameters- PR Interval, QRS Duration, and QT Interval and QTcB
Full 12-lead ECGs were recorded with the participant in a semi-supine position to measure PR interval, QRS duration, QT (uncorrected) interval and QTcB, calculated (machine read or manually). Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 42 and 59
Absolute Values of the Hematology Parameters of Platelet Count, White Blood Cell (WBC) Count (Absolute), Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils
Blood samples were collected for the analysis of hematology parameters including platelet count, leukocytes, basophils, eosinophils, lymphocytes, monocytes and neutrophils.
Time frame: Days 1, 42 and 59
Change From Baseline in Hematology Parameters of Platelet Count, Leukocytes, Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils
Blood samples were collected for the analysis of hematology parameters including platelet count, WBC count (Absolute), basophils, eosinophils, lymphocytes, monocytes and neutrophils. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 42 and 59
Absolute Values of the Hematology Parameter of Red Blood Cell (RBC) Count and Reticulocyte Count (RC)
Blood samples were collected for the analysis of hematology parameters including RBC count and RC.
Time frame: Days 1, 42 and 59
Change From Baseline in Hematology Parameters of RBC Count and RC
Blood samples were collected for the analysis of hematology parameters including RBC count and RC. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 42 and 59
Absolute Values of the Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC)
Blood samples were collected for the analysis of hematology parameters including hemoglobin and MCHC.
Time frame: Days 1, 42 and 59
Change From Baseline in Hematology Parameters- Hemoglobin and MCHC
Blood samples were collected for the analysis of hematology parameters including hemoglobin and MCHC. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 42 and 59
Absolute Values of Hematology Parameter: Hematocrit
Blood samples were collected for the analysis of hematology parameters including hematocrit.
Time frame: Days 1, 42 and 59
Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected for the analysis of hematology parameters including hematocrit. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 42 and 59
Absolute Values of Hematology Parameter of Red Blood Cell Distribution Width (RDW)
Blood samples were collected for the analysis of hematology parameters including RDW.
Time frame: Days 1, 42 and 59
Change From Baseline in RDW
Blood samples were collected for the analysis of hematology parameters including RDW. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 42 and 59
Absolute Values of the Hematology Parameter of Mean Corpuscular Hemoglobin (MCH)
Blood samples were collected for the analysis of hematology parameters including MCH.
Time frame: Days 1, 42 and 59
Change From Baseline in Hematology Parameter of MCH
Blood samples were collected for the analysis of hematology parameters including MCH. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 42 and 59
Absolute Values of the Hematology Parameter of Mean Corpuscular Volume (MCV)
Blood samples were collected for the analysis of hematology parameters including MCV.
Time frame: Days 1, 42 and 59
Change From Baseline in Hematology Parameter of MCV
Blood samples were collected for the analysis of hematology parameters including MCV. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 42 and 59
Absolute Values of Clinical Chemistry Parameters of Sodium, Potassium, Carbon-dioxide (Total), Chloride, Glucose and Urea
Blood samples will be collected for the analysis of clinical chemistry parameters including; sodium, potassium, carbon-dioxide (total), chloride, glucose and urea.
Time frame: Days 1, 42 and 59
Change From Baseline in Clinical Chemistry Parameter: Sodium, Potassium, Carbon-dioxide (Total), Chloride, Glucose and Urea
Blood samples will be collected for the analysis of clinical chemistry parameters including; sodium, potassium, carbon-dioxide (total), chloride, glucose and urea. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 42 and 59
Absolute Values of Clinical Chemistry Parameters of Creatinine
Blood samples will be collected for the analysis of clinical chemistry parameters including; creatinine.
Time frame: Days 1, 42 and 59
Change From Baseline in Clinical Chemistry Parameter: Creatinine
Blood samples will be collected for the analysis of clinical chemistry parameters including; creatinine. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 42 and 59
Absolute Values of Clinical Chemistry Parameters of Bilirubin (Direct/Indirect and Total)
Blood samples will be collected for the analysis of clinical chemistry parameters including; bilirubin (direct/indirect and total).
Time frame: Days 1, 14, 28, 42 and 59
Change From Baseline in Clinical Chemistry Parameter: Bilirubin (Direct/Indirect and Total)
Blood samples will be collected for the analysis of clinical chemistry parameters including; creatinine and bilirubin (direct/indirect and total). Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 14, 28, 42 and 59
Absolute Values of Clinical Chemistry Parameters of Alanine Transaminase (ALT), Alkaline Phosphatase (ALP) and Aspartate Transaminase (AST)
Blood samples will be collected for the analysis of clinical chemistry parameters including; ALT, ALP and AST.
Time frame: Days 1, 14, 28, 42 and 59
Change From Baseline in Clinical Chemistry Parameter: ALT, ALP and AST
Blood samples will be collected for the analysis of clinical chemistry parameters including; ALT, ALP and AST. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 14, 28, 42 and 59
Absolute Values of Clinical Chemistry Parameters of Albumin
Blood samples will be collected for the analysis of clinical chemistry parameters including; Albumin.
Time frame: Days 1, 14, 28, 42 and 59
Change From Baseline in Clinical Chemistry Parameter: Albumin
Blood samples will be collected for the analysis of clinical chemistry parameters including; Albumin. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Days 14, 28, 42 and 59
This was an open label, parallel group study that evaluated the effect of daprodustat and darbepoetin alfa on forearm blood flow (FBF) in participants with anemia of chronic kidney disease that are not dialysis dependent.
| Milestone | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Started | 2 | 3 |
| Completed | 2 | 2 |
| Not completed | 0 | 1 |
| Withdrew: Protocol defined stopping criteria | 0 | 1 |
Venous occlusion plethysmography was used for FBF assessment. Acetylcholine (ACH) was infused intra-arterially at 7.5, 15 and 30 micrograms/minute (ug/min) each for 6 minutes per infusion. FBF ratio was defined as the ratio of a participant's treatment (infused) arm value divided by the non-treatment (non-infused) arm value. The overall ratio was determined by taking the participant's Day 42 FBF ratio and dividing by the Day 1 FBF ratio.
| Ratio | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| ACH 7.5 ug/min, n=2, 2 | 1.1304 ± 0.30030 | 0.4351 ± 0.17032 |
| ACH 15 ug/min, n=1, 2 | 0.7866 ± NA | 0.6183 ± 0.00435 |
| ACH 30 ug/min, n=1, 2 | 1.1328 ± NA | 0.8090 ± 0.28395 |
Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. Measures were made in both arms concurrently. Change in the absolute FBF from Day 1 to Day 42 in response to acetylcholine is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to acetylcholine.
| ug/min | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| 7.5 ug/min, n=2, 2 | 8.3180 ± 4.50592 | -6.0360 ± 3.09976 |
| 15 ug/min, n=1, 2 | -4.6374 ± NA | -8.8299 ± 9.98143 |
| 30 ug/min, n=1, 2 | -2.6735 ± NA | -4.5121 ± 5.66731 |
Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. FBF ratio was defined as the ratio of a participant's treatment (infused) arm value divided by the non-treatment (non-infused) arm value. The overall ratio was determined by taking the participant's Day 42 FBF ratio and dividing by the Day 1 FBF ratio.
| Ratio | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| 3 ug/min | 1.0388 ± NA | 0.7420 ± 0.07407 |
| 10 ug/min | 2.1447 ± NA | 0.7022 ± 0.00860 |
Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF from Day 1 to Day 42 in response to sodium nitroprusside is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to sodium nitroprusside.
| ug/min | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| 3 ug/min | -0.2560 ± NA | 0.3844 ± 0.52197 |
| 10 ug/min | 6.8103 ± NA | -0.2873 ± 1.11519 |
Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 micromoles per minute (umol/min) each infused for 6 minutes into the brachial artery of the test arm. FBF ratio was defined as the ratio of a participant's treatment (infused) arm value divided by the non-treatment (non-infused) arm value. The overall ratio was determined by taking the participant's Day 42 FBF ratio and dividing by the Day 1 FBF ratio.
| Ratio | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| 2 umol/min | 0.7426 ± NA | 0.9024 ± NA |
| 8 umol/min | 0.4975 ± NA | 0.8690 ± NA |
Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF from Day 1 to Day 42 in response to L-NMMA is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to L-NMMA.
| umol/min | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| 2 umol/min | 1.1508 ± NA | 0.3558 ± NA |
| 8 umol/min | 0.0974 ± NA | 0.0399 ± NA |
Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio.
| Ratio | Daprodustat |
|---|---|
| 7.5 ug/min, n=2 | 0.2744 ± 0.91996 |
| 15 ug/min, n=1 | -0.8503 ± NA |
| 30 ug/min, n=1 | 0.5482 ± NA |
Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio.
| Ratio | Daprodustat |
|---|---|
| 3 ug/min | 0.1618 ± NA |
| 10 ug/min | 3.2651 ± NA |
Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio.
| Ratio | Daprodustat |
|---|---|
| 2 umol/min | -0.3896 ± NA |
| 8 umol/min | -0.7216 ± NA |
Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio.
| Ratio | Darbepoetin Alfa |
|---|---|
| 7.5 ug/min | -2.0376 ± 0.63291 |
| 15 ug/min | -1.4559 ± 0.01558 |
| 30 ug/min | -1.0652 ± 1.56389 |
Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio.
| Ratio | Darbepoetin Alfa |
|---|---|
| 3 ug/min | -0.7503 ± 0.26692 |
| 10 ug/min | -1.2405 ± 0.15366 |
Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio.
| Ratio | Darbepoetin Alfa |
|---|---|
| 2 umol/min | -0.081 ± NA |
| 8 umol/min | -0.1351 ± NA |
Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. Measures were made in both arms concurrently. Change in the absolute FBF in response to acetylcholine at Day 42 vs Day1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to acetylcholine in participants treated with daprodustat.
| ug/min | Daprodustat |
|---|---|
| 7.5 ug/min, n=2 | 8.3180 ± 4.50592 |
| 15 ug/min, n=1 | -4.6374 ± NA |
| 30 ug/min, n=1 | -2.6735 ± NA |
Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF in response to sodium nitroprusside at Day 42 vs Day 1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to sodium nitroprusside in participants treated with daprodustat.
| ug/min | Daprodustat |
|---|---|
| 3 ug/min | -0.2560 ± NA |
| 10 ug/min | 6.8103 ± NA |
Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF in response to L-NMMA at Day 42 vs Day 1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to L-NMMA in participants treated with daprodustat.
| umol/min | Daprodustat |
|---|---|
| 2 umol/min | 1.1508 ± NA |
| 8 umol/min | 0.0974 ± NA |
Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. Measures were made in both arms concurrently. Change in the absolute FBF in response to acetylcholine at Day 42 vs Day1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to acetylcholine in participants treated with darbepoetin alfa.
| ug/min | Darbepoetin Alfa |
|---|---|
| 7.5 ug/min | -6.0360 ± 3.09976 |
| 15 ug/min | -8.8299 ± 9.98143 |
| 30 ug/min | -4.5121 ± 5.66731 |
Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF in response to sodium nitroprusside at Day 42 vs Day 1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to sodium nitroprusside in participants treated with darbepoetin alfa.
| ug/min | Darbepoetin Alfa |
|---|---|
| 3 ug/min | 0.3844 ± 0.52197 |
| 10 ug/min | -0.2873 ± 1.11519 |
Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF in response to L-NMMA at Day 42 vs Day 1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to L-NMMA in participants treated with darbepoetin alfa.
| umol/min | Darbepoetin Alfa |
|---|---|
| 2 umol/min | 0.3558 ± NA |
| 8 umol/min | 0.0399 ± NA |
Pulse wave analysis (PWA) is a reproducible, noninvasive method for assessing AIx (a measure of the contribution that wave reflection makes to the arterial pressure waveform). The amplitude and timing of the reflected wave ultimately depends on the stiffness of the small (pre-resistance) vessels and large arteries, and thus, AIx provides a measure of systemic arterial stiffness. A high-fidelity micro manometer was used to obtain accurate readings of the peripheral pressure waveforms by flattening, but not occluding, the radial artery of the dominant arm using gentle pressure. AIx was defined as the augmentation (difference between systolic peaks) expressed as a percentage of the overall pulse pressure. Data for change in AIx from Day 1 to 42 was presented.
| Percentage | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Change in Augmentation Index (AIx) From Day 1 to 42 | -3.000 ± 0.0000 | -4.000 ± 2.8284 |
PWV was assessed with a high-fidelity micro manometer which was used to obtain accurate readings of the peripheral pressure waveforms by flattening, but not occluding, the carotid and femoral arteries as the two points of measure. Data for change in PWV from Day 1 to 42 was presented.
| meters per second (m/sec) | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Change in Pulse Wave Velocity (PWV) From Day 1 to Day 42 | 2.075 ± 1.4496 | 0.100 ± 0.2828 |
An AE is any untoward medical occurrence in a clinical study participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/birth effect.
| Participants | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Any AEs | 0 | 1 |
| Any SAEs | 0 | 0 |
AESIs were identified based on non-clinical studies with daprodustat, clinical experience with recombinant human erythropoietins (rhEPOs), and current information regarding hypoxia-inducible factor (HIF)-regulated pathways in mediating hypoxia-associated pathophysiology. The AESIs for daprodustat were identified as follows: Thrombosis and/or tissue ischemia secondary to excessive erythropoiesis; Death, MI, stroke, heart failure, thromboembolic events, thrombosis of vascular access; Cardiomyopathy; Pulmonary artery hypertension; Cancer-related mortality and tumor progression and recurrence Esophageal and gastric erosions; Proliferative retinopathy, macular edema, choroidal neovascularization; Exacerbation of rheumatoid arthritis and Worsening of hypertension.
| Participants | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Number of Participants With Any AE of Special Interest (AESI) | 0 | 0 |
Number of participants who discontinued the randomized study treatment were assessed.
| Participants | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Number of Participants Discontinuing the Randomized Study Treatment | 0 | 0 |
DBP and SBP were measured in a semi-supine position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
| millimeters of mercury (mmHg) | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| DBP, Day 1, n=2, 3 | 73.5 ± 13.44 | 69.3 ± 13.05 |
| DBP, Day 14, n=2, 3 | 67.0 ± 5.66 | 74.3 ± 13.05 |
| DBP, Day 28, n=2, 3 | 73.5 ± 7.78 | 79.3 ± 25.54 |
| DBP, Day 42, n=2, 2 | 76.0 ± 9.90 | 73.0 ± 8.49 |
| DBP, Day 59, n=2, 3 | 69.5 ± 9.19 | 82.7 ± 18.15 |
| SBP, Day 1, n=2, 3 | 144.0 ± 43.84 | 134.3 ± 18.34 |
| SBP, Day 14, n=2, 3 | 130.0 ± 28.28 | 127.7 ± 23.25 |
| SBP, Day 28, n=2, 3 | 135.5 ± 12.02 | 147.3 ± 39.63 |
| SBP, Day 42, n=2, 2 | 145.5 ± 33.23 | 148.0 ± 45.25 |
| SBP, Day 59, n=2, 3 | 135.5 ± 31.82 | 142.3 ± 29.14 |
DBP and SBP were measured in a semi-supine position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| mmHg | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| DBP, Day 14, n=2, 3 | -6.5 ± 7.78 | 5.0 ± 0.00 |
| DBP, Day 28, n=2, 3 | 0.0 ± 21.21 | 10.0 ± 13.00 |
| DBP, Day 42, n=2, 2 | 2.5 ± 3.54 | 10.5 ± 0.71 |
| DBP, Day 59, n=2, 3 | -4.0 ± 4.24 | 13.3 ± 5.13 |
| SBP, Day 14, n=2, 3 | -14.0 ± 15.56 | -6.7 ± 4.93 |
| SBP, Day 28, n=2, 3 | -8.5 ± 31.82 | 13.0 ± 38.43 |
| SBP, Day 42, n=2, 2 | 1.5 ± 10.61 | 10.5 ± 20.51 |
| SBP, Day 59, n=2, 3 | -8.5 ± 12.02 | 8.0 ± 24.02 |
Full 12-lead ECG were recorded with the participant in a semi-supine position to measure heart rate.
| Beats per minute | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Day 1, n=2, 3 | 69.0 ± 2.83 | 70.0 ± 14.11 |
| Day 42, n=2, 2 | 61.0 ± 14.14 | 62.0 ± 9.90 |
| Day 59, n=2, 3 | 71.5 ± 9.19 | 73.7 ± 20.03 |
Full 12-lead ECG were recorded with the participant in a semi-supine position to measure heart rate. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Beats per minute | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Day 42, n=2, 2 | -8.0 ± 11.31 | -0.5 ± 2.12 |
| Day 59, n=2, 3 | 2.5 ± 12.02 | 3.7 ± 9.50 |
Full 12-lead ECGs were recorded with the participant in a semi-supine position to measure PR interval, QRS duration, QT interval and QTcB, calculated (machine read or manually).
| Milliseconds | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| PR Interval, Day 1, n=2, 3 | 139.0 ± 1.41 | 181.7 ± 23.16 |
| PR Interval, Day 42, n=2, 2 | 146.5 ± 7.78 | 192.5 ± 10.61 |
| PR Interval, Day 59, n=2, 3 | 146.5 ± 2.12 | 182.0 ± 18.00 |
| QRS Duration, Day 1, n=2, 3 | 87.0 ± 7.07 | 94.7 ± 5.03 |
| QRS Duration, Day 42, n=2, 2 | 88.5 ± 9.19 | 96.5 ± 10.61 |
| QRS Duration, Day 59, n=2, 3 | 87.0 ± 9.90 | 95.3 ± 7.02 |
| QT Interval, Day 1, n=2, 3 | 395.5 ± 6.36 | 391.3 ± 14.47 |
| QT Interval, Day 42, n=2, 2 | 413.5 ± 20.51 | 388.0 ± 11.31 |
| QT Interval, Day 59, n=2, 3 | 383.5 ± 44.55 | 382.3 ± 33.71 |
| QTcB Interval, Day 1, n=2, 3 | 424.0 ± 1.41 | 420.7 ± 31.79 |
| QTcB Interval, Day 42, n=2, 2 | 414.5 ± 27.58 | 393.0 ± 19.80 |
| QTcB Interval, Day 59, n=2, 3 | 416.5 ± 21.92 | 417.3 ± 33.32 |
Full 12-lead ECGs were recorded with the participant in a semi-supine position to measure PR interval, QRS duration, QT (uncorrected) interval and QTcB, calculated (machine read or manually). Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Milliseconds | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| PR Interval, Day 42, n=2, 2 | 7.5 ± 6.36 | -2.0 ± 19.80 |
| PR Interval, Day 59, n=2, 3 | 7.5 ± 0.71 | 0.3 ± 16.86 |
| QRS Duration, Day 42, n=2, 2 | 1.5 ± 2.12 | 1.5 ± 3.54 |
| QRS Duration, Day 59, n=2, 3 | 0.0 ± 2.83 | 0.7 ± 2.31 |
| QT Interval, Day 42, n=2, 2 | 18.0 ± 14.14 | -7.0 ± 7.07 |
| QT Interval, Day 59, n=2, 3 | -12.0 ± 50.91 | -9.0 ± 19.67 |
| QTcB Interval, Day 42, n=2, 2 | -9.5 ± 26.16 | -9.5 ± 13.44 |
| QTcB Interval, Day 59, n=2, 3 | -7.5 ± 20.51 | -3.3 ± 8.02 |
Blood samples were collected for the analysis of hematology parameters including platelet count, leukocytes, basophils, eosinophils, lymphocytes, monocytes and neutrophils.
| Giga cells per Liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Platelet count, Day 1, n=2, 3 | 199.0 ± 63.64 | 191.7 ± 68.13 |
| Platelet count, Day 42, n=2, 2 | 203.5 ± 57.28 | 121.5 ± 13.44 |
| Platelet count, Day 59, n=2, 3 | 193.0 ± 41.01 | 50.08 ± 50.08 |
| Leukocytes, Day 1, n=2, 3 | 5.05 ± 1.202 | 6.30 ± 2.117 |
| Leukocytes, Day 42, n=2, 2 | 6.05 ± 2.616 | 5.75 ± 2.051 |
| Leukocytes, Day 59, n=2, 3 | 5.30 ± 1.414 | 7.20 ± 2.261 |
| Basophils, Day 1, n=2, 3 | 0.045 ± 0.0212 | 0.057 ± 0.0503 |
| Basophils, Day 42, n=2, 2 | 0.045 ± 0.0212 | 0.045 ± 0.0212 |
| Basophils, Day 59, n=2, 3 | 0.035 ± 0.0071 | 0.050 ± 0.0400 |
| Eosinophils, Day 1, n=2, 3 | 0.295 ± 0.1485 | 0.230 ± 0.1353 |
| Eosinophils, Day 42, n=2, 2 | 0.300 ± 0.1980 | 0.175 ± 0.0778 |
| Eosinophils, Day 59, n=2, 3 | 0.245 ± 0.1485 | 0.220 ± 0.1311 |
| Lymphocytes, Day 1, n=2, 3 | 1.160 ± 0.2404 | 2.037 ± 1.4989 |
| Lymphocytes, Day 42, n=2, 2 | 1.275 ± 0.2616 | 1.150 ± 0.4808 |
| Lymphocytes, Day 59, n=2, 3 | 0.785 ± 0.3748 | 2.033 ± 1.3580 |
| Monocytes, Day 1, n=2, 3 | 0.400 ± 0.0566 | 0.607 ± 0.3147 |
| Monocytes, Day 42, n=2, 2 | 0.415 ± 0.0071 | 0.445 ± 0.2192 |
| Monocytes, Day 59, n=2, 3 | 0.415 ± 0.0778 | 0.563 ± 0.2574 |
| Neutrophils, Day 1, n=2, 3 | 3.160 ± 1.3576 | 3.387 ± 0.2053 |
| Neutrophils, Day 42, n=2, 2 | 4.010 ± 2.6870 | 3.970 ± 2.1920 |
| Neutrophils, Day 59, n=2, 3 | 3.825 ± 1.0112 | 4.343 ± 1.0060 |
Blood samples were collected for the analysis of hematology parameters including platelet count, WBC count (Absolute), basophils, eosinophils, lymphocytes, monocytes and neutrophils. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Giga cells per Liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Platelet count, Day 42, n=2, 2 | 4.5 ± 6.36 | -51.0 ± 70.71 |
| Platelet count, Day 59, n=2, 3 | -6.0 ± 22.63 | -26.3 ± 51.98 |
| Leukocytes, Day 42, n=2, 2 | 1.00 ± 1.414 | 0.65 ± 2.616 |
| Leukocytes, Day 59, n=2, 3 | 0.25 ± 0.212 | 0.90 ± 1.054 |
| Basophils, Day 42, n=2, 2 | 0.000 ± 0.0000 | 0.015 ± 0.0071 |
| Basophils, Day 59, n=2, 3 | -0.010 ± 0.0283 | -0.007 ± 0.0115 |
| Eosinophils, Day 42, n=2, 2 | 0.005 ± 0.0495 | 0.015 ± 0.0071 |
| Eosinophils, Day 59, n=2, 3 | -0.050 ± 0.0000 | -0.010 ± 0.0100 |
| Lymphocytes, Day 42, n=2, 2 | 0.115 ± 0.0212 | -0.040 ± 0.0424 |
| Lymphocytes, Day 59, n=2, 3 | -0.375 ± 0.6152 | -0.003 ± 0.1443 |
| Monocytes, Day 42, n=2, 2 | 0.015 ± 0.0636 | 0.020 ± 0.2263 |
| Monocytes, Day 59, n=2, 3 | 0.015 ± 0.0212 | -0.043 ± 0.0586 |
| Neutrophils, Day 42, n=2, 2 | 0.850 ± 1.3294 | 0.670 ± 2.3900 |
| Neutrophils, Day 59, n=2, 3 | 0.665 ± 0.3465 | 0.957 ± 1.0929 |
Blood samples were collected for the analysis of hematology parameters including RBC count and RC.
| Trillion cells per liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| RBC, Day 1, n=2, 3 | 3.45 ± 0.354 | 3.20 ± 0.300 |
| RBC, Day 42, n=2, 2 | 3.30 ± 0.283 | 3.65 ± 0.071 |
| RBC, Day 59, n=2, 3 | 3.35 ± 0.354 | 3.63 ± 0.493 |
| RC, Day 1, n=2, 3 | 0.04090 ± 0.018102 | 0.06090 ± 0.038112 |
| RC, Day 42, n=2, 2 | 0.04610 ± 0.023052 | 0.07970 ± 0.057983 |
| RC, Day 59, n=2, 3 | 0.03490 ± 0.014708 | 0.04580 ± 0.049537 |
Blood samples were collected for the analysis of hematology parameters including RBC count and RC. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Trillion cells per liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| RBC, Day 42, n=2, 2 | -0.15 ± 0.071 | 0.60 ± 0.141 |
| RBC, Day 59, n=2, 3 | -0.10 ± 0.000 | 0.43 ± 0.252 |
| RC, Day 42, n=2, 2 | 0.00520 ± 0.004950 | 0.00815 ± 0.010819 |
| RC, Day 59, n=2, 3 | -0.00600 ± 0.003394 | -0.01510 ± 0.011467 |
Blood samples were collected for the analysis of hematology parameters including hemoglobin and MCHC.
| Grams per deciliter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Hemoglobin, Day 1, n=2, 3 | 10.60 ± 0.849 | 9.77 ± 0.586 |
| Hemoglobin, Day 42, n=2, 2 | 10.45 ± 0.778 | 11.40 ± 0.424 |
| Hemoglobin, Day 59, n=2, 3 | 10.40 ± 0.849 | 11.27 ± 1.002 |
| MCHC, Day 1, n=2, 3 | 34.10 ± 0.000 | 34.23 ± 0.351 |
| MCHC, Day 42, n=2, 2 | 34.10 ± 0.141 | 33.75 ± 1.909 |
| MCHC, Day 59, n=2, 3 | 34.00 ± 0.141 | 34.33 ± 1.447 |
Blood samples were collected for the analysis of hematology parameters including hemoglobin and MCHC. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Grams per deciliter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Hemoglobin, Day 42, n=2, 2 | -0.15 ± 0.071 | 1.85 ± 0.212 |
| Hemoglobin, Day 59, n=2, 3 | -0.20 ± 0.000 | 1.50 ± 0.520 |
| MCHC, Day 42, n=2, 2 | 0.00 ± 0.141 | -0.65 ± 1.626 |
| MCHC, Day 59, n=2, 3 | -0.10 ± 0.141 | 0.10 ± 1.127 |
Blood samples were collected for the analysis of hematology parameters including hematocrit.
| Proportion of red blood cells in blood | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Day 1, n=2, 3 | 0.3105 ± 0.02616 | 0.2850 ± 0.01769 |
| Day 42, n=2, 2 | 0.3065 ± 0.02475 | 0.3385 ± 0.00636 |
| Day 59, n=2, 3 | 0.3065 ± 0.02475 | 0.3277 ± 0.03412 |
Blood samples were collected for the analysis of hematology parameters including hematocrit. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Proportion of red blood cells in blood | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Day 42, n=2, 2 | -0.0040 ± 0.00141 | 0.0615 ± 0.02192 |
| Day 59, n=2, 3 | -0.0040 ± 0.00141 | 0.0427 ± 0.02212 |
Blood samples were collected for the analysis of hematology parameters including RDW.
| Percentage of width | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Day 1, n=2, 3 | 0.3105 ± 0.02616 | 0.2850 ± 0.01769 |
| Day 42, n=2, 2 | 13.45 ± 0.212 | 14.00 ± 0.424 |
| Day 59, n=2, 3 | 13.20 ± 0.141 | 13.70 ± 0.200 |
Blood samples were collected for the analysis of hematology parameters including RDW. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Percentage of width | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Day 42, n=2, 2 | 0.00 ± 0.424 | 1.15 ± 0.636 |
| Day 59, n=2, 3 | -0.25 ± 0.354 | 0.70 ± 0.436 |
Blood samples were collected for the analysis of hematology parameters including MCH.
| Picograms | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Day 1, n=2, 3 | 30.95 ± 0.354 | 30.67 ± 1.457 |
| Day 42, n=2, 2 | 31.40 ± 0.424 | 31.40 ± 0.707 |
| Day 59, n=2, 3 | 31.10 ± 0.141 | 30.93 ± 1.716 |
Blood samples were collected for the analysis of hematology parameters including MCH. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Picograms | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Day 42, n=2, 2 | 0.45 ± 0.071 | -0.10 ± 0.990 |
| Day 59, n=2, 3 | 0.15 ± 0.212 | 0.27 ± 0.862 |
Blood samples were collected for the analysis of hematology parameters including MCV.
| Femtoliters | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Day 1, n=2, 3 | 91.0 ± 1.41 | 89.7 ± 3.51 |
| Day 42, n=2, 2 | 92.0 ± 1.41 | 93.0 ± 2.83 |
| Day 59, n=2, 3 | 91.5 ± 0.71 | 90.0 ± 3.00 |
Blood samples were collected for the analysis of hematology parameters including MCV. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Femtoliters | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Day 42, n=2, 2 | 1.0 ± 0.00 | 1.5 ± 0.71 |
| Day 59, n=2, 3 | 0.5 ± 0.71 | 0.3 ± 0.58 |
Blood samples will be collected for the analysis of clinical chemistry parameters including; sodium, potassium, carbon-dioxide (total), chloride, glucose and urea.
| Millimoles per Liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Sodium, Day 1, n=2, 3 | 140.0 ± 1.41 | 136.7 ± 0.58 |
| Sodium, Day 42, n=2, 2 | 139.5 ± 3.54 | 135.0 ± 7.07 |
| Sodium, Day 59, n=2, 3 | 138.5 ± 0.71 | 136.0 ± 2.65 |
| Potassium, Day 1, n=2, 3 | 4.70 ± 0.141 | 5.03 ± 0.757 |
| Potassium, Day 42, n=2, 2 | 4.55 ± 0.495 | 5.15 ± 0.495 |
| Potassium, Day 59, n=2, 3 | 4.45 ± 0.071 | 4.77 ± 0.306 |
| Carbon-dioxide (total), Day 1, n=2, 3 | 20.5 ± 3.54 | 19.0 ± 3.46 |
| Carbon-dioxide (total), Day 42, n=2, 2 | 22.0 ± 1.41 | 19.0 ± 0.00 |
| Carbon-dioxide (total), Day 59, n=2, 3 | 22.5 ± 2.12 | 21.0 ± 2.00 |
| Chloride, Day 1, n=2, 3 | 108.0 ± 0.00 | 105.7 ± 5.03 |
| Chloride, Day 42, n=2, 2 | 108.0 ± 4.24 | 104.0 ± 9.90 |
| Chloride, Day 59, n=2, 3 | 108.0 ± 2.83 | 104.7 ± 3.51 |
| Glucose, Day 1, n=2, 3 | 7.60 ± 3.111 | 6.40 ± 4.424 |
| Glucose, Day 42, n=2, 2 | 6.95 ± 2.333 | 12.50 ± 12.162 |
| Glucose, Day 59, n=2, 3 | 7.45 ± 4.172 | 10.10 ± 7.066 |
| Urea, Day 1, n=2, 3 | 18.00 ± 2.828 | 16.67 ± 5.508 |
| Urea, Day 42, n=2, 2 | 16.75 ± 2.475 | 21.00 ± 0.707 |
| Urea, Day 59, n=2, 3 | 16.50 ± 0.707 | 19.33 ± 5.795 |
Blood samples will be collected for the analysis of clinical chemistry parameters including; sodium, potassium, carbon-dioxide (total), chloride, glucose and urea. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Millimoles per Liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Sodium, Day 42, n=2, 2 | -0.5 ± 4.95 | -1.5 ± 6.36 |
| Sodium, Day 59, n=2, 3 | -1.5 ± 2.12 | -0.7 ± 2.31 |
| Potassium, Day 42, n=2, 2 | -0.15 ± 0.354 | -0.05 ± 0.495 |
| Potassium, Day 59, n=2, 3 | -0.25 ± 0.071 | -0.27 ± 0.503 |
| Carbon-dioxide (total), Day 42, n=2, 2 | 1.5 ± 4.95 | 1.0 ± 4.24 |
| Carbon-dioxide (total), Day 59, n=2, 3 | 2.0 ± 1.41 | 2.0 ± 2.00 |
| Chloride, Day 42, n=2, 2 | 0.0 ± 4.24 | -2.0 ± 2.83 |
| Chloride, Day 59, n=2, 3 | 0.0 ± 2.83 | 1.73 ± 1.73 |
| Glucose, Day 42, n=2, 2 | -0.65 ± 0.778 | 4.25 ± 7.849 |
| Glucose, Day 59, n=2, 3 | -0.15 ± 1.061 | 3.70 ± 3.477 |
| Urea, Day 42, n=2, 2 | -1.25 ± 5.303 | 3.00 ± 7.778 |
| Urea, Day 59, n=2, 3 | -1.50 ± 3.536 | 2.67 ± 2.754 |
Blood samples will be collected for the analysis of clinical chemistry parameters including; creatinine.
| Micromoles per Liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Creatinine, Day 1, n=2, 3 | 246.65 ± 9.970 | 225.40 ± 74.164 |
| Creatinine, Day 42, n=2, 2 | 249.75 ± 15.627 | 272.25 ± 88.742 |
| Creatinine, Day 59, n=2, 3 | 260.35 ± 8.132 | 245.17 ± 91.086 |
Blood samples will be collected for the analysis of clinical chemistry parameters including; creatinine. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Micromoles per Liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Creatinine, Day 42, n=2, 2 | 3.10 ± 5.657 | 36.70 ± 13.152 |
| Creatinine, Day 59, n=2, 3 | 13.70 ± 18.102 | 19.77 ± 33.416 |
Blood samples will be collected for the analysis of clinical chemistry parameters including; bilirubin (direct/indirect and total).
| Micromoles per Liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Bilirubin total, Day 1, n=2, 3 | 5.0 ± 1.41 | 6.0 ± 0.00 |
| Bilirubin total, Day 14, n=2, 3 | 5.0 ± 1.41 | 7.3 ± 1.15 |
| Bilirubin total, Day 28, n=2, 3 | 6.0 ± 0.00 | 6.0 ± 0.00 |
| Bilirubin total, Day 42, n=2, 2 | 6.0 ± 0.00 | 9.0 ± 4.24 |
| Bilirubin total, Day 59, n=2, 3 | 5.0 ± 1.41 | 6.7 ± 1.15 |
| Direct Bilirubin, Day 1, n=2, 2 | 1.0 ± 1.41 | 2.0 ± 0.00 |
| Direct Bilirubin, Day 14, n=2, 2 | 1.0 ± 1.41 | 2.0 ± 0.00 |
| Direct Bilirubin, Day 28, n=2, 2 | 1.0 ± 1.41 | 2.0 ± 0.00 |
| Direct Bilirubin, Day 42, n=2, 1 | 2.0 ± 0.00 | 2.0 ± NA |
| Direct Bilirubin, Day 59, n=2, 2 | 2.0 ± 0.00 | 2.0 ± 0.00 |
| Indirect Bilirubin, Day 1, n=2, 2 | 4.0 ± 0.00 | 4.0 ± 0.00 |
| Indirect Bilirubin, Day 14, n=2, 2 | 4.0 ± 0.00 | 5.0 ± 1.41 |
| Indirect Bilirubin, Day 28, n=2, 2 | 5.0 ± 1.41 | 4.0 ± 0.00 |
| Indirect Bilirubin, Day 42, n=2, 1 | 4.0 ± 0.00 | 10.0 ± NA |
| Indirect Bilirubin, Day 59, n=2, 2 | 3.0 ± 1.41 | 5.0 ± 1.41 |
Blood samples will be collected for the analysis of clinical chemistry parameters including; creatinine and bilirubin (direct/indirect and total). Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Micromoles per Liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Bilirubin total, Day 14, n=2, 3 | 0.0 ± 0.00 | 1.3 ± 1.15 |
| Bilirubin total, Day 28, n=2, 3 | 1.0 ± 1.41 | 0.0 ± 0.00 |
| Bilirubin total, Day 42, n=2, 2 | 1.0 ± 1.41 | 3.0 ± 4.24 |
| Bilirubin total, Day 59, n=2, 3 | 0.0 ± 0.00 | 0.7 ± 1.15 |
| Direct Bilirubin, Day 14, n=2, 2 | 0.0 ± 0.00 | 0.0 ± 0.00 |
| Direct Bilirubin, Day 28, n=2, 2 | 0.0 ± 0.00 | 0.0 ± 0.00 |
| Direct Bilirubin, Day 42, n=2, 1 | 1.0 ± 1.41 | 0.0 ± NA |
| Direct Bilirubin, Day 59, n=2, 2 | 1.0 ± 1.41 | 0.0 ± 0.00 |
| Indirect Bilirubin, Day 14, n=2, 2 | 0.0 ± 0.00 | 1.0 ± 1.41 |
| Indirect Bilirubin, Day 28, n=2, 2 | 1.0 ± 1.41 | 0.0 ± 0.00 |
| Indirect Bilirubin, Day 42, n=2, 1 | 0.0 ± 0.00 | 6.0 ± NA |
| Indirect Bilirubin, Day 59, n=2, 2 | -1.0 ± 1.41 | 1.0 ± 1.41 |
Blood samples will be collected for the analysis of clinical chemistry parameters including; ALT, ALP and AST.
| International units per Liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| ALT, Day 1, n=2, 3 | 21.0 ± 4.24 | 26.7 ± 7.02 |
| ALT, Day 14, n=2, 3 | 15.0 ± 4.24 | 20.3 ± 6.81 |
| ALT, Day 28, n=2, 3 | 15.5 ± 4.95 | 18.3 ± 8.08 |
| ALT, Day 42, n=2, 2 | 16.0 ± 4.24 | 22.0 ± 9.90 |
| ALT, Day 59, n=2, 3 | 20.5 ± 10.61 | 23.3 ± 8.08 |
| ALP, Day 1, n=2, 3 | 113.5 ± 61.52 | 95.0 ± 42.44 |
| ALP, Day 14, n=2, 3 | 97.0 ± 42.43 | 91.0 ± 33.87 |
| ALP, Day 28, n=2, 3 | 99.5 ± 45.96 | 91.7 ± 38.40 |
| ALP, Day 42, n=2, 2 | 99.0 ± 39.60 | 100.5 ± 37.48 |
| ALP, Day 59, n=2, 3 | 108.5 ± 55.86 | 90.3 ± 29.26 |
| AST, Day 1, n=2, 3 | 19.5 ± 7.78 | 21.7 ± 1.53 |
| AST, Day 14, n=2, 3 | 16.5 ± 7.78 | 18.3 ± 3.51 |
| AST, Day 28, n=2, 3 | 18.0 ± 9.90 | 18.7 ± 7.09 |
| AST, Day 42, n=2, 2 | 17.5 ± 10.61 | 16.5 ± 4.95 |
| AST, Day 59, n=2, 3 | 20.5 ± 10.61 | 19.3 ± 6.03 |
Blood samples will be collected for the analysis of clinical chemistry parameters including; ALT, ALP and AST. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| International units per Liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| ALT, Day 14, n=2, 3 | -6.0 ± 0.00 | -6.3 ± 1.53 |
| ALT, Day 28, n=2, 3 | -5.5 ± 0.71 | -8.3 ± 1.15 |
| ALT, Day 42, n=2, 2 | -5.0 ± 0.00 | -5.0 ± 0.00 |
| ALT, Day 59, n=2, 3 | -0.5 ± 6.36 | -3.3 ± 4.62 |
| ALP, Day 14, n=2, 3 | -16.5 ± 19.09 | -4.0 ± 12.12 |
| ALP, Day 28, n=2, 3 | -14.0 ± 15.56 | -3.3 ± 4.04 |
| ALP, Day 42, n=2, 2 | -14.5 ± 21.92 | -6.5 ± 14.85 |
| ALP, Day 59, n=2, 3 | -5.0 ± 5.66 | -4.7 ± 13.61 |
| AST, Day 14, n=2, 3 | -3.0 ± 0.00 | -3.3 ± 2.08 |
| AST, Day 28, n=2, 3 | -1.5 ± 2.12 | -3.0 ± 6.00 |
| AST, Day 42, n=2, 2 | -2.0 ± 2.83 | -5.0 ± 2.83 |
| AST, Day 59, n=2, 3 | 1.0 ± 2.83 | -2.3 ± 5.03 |
Blood samples will be collected for the analysis of clinical chemistry parameters including; Albumin.
| Grams per Liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Day 1, n=2, 3 | 37.0 ± 5.66 | 41.7 ± 2.31 |
| Day 14, n=2, 3 | 36.5 ± 2.12 | 40.7 ± 3.06 |
| Day 28, n=2, 3 | 35.5 ± 3.54 | 39.3 ± 3.21 |
| Day 42, n=2, 2 | 35.5 ± 3.54 | 38.5 ± 0.71 |
| Day 59, n=2, 3 | 36.5 ± 6.36 | 40.3 ± 1.53 |
Blood samples will be collected for the analysis of clinical chemistry parameters including; Albumin. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
| Grams per Liter | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Day 14, n=2, 3 | -0.05 ± 0.354 | -0.10 ± 0.200 |
| Day 28, n=2, 3 | -0.15 ± 0.212 | -0.23 ± 0.321 |
| Day 42, n=2, 2 | -0.15 ± 0.212 | -0.25 ± 0.354 |
| Day 59, n=2, 3 | -0.05 ± 0.071 | -0.13 ± 0.153 |
Collected over Non-SAEs and SAEs were collected from the start of the treatment and Up to 59 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Daprodustat | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) |
| Darbepoetin Alfa | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) |
| Event | Daprodustat | Darbepoetin Alfa |
|---|---|---|
| Faeces softGastrointestinal disorders | 0/2 | 1/3 |
| Abdominal pain upperGastrointestinal disorders | 0/2 | 1/3 |
| GoutMetabolism and nutrition disorders | 0/2 | 1/3 |
| Bilateral foot discomfort secondary to GoutMetabolism and nutrition disorders | 0/2 | 1/3 |
| Swollen right foot secondary to GoutMetabolism and nutrition disorders | 0/2 | 1/3 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 0/2 | 1/3 |
| Joint swellingMusculoskeletal and connective tissue disorders | 0/2 | 1/3 |
| Age, Continuous(Years) | Daprodustat | Darbepoetin Alfa | Total |
|---|---|---|---|
| Mean | 62.0 ± 2.83 | 53.0 ± 15.72 | 56.6 ± 12.24 |
| Sex: Female, Male(Participants) | Daprodustat | Darbepoetin Alfa | Total |
|---|---|---|---|
| Female | 1 | 1 | 2 |
| Male | 1 | 2 | 3 |
| Race/Ethnicity, Customized(Participants) | Daprodustat | Darbepoetin Alfa | Total |
|---|---|---|---|
| White/Caucasian/European Heritage | 2 | 3 | 5 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Data sharing details ↗ · clinicalstudydatarequest.com
Ran from Jan 2019 to primary completion in May 2019, 4 months.
Results were first posted in Jul 2021, 2 years 1 month after primary completion. A results delay was requested in Dec 2020.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in Mar 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: GSK1278863