Clinical Trial Details

NCT ID: NCT03029247
Date Last Changed: September 25, 2017

Overview

Research Study Summary

A clinical trial seeking patients for a research study for the treatment of Anaemia

Research Study 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

Purpose

This will be an open-label, randomized, parallel-group study in hemodialysis-dependent (HD) subjects with anemia associated with chronic kidney disease (CKD), designed to compare the effects of daprodustat to epoetin alfa on blood pressure (BP).

After a 4-week screening and a 4-week erythropoesis-stimulating agent (ESA) washout period, on Day 1 subjects 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 international units [IU]/kilograms [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 (number 2) will be repeated utilizing the same treatment as of Acute Challenge 1; there will be a follow-up visit within 14+/-3 days after completing treatment. The total duration of subject involvement is up to 18 weeks (Screening to Follow-up).

To Learn more

Recruitment Details

Phase
2
Gender
All
Age
40 and up
Overall Status
Recruiting
Lead Sponsor
GlaxoSmithKline
Duration
10 Months
Facility Type
N/A
Compensation

Eligibility

All ages 40 Years and up

Inclusion Criteria

  • More than or equal to 40 years of age, at the time of signing the informed consent

  • Stable Hgb 9.0 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%.

  • Treated with the same ESA (epoetins or their biosimilars, darbepoetin, or methoxy polyethylene glycol [PEG]-epoetin beta) with total weekly dose varying by not > 50% during the 4 weeks prior to screening.

  • Subjects may be on stable maintenance oral or intravenous (IV; < =100 mg/week) iron supplementation. If subjects are on oral or IV iron, then doses must be stable for the 4 weeks prior to screening through Day 1.

  • Estimated Dry Weight: Mid-week average weight gain between dialysis treatments < 5% as assessed pre- and post-dialysis from screening to Day 1.

  • On at least 2 different antihypertensive medications of different classes and on a stable dose and number of hypertensive medications for the 4 weeks prior to screening through Day 1.

  • 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

Exclusion Criteria

  • Planned change from HD to peritoneal dialysis within the study time period, or on home dialysis.

  • Planned for kidney transplant within the 18 weeks following the Screening visit.

  • An epoetin alfa dose of > =360 International units (IU)/Kilograms (kg)/week IV or > =250 IU/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.

  • Administration of Mircera (methoxy PEG-epoetin beta) within the 4 weeks prior to screening through Week -4.

  • Occurrence of myocardial infarction or acute coronary syndrome within the 4 weeks prior to screening through Day 1.

  • Stroke or transient ischemic attack within the 4 weeks prior to screening through Day 1.

  • Chronic Class IV heart failure, as defined by the New York Heart Association functional classification system diagnosed prior to screening through Day 1.

  • QT interval corrected for heart rate using Bazett's formula (QTcB) > 500 milliseconds (msec), or QTcB > 530 msec in subjects with Bundle Branch Block. There is no QTc exclusion for subjects with a predominantly paced rhythm.

  • Resting SBP > 160 millimeter of mercury (mmHg); or DBP > 100 mmHg at screening.

  • Presence of atrial fibrillation or a history of atrial fibrillation

  • Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosus, rheumatoid arthritis, celiac disease) diagnosed prior to screening through Day 1.

  • History of bone marrow aplasia or pure red cell aplasia.

  • Other causes of anemic including Pernicious anemia, thalassemia major, sickle cell disease or myelodysplastic syndrome.

  • Alanine transaminase (ALT) > 2x upper limit of normal (ULN) (screening only) or Bilirubin > 1.5xULN (screening only) or Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.

  • Major surgery (excluding vascular access surgery) within the 8 weeks prior to screening through Day 1, or planned during the study.

  • Blood transfusion within the 8 weeks prior to screening through Day 1, 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 4 weeks prior to screening through Day 1.

  • Clinical evidence of acute infection or history of infection requiring IV antibiotic therapy within the 4 weeks prior to Screening through Day 1.

  • 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.

  • Subjects 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 Day 1.

  • The subject has participated in a clinical trial and has received an experimental investigational product within the 30 days prior to screening through Day 1.

  • Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject 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 subject is pregnant (as confirmed by a positive serum human chorionic gonadotrophin test for females of reproductive potential only), subject is breastfeeding, or subject 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).

  • Folate at < 2.0 nanograms (ng)/milliliter (mL) (4.5 Nanomoles/L) (may rescreen in a minimum of 4 weeks).

  • Ferritin at < 100 ng/mL

  • Transferrin saturation at < 20%.

Site Locations (1)

Country State City Zip Facility and Contact
United States California La Mesa 91942 GSK Investigational Site
US GSK Clinical Trials Call Center
877-379-3718
GSKClinicalSupportHD@gsk.com

Contact

US GSK Clinical Trials Call Center
877-379-3718
E-mail:

DISCLAIMER: CenterWatch does not conduct clinical research. CenterWatch is a publishing company that posts clinical trials information on behalf of sponsor companies, contract research organizations, clinical research sites and other interested parties. This information is designed to help patients find clinical trials of interest and contact the research centers conducting the trials.