Clinical Study of R744 to Predialysis Patients( Phase III, Comparative Study in Comparison With Epoetin Beta)

Study Overview
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Brief Summary
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This study used as the comparative drug (epoetin beta) will assess the efficacy and safety of subcutaneous R744 in renal anemia patients on Predialysis.

Official Title
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Correction and Maintenance Study of Subcutaneous Injections of R744 to Predialysis Patients ( Phase III, Comparative Study in Comparison With Epoetin Beta)

Conditions
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Predialysis Patients

Intervention / Treatment
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* Drug: R744
* Drug: Epoetin beta


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients whose serum creatinine level has been ≥ 2.0 mg/dL or creatinine clearance has been ≤ 30 mL /min at any one time point within 12 weeks before registration Patients aged ≥ 20 years at the time of obtaining consent Patients who have been not receiving a rHuEPO preparation at least 16 weeks before registration Patients whose value of Hb concentrations determined the nearest week before registration has been < 10.0 g/dL Patients whose transferrin saturation has been ≥ 20 % or ferritin has been ≥ 100ng/mL at any time point within 8 weeks before registration Exclusion Criteria: Patients with hardly controllable hypertension (patients whose diastolic blood pressure has been ≥ 100 mmHg on more than 1/3 of the determining occasions within 12 weeks before registration) Patients with congestive cardiac failure (≥ Class III in NYHA cardiac function classification) Female patients who are pregnant, lactating, possibly pregnant or not willing to take a contraceptive measure in the period from the day of starting the treatment with the study drug to 90 days after the day of the last dose of the study drug Patients with complication of myocardial infarction, pulmonary infarction or cerebral infarction (excluding asymptomatic cerebral infarction) Patients confirmed to have serious allergy or serious drug allergy (shock, anaphylactoid symptom) Patients hypersensitive to a rHuEPO preparation Patients with malignant tumor (including hemic malignant tumor), severe infection, systemic hemic disease (osteomyelodysplasia syndrome, hemoglobinopathy, etc.), hemolytic anemia or apparent hemorrhagic lesion such as digestive tract hemorrhage Patients who have received an anabolic hormone preparation, testosterone enanthate or mepitiostane within 12 weeks before registration Patients who have received another investigational drug within 12 weeks before registration Patients who have received R744 before registration Patients whose AST(GOT) value ≥ 100 IU/L or ALT(GPT) value ≥ 100 IU/L before registration Patients who have received erythrocyte transfusion within 16 weeks before registration Patients for whom a surgical operation accompanied by marked bleeding is planned during the study period In addition, patients who are judged as ineligible to participate in this study by the investigator or subinvestigator

Ages Eligible for Study
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Minimum Age: 20 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2<br> | Drug: Epoetin beta<br>* 6000IU(s.c.)/week until Hb concentration reaches to 10.0g/dL or above and the increasing amount of Hb concentration reaches to 1.0g/dL or above,then 3000k 12000IU(s.c.)/2week for 24 26weeks in total.<br>|
| Experimental: 1<br> | Drug: R744<br>* 25μg(s.c.)/2weeks until Hb concentration reaches to 10g/dL or above and the increasing amount of Hb concentration reaches to 1.0g/dL or above, then 25 250μg(s.c.)/4week for 24 26weeks in total.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients who maintain mean Hb concentration in the range of ≥ 10.0g/dL and ≤ 12.0g/dL |  | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Hb concentration for term of evaluation |  | 26 weeks | 
| The ratio of patients whose Hb concentration reach ≥ 10.0g/dL and increasing amount of Hb concentration reach ≥ 1.0g/dL |  | 26 weeks | 
| Time required for reaching Hb concentration of ≥ 10.0 g/dL and reaching increasing amount of Hb concentration of ≥ 1.0g/dL |  | 26 weeks | 
| Slope of regression line of Hb concentration per week |  | 26 weeks | 
| Variation of QOL |  | 26 weeks | 
| Adverse events |  | 26 weeks | 
| Laboratory measurements |  | 26 weeks | 
| Vital signs, standard 12-lead ECG |  | 26 weeks | 
| Anti-R744 antibody titer |  | 26 weeks | 
| Anti-Epoetin beta antibody titer |  | 26 weeks |