Clinical Study of R744 to Hemodialysis Patients

Switch and Maintenance Study of Intravenous Injections of R744 to Hemodialysis Patients ( Phase III, Double Blind Study in Comparison With Epoetin Beta).

This study used as the comparative drug (epoetin beta) will assess the efficacy and safety of intravenous injections of R744 in renal anemia patients on Hemodialysis patients.

Study Overview

• Status: Completed
• Conditions: Hemodialysis Patients
• Intervention / Treatment: Drug: R744; Drug: R744; Drug: rHuEPO placebo; Drug: rHuEPO; Drug: rHuEPO; Drug: R744 placebo

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chubu, Japan
    • Chubu Region
  • Chugoku/Shikoku, Japan
    • Chugoku/Shikoku region
  • Kanto/Koshinetsu, Japan
    • Kanto/Koshinetsu region
  • Kinki/Hokuriku, Japan
    • Kinki/Hokuriku region
  • Kyusyu, Japan
    • Kyusyu region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who have been receiving hemodialysis 3 times a week for at least 12 weeks before registration
• Patients aged ≥ 20 years at the time of obtaining consent
• Patients who have been receiving a rHuEPO preparation at least once a week for at least 8 weeks before registration
• Within 4 weeks before registration, patients who have been receiving a rHuEPO preparation 750IU (3 times a week), 1,500IU (twice a week (1st and 2nd hemodialysis day of the week, or1st and 3rd hemodialysis day of the week)), 1,500IU (3 times a week), or 3,000IU (twice a week (1st and 2nd hemodialysis day of the week, or1st and 3rd hemodialysis day of the week)), and patients who have not change dosage and administration.
• Patients whose pre-dialysis Hb concentrations has been between ≥ 9.0 g/dL and ≤12.0 g/dL and mean value of pre-dialysis Hb concentrations has been between ≥ 9.5 g/dL and ≤11.5 g/dL determined at the beginning of each week within 8 weeks before registration
• 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, testosterone propionate, methyltestosterone 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: R744; 100μg/4week for 8 weeks, then 50~250μg/4week for 16 weeks; Other Names: methoxy polyethylene glycol-epoetin beta; Drug: R744; 150μg/4week for 8 weeks, then 50~250μg/4week for 16 weeks; Other Names: methoxy polyethylene glycol-epoetin beta; Drug: rHuEPO placebo; 0 IU 2 or 3 times/week for 8 weeks, then 1~3 times/week for 16 weeks
Experimental: 2	Drug: R744; 100μg/4week for 8 weeks, then 50~250μg/4week for 16 weeks; Other Names: methoxy polyethylene glycol-epoetin beta; Drug: R744; 150μg/4week for 8 weeks, then 50~250μg/4week for 16 weeks; Other Names: methoxy polyethylene glycol-epoetin beta; Drug: rHuEPO placebo; 0 IU 2 or 3 times/week for 8 weeks, then 1~3 times/week for 16 weeks
Active Comparator: 3	Drug: rHuEPO; 2250IU or 3000IU(i.v.) 2 or 3 times/week for 8 weeks, then 750~9000IU(i.v.)/1~3week for 16 weeks; Drug: rHuEPO; 4500IU or 6000IU(i.v.) 2 or 3times/week for 8 weeks, then 750~9000IU(i.v.)/1~3week for 16 weeks; Drug: R744 placebo; 0 μg/4week for 24 weeks
Active Comparator: 4	Drug: rHuEPO; 2250IU or 3000IU(i.v.) 2 or 3 times/week for 8 weeks, then 750~9000IU(i.v.)/1~3week for 16 weeks; Drug: rHuEPO; 4500IU or 6000IU(i.v.) 2 or 3times/week for 8 weeks, then 750~9000IU(i.v.)/1~3week for 16 weeks; Drug: R744 placebo; 0 μg/4week for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Variation of Hb concentration from baseline Hb concentration in evaluation period	week 17~24

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events	throughout study
Rate of patients who maintain Hb concentration in the range of baseline ± 1.0g/dL and maintain Hb concentration in the range of ≥ 9.0g/dL and ≤ 12.0g/dL in evaluation period	week 17~24
Rate of patients who maintain Hb concentration within ±1.0g/dL of reference Hb	week 17~24
Laboratory measurements	throughout study
Vital signs, standard 12-lead ECG	throughout study
Anti-R744 antibody titer	throughout study
Anti-Epoetin beta antibody titer	throughout study

Collaborators and Investigators

• Sponsor: Chugai Pharmaceutical
• Investigators: Study Chair: Takanori Baba, Chugai Pharmaceutical,Clinical Research Department 2

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: June 25, 2007
• First Submitted That Met QC Criteria: June 25, 2007
• First Posted (Estimate): June 26, 2007

Study Record Updates

• Last Update Posted (Estimate): February 2, 2009
• Last Update Submitted That Met QC Criteria: January 29, 2009
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematinics; Epoetin Alfa
• Other Study ID Numbers: JH20876