15141 Fixed Dose Correction / naïve and Pre Dialysis (Europe and Asia Pacific)

Study Overview
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Brief Summary
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Anaemia is a condition in which blood has a lower than normal number of red blood cells. It can also occur if red blood cells do not contain enough haemoglobin, an oxygen carrying part of blood. Anaemia is common in patients with chronic kidney disease. Healthy kidneys produce a hormone called erythropoietin, which stimulates the bone marrow to produce the proper number of red blood cells needed to carry oxygen to vital organs. Chronic kidney disease is a general term that means that the kidneys are not functioning to their full potential. The study drug, BAY85-3934, is being evaluated as a drug to increase the body's ability to produce erythropoietin. The purpose of this study is to find out if the study drug, a tablet taken orally, is safe and effective for the treatment of anaemia associated with chronic kidney disease. The study will enroll 120 patients at multiple locations in Europe, Asia and Australia. Participation will involve a screening visit and between 12 and 14 study visits scheduled over a period of approximately 5 to 7 months. The estimated total duration of study treatment will be 16 weeks. During these scheduled visits patients will undergo a number of procedures to confirm efficacy and safety of the study drug, including measurement of heart rate and blood pressure, physical examination, Electrocardiogram and blood/urine sample collection for laboratory tests. The study will be conducted at 5 hospitals in the UK. Bayer HealthCare AG is funding this research.

Official Title
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A Randomized, Placebo-controlled, Double-blind, Parallel Group, Multicenter Study to Investigate the Efficacy and Safety of 5 Fixed Doses of BAY85-3934 Administered Orally in the Correction of Anemia in Pre-dialysis Subjects With Chronic Kidney Disease Not Currently Treated With Erythropoiesis-stimulating Agent in Europe and Asia Pacific

Conditions
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Anemia, Renal Insufficiency, Chronic

Intervention / Treatment
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* Drug: BAY85-3934
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women without childbearing potential Male or female subjects ≥ 18 years of age with anemia of chronic kidney disease (CKD) at screening Estimated glomerular filtration rate of < 60 mL/min/1.73 m2 (Modification of Diet in Renal Disease [MDRD] or the formula according to Matsuo, et al) Not on dialysis and not expected to begin dialysis during the treatment period of the study (at least 16 weeks from randomization) Not treated with any erythropoiesis-stimulating agent (ESA) within 8 weeks before randomization Mean screening Hb concentration </= 10.5 g/dL Body weight of 45 kg to 125 kg, inclusive, at screening Exclusion Criteria: Subjects with significant acute or chronic bleeding, such as overt gastrointestinal bleeding Chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission Previous or concurrent cancer except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, and T1) or any cancer curatively treated > 3 years prior to randomization Subjects treated with any ESA within the 8 weeks before randomization Red blood cell (RBC) containing transfusion within the 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 initial screening visit Severe rhythm or conduction disorders (e.g., HR < 50 or > 110 bpm, atrial flutter, prolonged QT > 500 msec, third degree atrioventricular [AV] block) New York Heart Association Class III or IV congestive heart failure Severe hepatic insufficiency (defined as alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 x the upper limit of normal [ULN], total bilirubin > 2 mg/dL, or Child-Pugh B and C) or active hepatitis, in the investigator's opinion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY85-3934 (25mg OD)<br>25 mg once daily (OD) of BAY85-3934 Morning: 1 tablet BAY85-3934 25 mg and 2 tablets matching placebo Evening: 3 tablets matching placebo | Drug: BAY85-3934<br>* 25mg Tablet<br>Drug: Placebo<br>* Matching placebo tablet<br>|
| Experimental: BAY85-3934 (50mg OD)<br>50 mg OD of BAY85-3934 Morning: 2 tablets BAY85-3934 25 mg and 1 tablet matching placebo Evening: 3 tablets matching placebo | Drug: BAY85-3934<br>* 25mg Tablet<br>Drug: Placebo<br>* Matching placebo tablet<br>|
| Experimental: BAY85-3934 (75mg OD)<br>75 mg OD of BAY85-3934 Morning: 3 tablets BAY85-3934 25 mg Evening: 3 tablets matching placebo | Drug: BAY85-3934<br>* 25mg Tablet<br>Drug: Placebo<br>* Matching placebo tablet<br>|
| Experimental: BAY85-3934 (25mg BID)<br>25 mg twice daily (BID) of BAY85-3934 Morning and evening: 1 tablet BAY85-3934 25 mg and 2 tablets matching placebo | Drug: BAY85-3934<br>* 25mg Tablet<br>Drug: Placebo<br>* Matching placebo tablet<br>|
| Experimental: BAY85-3934 (50mg BID)<br>50 mg BID of BAY85-3934 Morning and evening: 2 tablets BAY85-3934 25 mg and 1 tablet matching placebo | Drug: BAY85-3934<br>* 25mg Tablet<br>Drug: Placebo<br>* Matching placebo tablet<br>|
| Placebo Comparator: Placebo BID<br>Placebo BID Morning and evening: 3 tablets of placebo matching BAY85-3934 25 mg | Drug: Placebo<br>* Matching placebo tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in local laboratory hemoglobin level from baseline to the average during the last 4 weeks treatment period |  | Baseline and week 12 to 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in local laboratory hemoglobin level from baseline |  | Baseline up to 12 weeks | 
| Speed of change in hemoglobin level per unit time |  | Up to 16 weeks | 
| Duration of treatment exposure |  | Up to 16 weeks | 
| Number of participants with serious adverse events as a measure of safety and tolerability |  | Up to 16 weeks | 
| Pharmacodynamics characterized by erythropoietin concentration |  | Several time points up to 16 weeks | 
| Pharmacodynamics characterized by reticulocyte count |  | Several time points up to 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anemia of CKD