Anemia, Renal Insufficiency, Chronic
Conditions
Keywords
Anemia of CKD on dialysis
Brief summary
Evaluate efficacy and safety of 16 weeks of titrated dose treatment with BAY85-3934 versus epoetin alfa/beta as measured by hemoglobin (Hb) levels. Fixed starting doses of 25, 50,75 and 150 mg of BAY85-3934 titrated at the scheduled dose control visits. Titration will be based on the subject's Hb response and tolerability of the prior dose. Planned doses include 15, 25, 50, 75, 100,150 and 200 mg/day
Interventions
DRUGMolidustat (BAY 85-3934)
Oral doses of BAY85-3934 will be available in multiples of 25,50,75 and 150 mg tablets
BIOLOGICALEpoetin alfa/beta
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \- Eligible subjects will have a diagnosis of anemia associated with CKD(chronic kidney disease). * Women without childbearing potential * Male or female subject ≥ 18 years of age with anemia of CKD at screening * On dialysis, defined as regular long-term hemodialysis, with the same modality of dialysis for ≥ 3 months before randomization * Dialysis vascular access via native arteriovenous fistula, synthetic graft, long-term catheters, or long-term tunneled catheters * Treated with epoetin alfa (US or Japan) or epoetin beta (Japan) via intravenous (IV) or subcutaneous (SC) route, on stable dosing defined as a \< 50% change from the maximum prescribed weekly dose with no change in the prescribed frequency during the last 8 weeks prior to randomization * At least one kidney * Mean screening Hb concentration 9.0 to 11.5 g/dL inclusive (mean of all local laboratory Hb measurements \[at least 2 measurements must be taken ≥ 2 days apart\] during the 4 week screening period, AND none of the measurements can be \< 9.0 g/dL or \> 12.0 g /dL * Serum ferritin levels ≥ 100 μg/L OR transferrin saturation ≥ 20% at screening. Iron substitution is allowed * Folate and vitamin B12 levels above the lower limit of normal. Supplementation is allowed *
Exclusion criteria
* Subjects with significant acute or chronic bleeding, such as overt gastrointestinal bleeding * Hereditary hemoglobinopathies (including, but not limited to, sickle cell disease, beta thalassemia, and thalassemia major) which may be the primary cause of anemia * Chronic lymphoproliferative diseases * Any allograft (including renal allograft) in place and on immunosuppressive therapy, or a scheduled kidney transplant within the next 16 weeks (being on a waiting list does not exclude the subject) * Chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) * Subjects treated with immuno- or myelosuppressive therapy within 8 weeks prior to randomization: e.g., everolimus, sirolimus, rituximab, azathioprine, mycophenolate mofetil, mycophenolic acid, cyclosporine,methotrexate, and tacrolimus, chemotherapeutic agents and other anticancer agents, and systemic steroids (except inhaled steroids) for 7 days * RBC-containing transfusion within 8 weeks before randomization * History of cardio- (cerebro-) vascular events (e.g., unstable angina, myocardial infarction, stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism) within the last 6 months from the initial screening visit * Sustained, poorly controlled arterial hypertension or hypotension at screening, defined as a mean BP ≥ 180/110 mmHg or systolic BP \< 95 mmHg, respectively * Severe rhythm or conduction disorder (e.g., HR \< 50 or \> 110 bpm, atrial flutter, prolonged QT \>500 msec, second or third degree atrioventricular \[AV\]block if not treated with a pacemaker) * New York Heart Association Class III or IV congestive heart failure * Severe hepatic insufficiency (defined as alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], or gamma-glutamyl transferase \> 3 times the upper limit of normal \[ULN\], total bilirubin \> 2 mg/dL, or Child-Pugh B or C) or active hepatitis in the investigator's opinion * A scheduled surgery that may be expected to lead to significant blood loss
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in local laboratory hemoglobin level from baseline to the average during the last 4 weeks treatment period | Baseline and weeks 14 to 17 |
Secondary
| Measure | Time frame |
|---|---|
| Mean of the hemoglobin levels in the target range (9.5 to 11.5 g/dL) | From week 14 to 17 |
| Change from baseline in Hb during active treatment | Baseline and weeks 14 to 17 |
| Number of patients with hemoglobin levels outside the target range | From week 14 to 17 |
| Mean of the hemoglobin (Hb) levels in the target range (10.0 to 11.0 g/dL) | From week 14 to 17 |
| Duration of exposure on each dose level | Up to 16 weeks |
| Number of subjects requiring titration of dose | Up to 16 weeks |
| Number of participants with serious adverse events as a measure of safety and tolerability | Up to 16 weeks |
| Dose level in the evaluation period | Up to 16 weeks |
Countries
Japan, United States
Outcome results
None listed