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Anemia Study in Chronic Kidney Disease (CKD) : Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat -Forearm Blood Flow (ASCEND-FBF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03446612
Recruitment Status : Suspended (Due to the COVID-19 pandemic, this study has temporarily suspended recruitment activities. Other elements of the study are ongoing.)
First Posted : February 27, 2018
Last Update Posted : May 4, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Anaemia Drug: Daprodustat Drug: Darbepoetin alfa Drug: Acetylcholine Drug: Sodium nitroprusside Drug: L-N-monomethyl arginine acetate (L-NMMA) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomized to either daprodustat or darbepoetin alfa. A central randomization approach will be used with stratification by center.
Masking: None (Open Label)
Masking Description: This is an open-label study. However, a central FBF reader, who will read and evaluate the FBF data, will be blinded to the treatment assignment.
Primary Purpose: Treatment
Official Title: A Randomized, Repeat Dose, Open Label, Parallel Group, Multi-center Study to Evaluate the Effect of Daprodustat Compared to Darbepoetin Alfa on Forearm Blood Flow in Participants With Anemia of Chronic Kidney Disease That Are Not Dialysis Dependent
Actual Study Start Date : January 16, 2019
Estimated Primary Completion Date : March 28, 2022
Estimated Study Completion Date : March 28, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Participants receiving Daprodustat
Participants will receive 2 milligram (mg) daprodustat tablets once daily via oral route for a period of 41 days.
Drug: Daprodustat
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.

Drug: Acetylcholine
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.

Drug: Sodium nitroprusside
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.

Drug: L-N-monomethyl arginine acetate (L-NMMA)
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.

Active Comparator: Participants receiving Darbepoetin alfa
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
Darbepoetin alfa will be given as solution for injection for subcutaneous administration every 2 weeks.

Drug: Acetylcholine
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.

Drug: Sodium nitroprusside
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.

Drug: L-N-monomethyl arginine acetate (L-NMMA)
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.




Primary Outcome Measures :
  1. Change in FBF ratio from Day 1 to Day 42 in response to acetylcholine [ Time Frame: Day 1 to Day 42 ]
    Venous occlusion plethysmography will be used for FBF assessment. Acetylcholine will be infused intra-arterially at 7.5, 15 and 30 micrograms/minute each for 6 minutes per infusion. Measures will be made in both arms concurrently, and the maximal strain gauge measure from the infused arm will be divided by the same from the non-infused arm, producing a ratio.


Secondary Outcome Measures :
  1. Change in the absolute FBF from Day 1 to Day 42 in response to acetylcholine [ Time Frame: Day 1 to Day 42 ]
    Venous occlusion plethysmography will be used for FBF assessment. Acetylcholine will be infused intra-arterially at 7.5, 15 and 30 micrograms/minute each for 6 minutes per infusion. Measures will be made in both arms concurrently.

  2. Change in FBF ratio from Day 1 to 42 in response to sodium nitroprusside [ Time Frame: Day 1 to Day 42 ]
    Venous occlusion plethysmography will be used for FBF assessment. Sodium nitroprusside will be infused at 3 and 10 micrograms/minute each for 6 minutes per infusion into the brachial artery of the test arm. Measures will be made in both arms concurrently, and the maximal strain gauge measure from the infused arm will be divided by the same from the non-infused arm, producing a ratio.

  3. Change in the absolute FBF from Day 1 to Day 42 in response to sodium nitroprusside [ Time Frame: Day 1 to Day 42 ]
    Venous occlusion plethysmography will be used for FBF assessment. Sodium nitroprusside will be infused at 3 and 10 micrograms/minute each for 6 minutes per infusion into the brachial artery of the test arm. Measures will be made in both arms concurrently.

  4. Change in FBF ratio from Day 1 to Day 42 in response to NG-monomethyl arginine acetate(L-NMMA) [ Time Frame: Day 1 to Day 42 ]
    Venous occlusion plethysmography will be used for FBF assessment. Effects on basal nitric oxide synthesis will be assessed using L-NMMA at doses of 2 and 8 micromoles/minute each infused for 6 minutes into the brachial artery of the test arm. Measures will be made in both arms concurrently, and the maximal strain gauge measure from the infused arm will be divided by the same from the non-infused arm, producing a ratio.

  5. Change in the absolute FBF from Day 1 to Day 42 in response to L-NMMA [ Time Frame: Day 1 to Day 42 ]
    Venous occlusion plethysmography will be used for FBF assessment. Effects on basal nitric oxide synthesis will be assessed using L-NMMA at doses of 2 and 8 micromoles/minute each infused for 6 minutes into the brachial artery of the test arm. Measures will be made in both arms concurrently.

  6. Change in FBF ratio in response to challenge agent at Day 42 versus (vs) Day 1 in participants treated with daprodustat [ Time Frame: Day 1 and Day 42 ]
    Venous occlusion plethysmography will be used for FBF assessment. FBF will be conducted on Day 1 and Day 42. Challenge agents will include Acetylcholine, Sodium nitroprusside and L-NMMA. Acetylcholine will be infused intra-arterially at 7.5, 15 and 30 micrograms/minute each for 6 minutes per infusion. Sodium nitroprusside will be infused intra-arterially at 3 and 10 micrograms/minute each for 6 minutes per infusion. Effects on basal nitric oxide synthesis will be assessed using L-NMMA at doses of 2 and 8 micromoles/minute each infused for 6 minutes. Measures will be made in both arms concurrently, and thus the maximal strain gauge measure from the infused arm will be divided by the same from the contralateral (non-infused) arm, producing a ratio.

  7. Change in the absolute FBF in response to challenge agent at Day 42 vs Day 1 in participants treated with daprodustat [ Time Frame: Day 1 and Day 42 ]
    Venous occlusion plethysmography will be used for FBF assessment. FBF will be conducted on Day 1 and Day 42. Challenge agents will include Acetylcholine, Sodium nitroprusside and L-NMMA. Acetylcholine will be infused intra-arterially at 7.5, 15 and 30 micrograms/minute each for 6 minutes per infusion. Sodium nitroprusside will be infused intra-arterially at 3 and 10 micrograms/minute each for 6 minutes per infusion. Effects on basal nitric oxide synthesis will be assessed using L-NMMA at doses of 2 and 8 micromoles/minute each infused for 6 minutes. Measures will be made in both arms concurrently.

  8. Change in FBF ratio in response to challenge agent at Day 42 vs Day 1 in participants treated with darbepoetin alfa [ Time Frame: Day 1 and Day 42 ]
    Venous occlusion plethysmography will be used for FBF assessment. FBF will be conducted on Day 1 and Day 42. Challenge agents will include Acetylcholine, Sodium nitroprusside and L-NMMA. Acetylcholine will be infused intra-arterially at 7.5, 15 and 30 micrograms/minute each for 6 minutes per infusion. Sodium nitroprusside will be infused intra-arterially at 3 and 10 micrograms/minute each for 6 minutes per infusion. Effects on basal nitric oxide synthesis will be assessed using L-NMMA at doses of 2 and 8 micromoles/minute each infused for 6 minutes. Measures will be made in both arms concurrently, and thus the maximal strain gauge measure from the infused arm will be divided by the same from the contralateral (non-infused) arm, producing a ratio.

  9. Change in the absolute FBF in response to challenge agent at Day 42 vs Day 1 in participants treated with darbepoetin alfa [ Time Frame: Day 1 and Day 42 ]
    Venous occlusion plethysmography will be used for FBF assessment. FBF will be conducted on Day 1 and Day 42. Challenge agents will include Acetylcholine, Sodium nitroprusside and L-NMMA. Acetylcholine will be infused intra-arterially at 7.5, 15 and 30 micrograms/minute each for 6 minutes per infusion. Sodium nitroprusside will be infused intra-arterially at 3 and 10 micrograms/minute each for 6 minutes per infusion. Effects on basal nitric oxide synthesis will be assessed using L-NMMA at doses of 2 and 8 micromoles/minute each infused for 6 minutes. Measures will be made in both arms concurrently.

  10. Change in Augmentation index (AIx) from Day 1 to 42 [ Time Frame: Day 1 to Day 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 will be 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 is defined as the augmentation (difference between systolic peaks) expressed as a percentage of the overall pulse pressure.

  11. Change in pulse wave velocity (PWV) from Day 1 to Day 42 [ Time Frame: Day 1 to Day 42 ]
    PWV will be assessed with a high-fidelity micro manometer which will be 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.


Other Outcome Measures:
  1. Number of participants with any adverse events (AE) [ Time Frame: Up to 59 days ]
    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.

  2. Number of participants with any AE by severity [ Time Frame: Up to 59 days ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  3. Number of participants with any serious adverse events (SAE) [ Time Frame: Up to 59 days ]
    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.

  4. Number of participants with any AE of special interest (AESI) [ Time Frame: Up to 59 days ]
    AESI will be assessed and number of participants with AESI will be reported.

  5. Number of participants discontinuing the randomized study treatment [ Time Frame: Up to Day 42 ]
    Number of participants discontinuing randomized study treatment due to specific reasons will be analyzed.

  6. Absolute values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) [millimeter of mercury (mmHg)] [ Time Frame: Up to 59 days ]
    Blood pressure will be assessed in a semi-supine position with a completely automated device. Three consecutive blood pressure readings will be recorded at intervals of at least 1 minute. The average of the 3 blood pressure readings will be recorded.

  7. Change from Baseline in SBP and DBP (mmHg) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Blood pressure will be assessed in a semi-supine position with a completely automated device. Three consecutive blood pressure readings will be recorded at intervals of at least 1 minute. The average of the 3 blood pressure readings will be recorded.

  8. Absolute values of heart rate (Beats per minute) [ Time Frame: Up to 59 days ]
    Heart rate will be recorded with the participant in a semi-supine position.

  9. Change from Baseline in heart rate (Beats per minute) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Heart rate will be recorded with the participant in a semi-supine position.

  10. Absolute values of electrocardiogram (ECG) parameters- PR interval, QRS interval, and QT (uncorrected) interval and QT interval corrected for heart rate using Bazett's formula (QTcB) (Milliseconds) [ Time Frame: Up to 59 days ]
    Full 12-lead ECGs will be recorded with the participant in a semi-supine position. PR interval, QRS duration, and QT (uncorrected) interval and QTcB will be measured.

  11. Change from Baseline in ECG parameters- PR interval, QRS duration, and QT (uncorrected) interval and QTcB (Milliseconds) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Full 12-lead ECGs will be recorded with the participant in a semi-supine position. PR interval, QRS duration, and QT (uncorrected) interval and QTcB will be measured.

  12. Absolute values of the hematology parameters of platelet count, white blood cell (WBC) count (Absolute), basophils, eosinophils, lymphocytes, monocytes and neutrophils (Giga cells per Liter) [ Time Frame: Up to 59 days ]
    Blood samples will be collected to measure platelet count, WBC count (Absolute), basophils, eosinophils, lymphocytes, monocytes and neutrophils.

  13. Change from Baseline in hematology parameters of platelet count, WBC count (Absolute), basophils, eosinophils, lymphocytes, monocytes and neutrophils (Giga cells per Liter) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Blood samples will be collected to measure platelet count, WBC count (Absolute), basophils, eosinophils, lymphocytes, monocytes and neutrophils.

  14. Absolute values of the hematology parameter of red blood cell (RBC) count and reticulocyte count (RC) (Trillion cells per liter) [ Time Frame: Up to 59 days ]
    Blood samples will be collected to measure RBC count and RC.

  15. Change from Baseline in hematology parameters of RBC count and RC (Trillion cells per liter) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Blood samples will be collected to measure RBC count and RC.

  16. Absolute values of the hematology parameters of hemoglobin and Mean Corpuscle Hemoglobin concentration (MCHC) [Grams per Liter (g/L)] [ Time Frame: Up to 59 days ]
    Blood samples will be collected to measure Hemoglobin and MCHC.

  17. Change from Baseline in hematology parameters- Hemoglobin and MCHC (g/L) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Blood samples will be collected to measure Hemoglobin and MCHC.

  18. Absolute values of hematology parameter of hematocrit (Proportion of red blood cells in blood) [ Time Frame: Up to 59 days ]
    Blood samples will be collected to measure hematocrit.

  19. Change from Baseline in hematology parameter of hematocrit (Proportion of red blood cells in blood) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Blood samples will be collected to measure hematocrit.

  20. Absolute values of hematology parameter of red blood cell distribution width (RDW) (Percentage of width) [ Time Frame: Up to 59 days ]
    Blood samples will be collected to measure RDW.

  21. Change from Baseline in RDW (Percentage of width) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Blood samples will be collected to measure RDW.

  22. Absolute values of the hematology parameter of mean corpuscular hemoglobin (MCH) (Picograms) [ Time Frame: Up to 59 days ]
    Blood samples will be collected to measure MCH.

  23. Change from Baseline in hematology parameter of MCH (Picograms) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Blood samples will be collected to measure MCH.

  24. Absolute values of the hematology parameter of mean corpuscular volume (MCV) (Femtoliters) [ Time Frame: Up to 59 days ]
    Blood samples will be collected to measure MCV.

  25. Change from Baseline in hematology parameter of MCV (Femtoliters) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Blood samples will be collected to measure MCV.

  26. Absolute values of clinical laboratory parameters of sodium, potassium, carbon-dioxide (total), chloride, glucose and urea (Millimoles per Liter) [ Time Frame: Up to 59 days ]
    Blood samples will be collected to measure sodium, potassium, carbon-dioxide (total), chloride, glucose and urea.

  27. Change from Baseline in clinical laboratory parameters of sodium, potassium, carbon-dioxide (total), chloride, glucose and urea (Millimoles per Liter) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Blood samples will be collected to measure sodium, potassium, carbon-dioxide (total), chloride, glucose and urea.

  28. Absolute values of clinical laboratory parameters of creatinine and bilirubin (direct/indirect and total) (Micromoles per liter) [ Time Frame: Up to 59 days ]
    Blood samples will be collected to measure creatinine and bilirubin (direct/indirect and total).

  29. Change from Baseline in clinical laboratory parameters of creatinine and bilirubin (direct/indirect and total) (Micromoles per liter) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Blood samples will be collected to measure creatinine and bilirubin (direct/indirect and total).

  30. Absolute values of clinical laboratory parameters of Alanine transaminase (ALT), Alkaline Phosphatase (ALP) and Aspartate transaminase (AST) (International units per Liter) [ Time Frame: Up to 59 days ]
    Blood samples will be collected to measure ALT, ALP and AST.

  31. Change from Baseline in clinical laboratory parameters of ALT, ALP and AST (International units per Liter) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Blood samples will be collected to measure ALT, ALP and AST.

  32. Absolute values of clinical laboratory parameters of Albumin (g/L) [ Time Frame: Up to 59 days ]
    Blood samples will be collected to measure Albumin.

  33. Change from Baseline in clinical laboratory parameters of Albumin (g/L) [ Time Frame: Baseline (Day 1) and up to Day 59 ]
    Blood samples will be collected to measure Albumin.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant must be at least 18 years of age inclusive, at the time of signing the informed consent.
  • Participants who are Stage 3, 4 or 5 CKD defined by estimated Glomerular Filtration Rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
  • Hemoglobin as measured by HemoCue at screening visit and Day 1 is <=11.0 grams/deciliter (g/dL) [<=110 gram/Litre (g/L)].
  • Palpable brachial artery as assessed at screening.
  • Participants, if necessary may be on stable maintenance oral iron supplementation (<50% change in overall dose and compliance of 80% of prescribed doses in the 4 weeks prior to and including the screening period). If participants have been on intravenous (IV) iron, then participants will not have received IV iron for 4 weeks prior to the Day 1 visit.
  • Male or female participants will be included.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who has been on an approved form of contraceptive for the 4 weeks prior to Day 1 and agrees to follow the contraceptive guidance until the Follow-up visit.
  • Capable of giving signed informed consent.

Exclusion Criteria:

  • On dialysis or clinical evidence of impending need to initiate dialysis within 12 weeks of Day 1.
  • Planned kidney transplant within 12 weeks of Day 1.
  • Presence of an arteriovenous (AV) fistula.
  • Recombinant human erythropoietin use within the 12 weeks prior to the screening visit and through Day 1.
  • History of severe allergic or anaphylactic reactions or hypersensitivity to the study treatment or challenge agents, or excipients in the study treatments or challenge agents.
  • Planned use of any prescription or non-prescription drugs or dietary supplements that are prohibited from screening until all assessments on Day 42 have been successfully completed.
  • The participant has participated in a clinical trial and has received an experimental investigational product within the prior 30 days or within 5 half-lives of the investigational product (whichever is longer) prior to screening and through Day 1.
  • At or below the lower limit of the reference range at screening for Vitamin B12 (may rescreen in a minimum of 8 weeks).
  • Ferritin <=50 nanograms/milliliter [<=50 microgram/liter (µg/L)] at screening.
  • Transferrin saturation (TSAT) <=15% (0.15) at screening.
  • Folate <2.0 nanogram/milliliter (4.5 nanomoles/liter; may rescreen in a minimum of 8 weeks) at screening.
  • High sensitivity C-reactive protein (hs-CRP) >=50 micrograms/milliliter (>=50 mg/L) at screening.
  • Myocardial infarction or acute coronary syndrome <=12 weeks prior to screening and through Day 1.
  • Hospitalization for greater than 24 hours <=12 weeks prior to screening and through Day 1.
  • Stroke or transient ischemic attack <=12 weeks prior to screening and through Day 1.
  • Class 4 heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
  • Resting SBP >180 millimeters of mercury (mmHg) or DBP >110 mmHg at screening visit or current uncontrolled hypertension as determined by the investigator.
  • 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 corrected QT (QTc) exclusion for participants with a predominantly ventricular paced rhythm.
  • Active chronic inflammatory disease that could impact erythropoiesis.
  • History of bone marrow aplasia or pure red cell aplasia.
  • Conditions, other than anemia of CKD, which can affect erythropoiesis.
  • Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal bleeding from <=8 weeks prior to screening and through Day 1.
  • ALT >2 times upper limit of normal (ULN; screening only).
  • Bilirubin >1.5 times ULN (screening only); Isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Major surgery within the 12 weeks prior to screening and through Day 1, or planned during the study.
  • Anticipated or planned vascular access surgery (i.e., arteriovenous [AV] fistula) within the 12 weeks prior to screening and through the Day 42 assessments.
  • Received a tissue heart valve replacement or repair within the 6 months prior to screening or has received a mechanical heart valve replacement.
  • Blood transfusion within 6 weeks prior to screening and through Day 1, or an anticipated need for blood transfusion during the study.
  • Clinical evidence of an acute infection, or history of infection requiring IV antibiotic therapy from 8 weeks prior to screening and through Day 1. Prophylactic oral antibiotics are allowed.
  • History of malignancy within the two years prior to screening and through Day 1 or currently receiving treatment for cancer, with the exception of localized squamous cell or basal cell carcinoma of the skin definitively treated 12 weeks prior to Day 1.
  • Platelet count <50,000/µL (<50 Giga cells per liter).
  • History of a bleeding disorder (e.g., hemophilia).
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03446612


Locations
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United Kingdom
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
GSK Investigational Site
Edinburgh, United Kingdom, EH16 4TJ
GSK Investigational Site
London, United Kingdom, SE1 7EH
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03446612    
Other Study ID Numbers: 205767
2017-002268-42 ( EudraCT Number )
First Posted: February 27, 2018    Key Record Dates
Last Update Posted: May 4, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints 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.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
darbepoetin alpha
challenge agents
daprodustat
FBF-CKD
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Anemia
Hematologic Diseases
Urologic Diseases
Renal Insufficiency
Nitroprusside
Acetylcholine
Darbepoetin alfa
omega-N-Methylarginine
Hematinics
Antihypertensive Agents
Vasodilator Agents
Nitric Oxide Donors
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs