A clinical trial to study the effects of two drugs, daprodustat and recombinant human erythropoietin (rhEPO ) in subjects with anemia associated with chronic kidney disease who are initiating dialysis.
- Conditions
- Health Condition 1: null- anemia associated with chronic kidney disease (CKD) in subjects who are planning to start or who have recently started dialysis.Health Condition 2: D631- Anemia in chronic kidney disease
- Registration Number
- CTRI/2018/04/013108
- Lead Sponsor
- GlaxoSmithKline Research Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
1. 18 to 99 years of age inclusive.
2. Planning to start chronic dialysis within the next 6 weeks (from the date of the screening visit) OR have started and received dialysis (as specified below) for end-stage renal disease for a maximum of less than or equal to 90 days immediately prior to randomization and is not expected to stop dialysis during the duration of the trial: HD is greater than or equal to 2 times per week or PD greater than or equal to 4 times per week including incremental schedule; subjects on continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) are eligible.
3. Hemoglobin concentration as measured by HemoCue (range inclusive): 8 to 10.5 g/dL (5-6.5 millimoles per liter [mmol/L]) at screening and 8-11.0 g/dL (5 to 6.8 mmol/L) at randomization.
4. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
1.ESA:
-Use of ESA treatment within 8 weeks prior to screening except for limited use as part of dialysis initiation.
-Limited use allowed of no more than 6 weeks before or after starting dialysis of the following: of short-acting ESA (rhEPO or biosimilars; max. 20000 U total)
or long-acting ESA -darbepoetin alfa (max. 100 µg total) or methoxy polyethylene glycol-epoetin beta (max. 125 µg total)
2. CKD related:
- Planned living-related (and unrelated) kidney transplant during the study
3. Anemia related:
- Ferritin (screening or after IV iron supplementation): =100 ng/mL (=100 mcg/L)
- Transferrin saturation (TSAT) (screening or after IV iron supplementation): =20%
- Folate (screening only): <2.0 ng/mL ( <4.5 nmol/L)
- Vitamin B12 (screening or after vitamin B12): below the lower limit of reference range
- Aplasias: History of bone marrow aplasia or pure red cell aplasia (PRCA)
- Other causes: Pernicious anemia, thalassemia major, sickle cell disease or myelodysplastic syndrome
- Gastrointestinal (GI) bleeding (evidence of ulcers OR clinically significant GI bleeding =10 weeks prior to study)
4. Cardiovascular disease related:
- MI or ACS, Stroke or TIA =10 weeks prior to study; chronic Class IV heart failure (defined by NYHA); Current uncontrolled hypertension (preclude ESA use)
- Day 1: QTcB >500 msec or QTcB >530 msec in subjects with bundle branch block. There is no QTc exclusion for subjects with a predominantly ventricular paced rhythm.
5. Other disease related:
-Liver: ALT >2x upper limit of normal (ULN) & bilirubin >1.5xULN; Current unstable or severe active liver or biliary disease
- History of malignancy within the two years prior to screening or currently receiving treatment for cancer, or known complex kidney cyst (i.e. Bosniak Category II F, III or IV) > 3cm.
6. Concomitant medication and other study treatment related criteria:
- Severe allergic reactions to daprodustat or rhEPO comparator.
- Strong inhibitor of CYP2C8 (e.g., gemfibrozil) or strong inducers of CYP2C8 (e.g., rifampin /rifampicin).
- Participation in other investigational agent/device study
- Any prior treatment with daprodustat for > 30 days.
7. Other:
- Pregnancy or lactation; other conditions
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method