Anemia in chronic kidney disease patients with dialysis MedDRA version: 17.1 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 100000004857
Conditions
Interventions
Product Name: roxadustat
Product Code: AZD9941
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: roxadustat
CAS Number: 80811
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age > or = 18 years - Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease at least 30 days prior to visit 1. - Two central laboratory Hb values during the screening period, obtained at least 7 days apart, must be or = 100 ng/mL at randomization. - Transferrin saturation (TSAT) > or = 20% at randomization. - Serum folate level > or = lower limit of normal (LLN) at randomization. - Serum vitamin B12 level > or = LLN at randomization. - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =65 years) yes F.1.3.1 Number of subjects for this age range 700
Exclusion criteria
Exclusion criteria: - New York Heart Association Class III or intravenous (IV) congestive heart failure at enrollment - Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization. - History of chronic liver disease (e.g., chronic infectious hepatitis, chronic autoimmune liver disease, cirrhosis or fibrosis of the liver). - Known hereditary hematologic disease such as thalassemia, sickle cell anemia, a history of pure red cell aplasia or other known causes for anemia other than chronic kidney disease (CKD). - Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis). - Diagnosis or suspicion (e.g. complex kidney cyst of Bosniak Category IIF, III or IV) of renal cell carcinoma on renal ultrasound (or other imaging procedure e.g. computerized tomography (CT) scan or magnetic resonance imaging (MRI)) conducted at screening or within 12 weeks prior to randomization. - Uncontrolled hypertension at the time of randomization, (defined as systolic BP > or =180 mmHg or diastolic BP > or =100 mmHg on repeated measurement post-dialysis in hemodialysis patients or at any time in peritoneal dialysis patients), contraindication to epoetin alfa treatment (e.g., pure red cell aplasia, hypersensitivity or know inability to tolerate epoetin alfa). - History of prostate cancer, breast cancer or any other malignancy, except the following: cancers determined to be cured or in remission for > or = 5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ or resected colonic polyps. - Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibody. - Chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ankylosing spondylitis, psoriatic arthritis or inflammatory bowel disease that is determined to be principal cause of anemia. - Known hemosiderosis, hemochromatosis or hypercoagulable condition. - Any prior organ transplant with the exception of a renal transplant that was subsequently removed (?explanted?) or scheduled organ transplantation date. - Any red blood cell (RBC) transfusion during the screening period. - Any current condition leading to active significant blood loss. - Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). - History of alcohol or drug abuse within 2 years prior to randomization - Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence. - Pregnant or breastfeeding females. - Known allergy to the investigational product or any of its ingredients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the cardiovascular (CV) safety of roxadustat based on comparison with epoetin alfa for the composite endpoint of all cause mortality, non-fatal myocardial infarction and non-fatal stroke;Primary end point(s): Major adverse cardiovascular (CV) events (MACE): Time to first occurrence of death from any cause, non-fatal myocardial infarction or non-fatal stroke.;Timepoint(s) of evaluation of this end point: From randomization (week 0) to end of study (event-driven, anticipate 1-2 years).; Secondary Objective: Evaluate the efficacy of roxadustat as compared to epoetin alfa Evaluate the CV safety of roxadustat based on comparison with epoetin alfa for the composite endpoint of all cause mortality, non-fatal myocardial infarction, non-fatal stroke, heart failure requiring hospitalization and unstable angina leading to hospitalization Evaluate the CV safety of roxadustat based on comparison with epoetin alfa for the composite safety endpoint (CSE) of all cause mortality, non-fatal myocardial infarction, non-fatal stroke, heart failure leading to hospitalization, unstable angina requiring hospitalization, vascular access thrombosis, deep vein thrombosis, pulmonary embolism or hypertensive emergency. Evaluate the need for rescue therapy in patients treated with roxadustat as compared to epoetin alfa Evaluate self-reported health status in patients treated with roxadustat as compared to epoetin alfa To assess the safety and tolerability of roxadustat as compared to epoetin alfa | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Mean change in hemoglobin (Hb) from baseline to the end of treatment period (event-driven, anticipate 1-2 years). 2. Proportion of total time of Hb measurements within the interval of 11±1 g/dL from week 28 until end of treatment visit (event-driven, anticipate 1-2 years). 3. Major adverse CV events+ (MACE+): Time to first occurrence of death from any cause, non-fatal myocardial infarction (MI), non-fatal stroke, heart failure requiring hospitalization or unstable angina leading to hospitalization. 4. Time to first occurrence of death from any cause, non-fatal MI, non-fatal stroke, heart failure requiring hospitalization, unstable angina leading to hospitalization, vascular access thrombosis, deep vein thrombosis, pulmonary embolism or hypertensive emergency. 5. Time to first rescue therapy (composite of erythropoietin analogue therapy [for roxadustat-allocated patients only] or RBC transfusion). 6.Changes in self-reported health status as measured by the EuroQol Health Utility Index (EQ-5D-5L) during roxadustat or epoetin alfa treatment. Measured at baseline, week 12, 28 and 52. 7. Adverse events (AEs), serious adverse events (SAEs) Changes in vital signs, electrocardiogram (ECG) and laboratory values. Measured from the first screening visit to the end of the study (event-driven, anticipated duration 1-2 years). ; Timepoint(s) of evaluation of this end point: 1. From baseline to end of study (event-driven, anticipate 1-2 years). 2. From week 28 until end of study (event-driven, anticipate 1-2 years). 3. From randomization (week 0) to end of study (event-driven, anticipate 1-2 years). 4. From randomization (week 0) to end of study (event-driven, anticipate 1-2 years). 5. From randomization (week 0) to end of study (event-driven, anticipate 1-2 years). | — |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Czech Republic, Hungary, India, Mexico, Peru, Philippines, Poland, Romania, Russian Federation, Slovakia, Spain, Sweden, Thailand, Ukraine, United States, Vietnam
Contacts
Public ContactUnidad de Investigación Clínica
AstraZeneca Farmacéutica Spain, S.A.
Outcome results
None listed