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A Study of Intravenous (iv) Mircera in Hemodialysis Patients With Chronic Renal Anemia

Phase 2
Completed
Conditions
Anemia
Interventions
Drug: methoxy polyethylene glycol-epoetin beta [Mircera]
Registration Number
NCT00048035
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This study will determine the appropriate dose and frequency of administration of iv Mircera maintenance therapy in hemodialysis patients with chronic renal anemia who were previously receiving iv epoetin. The anticipated time on study treatment is 3-12 months and the target sample size is \<100 individuals.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
91
Inclusion Criteria
  • adult patients >=18 years of age;
  • chronic renal anemia;
  • on hemodialysis therapy for at least 3 months;
  • receiving iv epoetin alfa during the 2 weeks prior to the run-in period.
Exclusion Criteria
  • women who are pregnant, breastfeeding or using unreliable birth control methods;
  • use of any investigational drug within 30 days of the run-in phase, or during the run-in or study treatment period.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 6 (RO0503821 [0.6/150 1x/2week])methoxy polyethylene glycol-epoetin beta [Mircera]Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).
Cohort 2 (RO0503821 [0.25/150 1x/2week])methoxy polyethylene glycol-epoetin beta [Mircera]Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to 62.50% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).
Cohort 4 (RO0503821 [0.4/150 1x/2week])methoxy polyethylene glycol-epoetin beta [Mircera]Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).
Cohort 5 (RO0503821 [0.6/150 1x/week])methoxy polyethylene glycol-epoetin beta [Mircera]Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).
Cohort 1 (RO0503821 [0.25/150 1x/week])methoxy polyethylene glycol-epoetin beta [Mircera]Eligible participant will be administered RO0503821 (methoxy polyethylene glycol-epoetin beta \[Mircera\]) intravenously (IV) using a dose conversion factor of 0.25/150 microgram (mcg)/kilogram (kg) of the previous weekly erythropoiesis stimulating agents (ESA) dose, (equal to 62.50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).
Cohort 3 (RO0503821 [0.4/150 1x/week])methoxy polyethylene glycol-epoetin beta [Mircera]Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each).
Primary Outcome Measures
NameTimeMethod
Median Change From Baseline in Hemoglobin Levels to End of Initial Treatment Under Constant Dosing RegimenFrom Baseline (Day -28 to Day 1) to EOIT (Week 19)

Median change from Baseline in hemoglobin (Hb) levels to end of initial treatment (EOIT) under constant dosing regimen was reported. For ease of interpretation, all individual slope values were multiplied by 42 to give an estimate of change in Hb values over six weeks. Baseline (Day -28 to Day 1) Hb values was calculated as the mean of the screening assessment (SA) and run-in period (Week -2 and Week -1). For all participants, an EOIT value was calculated as the last observed Hb value before a dose change or blood transfusion. For participants without any dose adjustments or blood transfusion, the EOIT value was identical to the Week 19 value.

Secondary Outcome Measures
NameTimeMethod
Median Change From Baseline in Hematocrit Levels to End of Initial Treatment Under Constant Dosing RegimenFrom Baseline (Day -28 to Day 1) to EOIT (Week 19)

Median change from Baseline in hematocrit (Hct) levels to end of initial treatment under constant dosing regimen was reported. Baseline (Day -28 to Day 1) Hct values was calculated as the mean of the SA and run-in period (Weeks -2 and -1). For all participants, an EOIT value was calculated as the last observed Hct value before a dose change or blood transfusion. For participants without any dose adjustments or blood transfusion, the EOIT value was identical to the Week 19 value.

Number of Participants With Any Adverse Events, Any Serious Adverse Events, And DeathsUp to Week 126

An Adverse Events (AEs) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious Adverse Events (SAEs) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes. ). The study design tested 3 different starting dose conversion factors at 3 different dosing schedules during the core study period. As study drug doses can be modified continually over time all results for the two long term safety periods were displayed by dose schedule group only.

Number of Participants With Marked Laboratory AbnormalitiesUp to Week 126

Marked abnormality was defined as above and/or below a value which was considered to be potentially clinically relevant. The number of participants with marked lab abnormality across treatment groups were reported and presented. Marked laboratory abnormalities were analyzed according to the Roche specified limits for the following reference range: White blood cells (WBC) (3.0- 18.0 10\^9/L), Platelets (100 - 550 10\^9/L), Alanine aminotransferase (ALAT) \[0 110 units per litre (U/L)\], Alkaline Phosphatase (ALP) (0 - 220 U/L), Aspartate aminotransferase (ASAT) (0 - 80 U/L), Albumin \>= 30 g/L, Phosphate \[0.75 - 1.60 millimoles per liter (mmol/L)\], Potassium (2.9 - 5.8 mmol/L), Glucose (2.80 - 11.10 mmol/L).

Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Before and After DialysisFrom Baseline (Day -28 to Day 1) to Week 126

Mean Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) is calculated as the end of treatment values minus the Baseline value. Baseline (Day -28 to Day 1) values were calculated as the mean of the screening assessment (SA) and run-in period (Week -2 and Week -1).

Mean Change in Pulse RateUp to Week 126

Participants pulse rates in beats per minute (BpM) were analyzed at sitting position using descriptive statistical methods (ie, means, standard deviations and percentiles). The changes in pulse rate throughout the study were analysed at each study visit and mean change is reported.

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