AnaemiaPhase 2NCT03029247
Anemia Study in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat-Blood Pressure (ASCEND-BP)
A Phase 2 study testing Daprodustat and Epoetin alfa in people with Anaemia, run by GlaxoSmithKline at 11 sites in United States.
Trial summary
This will be an open-label, randomized, parallel-group study in hemodialysis-dependent (HD) participants with anemia associated with chronic kidney disease (CKD), designed to compare the effects of daprodustat to epoetin alfa on blood pressure (BP). Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Anaemia
- What is being tested?
- Daprodustat and Epoetin alfa
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 11 sitesUnited States
- Study dates
- 27 Jul 2017to 9 Jul 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- More than or equal to 40 years of age, at the time of signing the informed consent
- Stable Hgb 8.5 to 11.5 grams per deciliter (g/dL) inclusive.
- Dialysis frequency: On hemodialysis (HD, hemofiltration or hemodiafiltration) three-to five-times weekly for at least 4 weeks prior to screening.
- A single pool Kt/Vurea >=1.2 based on a historical value obtained within 3 months prior to screening in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio should be at least 65 percent (%).
- Treated with an ESA (epoetins or their biosimilars, darbepoetin, or methoxy polyethylene glycol [PEG]-epoetin beta) for at least 4 weeks prior to screening.
- Participants may be on stable (<=50% change in overall dose and compliance of 80% of prescribed doses in the 4 weeks prior to and including the screening period) maintenance oral or intravenous (IV; <=100 mg/week) iron supplementation. If participants are on oral or IV iron, then doses must be stable for the 4 weeks prior to Washout.
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- Weight: Mid-week weight change between dialysis treatments <5% as assessed post-dialysis at the Screening and Washout visits.
- On at least 1 antihypertensive medication (excluding diuretics) and on that same medication and the same dose for at least 1 week prior to Washout.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and the protocol.
- Willing and able to wear ABPM device for at least 25 hours on two separate sessions.
Who cannot join
- Planned change from HD to peritoneal dialysis within the study time period, or on home dialysis.
- Planned for kidney transplant within the 16 weeks following the Screening visit.
- An epoetin alfa dose of >=360 U/kg/week IV or >=250 U/kg/week subcutaneous (SC), or darbepoetin dose of >=1.8 micrograms (μg)/kg/week IV or SC, or methoxy PEG-epoetin beta dose of >=2.2 μg/kg/week within the 8 weeks prior to screening through Week -4.
- Planned or recorded administration of Mircera (methoxy PEG-epoetin beta) within the 4 weeks prior to the Washout.
- Occurrence of myocardial infarction or acute coronary syndrome within 3 months prior to Washout.
- Stroke or transient ischemic attack within 3 months prior to Washout.
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- Chronic Class 4 heart failure, as defined by the New York Heart Association functional classification system diagnosed prior to Washout.
- QT interval corrected for heart rate using Bazett's formula (QTcB) >500 milliseconds (msec), or QTcB >530 msec in participants with Bundle Branch Block. There is no QTc exclusion for participants with a predominantly paced rhythm.
- Resting post dialysis SBP >160 millimeters of mercury (mmHg); or DBP >100 mmHg at screening or uncontrolled hypertension as determined by the investigator.
- Presence of atrial fibrillation.
- Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosus, rheumatoid arthritis, celiac disease) diagnosed prior to Washout.
- History of bone marrow aplasia or pure red cell aplasia.
- Other causes of anemia including Pernicious anemia, thalassemia major, sickle cell disease or myelodysplastic syndrome.
- Alanine transaminase (ALT) >2 times upper limit of normal (ULN) (screening only) or Bilirubin >1.5 times ULN (screening only) or Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
- Major surgery (excluding vascular access surgery) within the 3 months prior to Washout or planned during the study.
- Blood transfusion within the 8 weeks prior to Washout or an anticipated need for blood transfusion during the study.
- Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal bleeding within the 8 weeks prior to Washout.
- Clinical evidence of acute infection or history of infection requiring IV antibiotic therapy within the 8 weeks prior to Washout.
- History of malignancy within the two years prior to screening through Day 1 or currently receiving treatment for cancer, or has a known complex kidney cyst (e.g., Bosniak Category IIF, III or IV) >=3 centimeters.
- Participants with an upper arm diameter which cannot be measured by oscillometer/ sphygmomanometer cuff or for whom BP cannot be measured in the opposite arm of current vascular access.
- History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
- Use of any prescription or non-prescription drugs or dietary supplements that are prohibited from screening until Washout.
- The participant has participated in a clinical trial and has received an experimental investigational product within the 30 days prior to Day 1 or within 5 half lives of the investigational product prior to screening, whichever is longer.
- 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.
- A female participant is pregnant (as confirmed by a positive serum human chorionic gonadotrophin test for females of reproductive potential only), participant is breastfeeding, or participant is of reproductive potential and does not agree to follow one of the pre-specified contraceptive options
- Vitamin B12 at or below the lower limit of the reference range (may rescreen in a minimum of 8 weeks, following treatment).
- Folate at <2.0 nanograms/milliliter (ng/mL) (4.5 Nanomoles per Liter) (may rescreen in a minimum of 4 weeks, following treatment).
- Ferritin at <100 ng/mL
- Transferrin saturation at <20%.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
GSK Investigational Site
Chicago, Illinois, 60643
GSK Investigational Site
Coral Gables, Florida, 33134
GSK Investigational Site
DeLand, Florida, 32720
GSK Investigational Site
Hollywood, Florida, 33024
GSK Investigational Site
La Mesa, California, 91942
GSK Investigational Site
Lakewood, Colorado, 80228
GSK Investigational Site
Miami, Florida, 33133
GSK Investigational Site
Minneapolis, Minnesota, 55404
GSK Investigational Site
Orlando, Florida, 32809
GSK Investigational Site
San Antonio, Texas, 78215
GSK Investigational Site
Spartanburg, South Carolina, 29301
About this study
Official title: A Randomized, Open-label Study to Evaluate the Effect of Daprodustat on Blood Pressure in Subjects With Anemia Associated With Chronic Kidney Disease on Hemodialysis Switched From a Stable Dose of an Erythropoiesis-stimulating Agent
This will be an open-label, randomized, parallel-group study in hemodialysis-dependent (HD) participants with anemia associated with chronic kidney disease (CKD), designed to compare the effects of daprodustat to epoetin alfa on blood pressure (BP). Participants will be screened for eligibility within 7 and 30 days prior to erythropoesis-stimulating agent (ESA) washout. Following a 2-week ESA washout period, on Day 1 participants will be randomized 1:1 and stratified by prior ESA dose before they undergo Acute Challenge 1, a single dose challenge to compare the acute effects on BP of the highest planned once-daily maintenance dose of daprodustat (24 milligrams [mg]) to the highest starting dose of epoetin alfa (100 units/kilogram [U/kg]). This will be followed by an 8-week hemoglobin (Hgb)-maintenance period, where doses of either daprodustat or epoetin alfa will be administered and adjusted. At the end of Hgb maintenance period, on Day 57 an Acute Challenge 2 will be repeated utilizing the same treatment dose administered in Acute Challenge 1; there will be a follow-up visit within 14+/-3 days after completing treatment.
- Conditions
- Anaemia
- Being tested
- Daprodustat, Epoetin alfa
- Keywords
- Anemia, Daprodustat, Blood pressure, ESA, CKD
- Medical subject headings
- Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaprodustatDrug
Daprodustat will be available as oral tablets at unit dose strength of 1, 2, 4, 6, 8 and 10 mg.
Epoetin alfaDrug
Epoetin alfa will be administered according to local labelling and clinical practice guidelines to keep Hgb in the target range (10.0-11.0 g/dL)
| Study group | Role | What they receive |
|---|---|---|
| Participants receiving Epoetin alfa | Active comparator | On Day 1, participants will undergo 24-hour Acute Challenge 1, in which participants will receive a single dose of 100 U/kg epoetin alfa IV. After completing Acute Challenge 1, participants will enter in an 8-week Hgb maintenance period. At the end of Hgb maintenance period, on Day 57, Acute Challenge 2 will be performed utilizing the same treatment dose administered in Acute Challenge 1. Receives: Drug: Epoetin alfa |
| Participants receiving Daprodustat | Experimental | On Day 1, participants will undergo 24-hour Acute Challenge 1, in which participants will receive 24 mg daprodustat. After completing Acute Challenge 1, participants will enter an 8-week Hgb maintenance period. At the end of Hgb maintenance period, on Day 57, Acute Challenge 2 will be performed utilizing the same treatment dose administered in Acute Challenge 1. Receives: Drug: Daprodustat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average of Systolic Blood Pressure (SBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM) Over 6-hour Post Dosing on Day 57
The effect of daprodustat and epoetin alfa on blood pressure was compared using ABPM after 8 weeks of Hgb maintenace therapy on Day 57. Analysis was based on "analysis of covariance (ANCOVA) with terms for treatment, prior erythropoiesis-stimulating agent (ESA) dose (low/high), post-Hemodialysis dependent (HD)/pre-AC 1 SBP, difference between post-HD/pre-AC 2 SBP and post-HD/pre-AC 1 SBP and treatment by difference in post-HD SBP between AC 1 and 2 interaction." Least square (LS) mean of 6 hour average SBP post AC2 on Day 57 and its corresponding standard error has been presented.
Measured: Up to 6 hours post dose on Day 57
Secondary outcomes (21)
Average of SBP, Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) Measured by ABPM Over 6-hour Post Dosing on Day 1
The initial effect of daprodustat and epoetin alfa on blood pressure was compared using ABPM over 6 hour post-dosing on Day 1. Analysis was based on ANCOVA with terms for treatment, prior ESA dose (low/high), post-HD/pre-AC1 SBP, DBP and MAP. LS mean of 6 hour average SBP, DBP and MAP post AC1 on Day 1 and its corresponding standard error has been presented.
Measured: Up to 6 hours post dose on Day 1
Average of Heart Rate (HR) Measured by ABPM Over 6 Hour Post Dosing on Day 1
The initial effect of daprodustat and epoetin alfa on HR was compared using ABPM over 6 hour post-dosing on Day 1. Analysis was based on ANCOVA with terms for treatment, prior ESA dose (low/high), post-HD/pre-AC1 HR. LS mean of 6 hour average HR post AC1 on Day 1 and its corresponding standard error has been presented.
Measured: Up to 6 hours post dose on Day 1
Area Under the Effect Curve (AUEC) of SBP, DBP and MAP Measured by ABPM Over 24-hour Post Dosing on Day 1
The initial effect of daprodustat and epoetin alfa on blood pressure was compared using AUEC of SBP, DBP and MAP measured by ABPM over 24-hour post dosing on Day 1. Analysis was based on ANCOVA with terms for treatment and prior ESA dose (low/high). LS mean of AUEC up to 24 hours post dose on Day 1 and its corresponding standard error has been presented.
Measured: Up to 24 hours post dose on Day 1
AUEC of HR Measured by ABPM Over 24-hour Post Dosing on Day 1
The initial effect of daprodustat and epoetin alfa on HR was compared using AUEC of HR measured by ABPM over 24-hour post dosing. Analysis was based on ANCOVA with terms for treatment and prior ESA dose (low/high). LS mean of AUEC up to 24 hours post dose on Day 1 and its corresponding standard error has been presented.
Measured: Up to 24 hours post dose on Day 1
Average of DBP and MAP Measured by ABPM Over 6-hour Post Dosing on Day 57
The effect of daprodustat and epoetin alfa on blood pressure was compared using ABPM over 6 hour post-dosing after AC2 on Day 57. Analysis was based on ANCOVA with terms for treatment, prior ESA dose (low/high), post-HD/pre-AC1 DBP and MAP, difference between post-HD/pre-AC2 DBP and MAP and post-HD/pre-AC1 DBP and MAP and treatment by difference in post-HD DBP and MAP between AC1 and 2 interaction. LS mean of 6 hour average DBP and MAP post AC2 on Day 57 and its corresponding standard error has been presented.
Measured: Up to 6 hours post dose on Day 57
Average of HR Measured by ABPM Over 6 Hour Post Dosing on Day 57
The effect of daprodustat and epoetin alfa on HR was compared using ABPM over 6 hour post-dosing. Analysis was based on ANCOVA with terms for treatment, prior ESA dose (low/high), post-HD/pre-AC1 HR, difference between post-HD/pre-AC2 HR and post-HD/pre-AC1 HR and treatment by difference in post-HD HR between AC1 and 2 interaction. LS mean of 6 hour average HR post AC2 on Day 57 and its corresponding standard error has been presented.
Measured: Up to 6 hours post dose on Day 57
AUEC of SBP, DBP and MAP Measured by ABPM Over 24-hour Post Dosing on Day 57
The effect of daprodustat and epoetin alfa on blood pressure was compared using AUEC of SBP, DBP and MAP measured by ABPM over 24-hour post dosing on Day 57. Analysis was based on ANCOVA with terms for treatment and prior ESA dose (low/high). LS mean of AUEC up to 24 hour post dose on Day 57 and its corresponding standard error has been presented.
Measured: Up to 24 hours post dose on Day 57
AUEC of HR Measured by ABPM Over 24-hour Post Dosing on Day 57
The effect of daprodustat and epoetin alfa on HR was compared using AUEC of HR measured by ABPM over 24-hour post dosing on Day 57. Analysis was based on ANCOVA with terms for treatment and prior ESA dose (low/high). LS mean of AUEC up to 24 hour post dose on Day 57 and its corresponding standard error has been presented.
Measured: Up to 24 hours post dose on Day 57
Change From Pre-dose in SBP, DBP and MAP at Day 1
The change from pre-dose in SBP, DBP and MAP was measured using ABPM to compare the initial effect of daprodustat to epoetin alfa after AC1 on Day 1. Change from pre-dose at each timepoint is calculated as measurement at post-dose minus pre-acute challenge 1 measurement.
Measured: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 hours post-dose
Change From Pre-dose in HR at Day 1
The change from pre-dose in HR was measured using ABPM to compare the initial effect of daprodustat to epoetin alfa after AC1 on Day 1. Change from pre-dose at each timepoint is calculated as measurement at post-dose minus pre-acute challenge 1 measurement.
Measured: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 hours post-dose
Plasma Concentrations of Daprodustat
Blood samples were collected at indicated time points for the concentrations of daprodustat.
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2391220
Blood samples were collected at indicated time points for the concentrations of metabolite GSK2391220.
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2506104
Blood samples were collected at indicated time points for the concentrations of metabolite GSK2506104.
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2487818
Blood samples were collected at indicated time points for the concentrations of metabolite GSK2487818.
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2506102
Blood samples were collected at indicated time points for the concentrations of metabolite GSK25206102.
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2531398
Blood samples were collected at indicated time points for the concentrations of metabolite GSK2531398.
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2531401
Blood samples were collected at indicated time points for the concentrations of metabolite GSK2531401.
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Maximum Plasma Concentration (Cmax) of Daprodustat, GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401
Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat and its metabolites GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Time of Occurrence of Cmax (Tmax) of Daprodustat, GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401
Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat and its metabolites GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Terminal Phase Half-life (t1/2) of Daprodustat, GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401
Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat and its metabolites GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Area Under Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Daprodustat, GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401
Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat and its metabolites GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2017 (estimated)
- Study start27 Jul 2017
- Primary completion9 Jul 2020
- Study completion9 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AnaemiaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ERT: Clinical Trial Technology Solutions, Q2 Solutions, Quintiles, Inc., HemoCue
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03029247
- Sponsor's protocol ID
- 205665
- Status last verified
- Jun 2021
- First submitted
- 20 Jan 2017
- Last updated
- 3 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
PubMed 36005278
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label Study to Evaluate the Effect of Daprodustat on Blood Pressure in Subjects With Anemia Associated With Chronic Kidney Disease on Hemodialysis Switched From a Stable Dose of an Erythropoiesis-stimulating Agent
- ClinicalTrials.gov ID
- NCT03029247
- Acronym / sponsor ID
- 205665
- Conditions
- Anaemia
- Keywords
- Anemia, Daprodustat, Blood pressure, ESA, CKD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Collaborators
- ERT: Clinical Trial Technology Solutions, Q2 Solutions, Quintiles, Inc., HemoCue
- Study start
- 27 Jul 2017 (actual)
- Primary completion
- 9 Jul 2020 (actual)
- Study completion
- 9 Jul 2020 (actual)
- First posted
- 24 Jan 2017 (estimated)
- Results
- Posted 3 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be an open-label, randomized, parallel-group study in hemodialysis-dependent (HD) participants with anemia associated with chronic kidney disease (CKD), designed to compare the effects of daprodustat to epoetin alfa on blood pressure (BP). Participants will be screened for eligibility within 7 and 30 days prior to erythropoesis-stimulating agent (ESA) washout. Following a 2-week ESA washout period, on Day 1 participants will be randomized 1:1 and stratified by prior ESA dose before they undergo Acute Challenge 1, a single dose challenge to compare the acute effects on BP of the highest planned once-daily maintenance dose of daprodustat (24 milligrams [mg]) to the highest starting dose of epoetin alfa (100 units/kilogram [U/kg]). This will be followed by an 8-week hemoglobin (Hgb)-maintenance period, where doses of either daprodustat or epoetin alfa will be administered and adjusted. At the end of Hgb maintenance period, on Day 57 an Acute Challenge 2 will be repeated utilizing the same treatment dose administered in Acute Challenge 1; there will be a follow-up visit within 14+/-3 days after completing treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Participants receiving Epoetin alfa | Active comparator | Drug: Epoetin alfaOn Day 1, participants will undergo 24-hour Acute Challenge 1, in which participants will receive a single dose of 100 U/kg epoetin alfa IV. After completing Acute Challenge 1, participants will enter in an 8-week Hgb maintenance period. At the end of Hgb maintenance period, on Day 57, Acute Challenge 2 will be performed utilizing the same treatment dose administered in Acute Challenge 1. |
| Participants receiving Daprodustat | Experimental | Drug: DaprodustatOn Day 1, participants will undergo 24-hour Acute Challenge 1, in which participants will receive 24 mg daprodustat. After completing Acute Challenge 1, participants will enter an 8-week Hgb maintenance period. At the end of Hgb maintenance period, on Day 57, Acute Challenge 2 will be performed utilizing the same treatment dose administered in Acute Challenge 1. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- More than or equal to 40 years of age, at the time of signing the informed consent
- Stable Hgb 8.5 to 11.5 grams per deciliter (g/dL) inclusive.
- Dialysis frequency: On hemodialysis (HD, hemofiltration or hemodiafiltration) three-to five-times weekly for at least 4 weeks prior to screening.
- A single pool Kt/Vurea >=1.2 based on a historical value obtained within 3 months prior to screening in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio should be at least 65 percent (%).
- Treated with an ESA (epoetins or their biosimilars, darbepoetin, or methoxy polyethylene glycol [PEG]-epoetin beta) for at least 4 weeks prior to screening.
Key exclusion criteria (29 listed)
- Planned change from HD to peritoneal dialysis within the study time period, or on home dialysis.
- Planned for kidney transplant within the 16 weeks following the Screening visit.
- An epoetin alfa dose of >=360 U/kg/week IV or >=250 U/kg/week subcutaneous (SC), or darbepoetin dose of >=1.8 micrograms (μg)/kg/week IV or SC, or methoxy PEG-epoetin beta dose of >=2.2 μg/kg/week within the 8 weeks prior to screening through Week -4.
- Planned or recorded administration of Mircera (methoxy PEG-epoetin beta) within the 4 weeks prior to the Washout.
- Occurrence of myocardial infarction or acute coronary syndrome within 3 months prior to Washout.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaprodustatDaprodustat will be available as oral tablets at unit dose strength of 1, 2, 4, 6, 8 and 10 mg. | Drug | Participants receiving Daprodustat |
| Epoetin alfaEpoetin alfa will be administered according to local labelling and clinical practice guidelines to keep Hgb in the target range (10.0-11.0 g/dL) | Drug | Participants receiving Epoetin alfa |
Primary outcome
Average of Systolic Blood Pressure (SBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM) Over 6-hour Post Dosing on Day 57
Time frame: Up to 6 hours post dose on Day 57
The effect of daprodustat and epoetin alfa on blood pressure was compared using ABPM after 8 weeks of Hgb maintenace therapy on Day 57. Analysis was based on "analysis of covariance (ANCOVA) with terms for treatment, prior erythropoiesis-stimulating agent (ESA) dose (low/high), post-Hemodialysis dependent (HD)/pre-AC 1 SBP, difference between post-HD/pre-AC 2 SBP and post-HD/pre-AC 1 SBP and treatment by difference in post-HD SBP between AC 1 and 2 interaction." Least square (LS) mean of 6 hour average SBP post AC2 on Day 57 and its corresponding standard error has been presented.
21 secondary outcomes
Average of SBP, Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) Measured by ABPM Over 6-hour Post Dosing on Day 1
Time frame: Up to 6 hours post dose on Day 1
Average of Heart Rate (HR) Measured by ABPM Over 6 Hour Post Dosing on Day 1
Time frame: Up to 6 hours post dose on Day 1
Area Under the Effect Curve (AUEC) of SBP, DBP and MAP Measured by ABPM Over 24-hour Post Dosing on Day 1
Time frame: Up to 24 hours post dose on Day 1
AUEC of HR Measured by ABPM Over 24-hour Post Dosing on Day 1
Time frame: Up to 24 hours post dose on Day 1
Average of DBP and MAP Measured by ABPM Over 6-hour Post Dosing on Day 57
Time frame: Up to 6 hours post dose on Day 57
Average of HR Measured by ABPM Over 6 Hour Post Dosing on Day 57
Time frame: Up to 6 hours post dose on Day 57
AUEC of SBP, DBP and MAP Measured by ABPM Over 24-hour Post Dosing on Day 57
Time frame: Up to 24 hours post dose on Day 57
AUEC of HR Measured by ABPM Over 24-hour Post Dosing on Day 57
Time frame: Up to 24 hours post dose on Day 57
Change From Pre-dose in SBP, DBP and MAP at Day 1
Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 hours post-dose
Change From Pre-dose in HR at Day 1
Time frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 hours post-dose
Plasma Concentrations of Daprodustat
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2391220
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2506104
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2487818
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2506102
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2531398
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2531401
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Maximum Plasma Concentration (Cmax) of Daprodustat, GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Time of Occurrence of Cmax (Tmax) of Daprodustat, GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Terminal Phase Half-life (t1/2) of Daprodustat, GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Area Under Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Daprodustat, GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36005278Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daprodustat and Epoetin alfa in people with Anaemia, run by GlaxoSmithKline at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average of Systolic Blood Pressure (SBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM) Over 6-hour Post Dosing on Day 57 (time frame: Up to 6 hours post dose on Day 57). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03029247, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2021.