Anemia
Conditions
Brief summary
This study will assess the efficacy and safety of intravenous Mircera, given as maintenance treatment for renal anemia in chronic kidney disease patients on dialysis who were previously receiving iv epoetin. The anticipated time on study treatment is 1-2 years and the target sample size is 100-500 individuals.
Interventions
intravenously 3 times weekly for 52 weeks, as prescribed
DRUGRO0503821 (1x/2 Weeks)
60, 100, or 180 microgram (mcg) (starting dose) once every two weeks intravenously for 52 weeks.
DRUGRO0503821 (1x/4 Weeks)
120, 200 or 360 mcg (starting dose) once every four weeks intravenously for 52 weeks.
Sponsors
Hoffmann-La Roche
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
* adult patients \>=18 years of age; * chronic renal anemia; * on dialysis therapy for at least 12 weeks before screening; * receiving IV epoetin for at least 8 weeks before screening.
Exclusion criteria
* women who are pregnant, breastfeeding or using unreliable birth control methods; * administration of another investigational drug within 4 weeks before screening, or during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Hemoglobin (Hb) Concentration From Baseline to Evaluation Period | Baseline, Week 29 to Week 36 | A time adjusted mean change in Hb concentration was calculated using an Area Under the Curve (AUC) approach, for both periods separately. Change in Hb concentration between the Baseline and evaluation periods was calculated by subtracting the calculated average baseline Hb from the average evaluation period Hb. At the end of the Week 36, data allowing the evaluation of the therapeutic response was available for 188 out of 221 eligible participants in RO0503821 (1x/2 Weeks) arm; 172 out of 220 eligible participants in RO0503821 (1x/4 Weeks); and 180 out of 225 participants in Epoetin (1-3x/Weeks) arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods | Week 1 to Week 36 | The number of participants who received RBC transfusions during the titration and evaluation periods were reported . |
| Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | Up to Week 53 | Marked laboratory abnormalities were defined as those values that were outside the Roche marked abnormality reference range. These abnormality laboratory values were flagged as Low or High if they were below the lower limit or above the upper limit of Roche marked abnormality reference range, respectively. The marked abnormality reference range for Platelet was 100-550x10\^9/Litre \[L\], for WBC was 3.0-18.0.0x10\^9/L, and for RBC was 3.80-6.10x10\^12/L. |
| Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Up to Week 53 | Marked laboratory abnormalities were defined as those values that were outside the Roche marked abnormality reference range. These abnormality laboratory values were flagged as Low or High if they were below the lower limit or above the upper limit of Roche marked abnormality reference range, respectively. The marked abnormality reference range for aspartate aminotransferase (AST) was 0-80 (unit per litre \[U/L\]), alanine aminotransferase (ALT) 0-110 U/L, alkaline phosphatase (ALP) 0-220 U/L, albumin \>=30.0 gram/litre (g/L), glucose in non-diabetics 2.80-11.10 (millimol/litre \[mmol/L\]); potassium 2.90-5.80 mmol/L, and phosphorus 0.75-1.60 mmol/L |
| Number of Participants Maintaining Average Hemoglobin Concentration During Evaluation Period Within +/- 1 Gram Per Deciliter (g/dl) of Average Baseline Hemoglobin Concentration. | Baseline, Week 29 to Week 36 | The mean Hb of all values recorded during the evaluation period were calculated, and were subtracted from the mean baseline Hb for each participant. The number of participants maintaining their average Hb within +/- 1 g/dL of their average baseline hemoglobin concentration is given. |
| Mean Change in Pulse Rate (Sitting) From Baseline at Week 36 and Week 52 | Baseline, Week 36 and Week 52 | Change in pulse rate (beats per minute \[bpm\]) from baseline values includes only those participants with both a baseline value and a value for specified time period. |
| Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Upto Week 53 | An AE 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. An SAE 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. Overall deaths occurred in the study were reported. |
| Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Baseline, Week 36 and Week 52 | Blood pressure was measured by manual assessment or automated reading throughout the entire study for every participant. Blood pressure was taken in the sitting position after at least 5 minutes rest. An appropriate -sized cuff was used and both systolic (SBP) and diastolic (DBP) blood pressures were recorded before dialysis (BD) and after dialysis (AD). |
Countries
Canada, France, Germany, Italy, Norway, Spain, Switzerland, United States
Participant flow
Recruitment details
A total of 673 participants were recruited at 91 centers in 8 countries with chronic renal anemia and dialysis therapy for at least 12 weeks before screening and during the screening/baseline period. This study was conducted between February 25, 2004 and August 17, 2005
Participants by arm
| Arm | Count |
|---|---|
| RO0503821 (1x/2 Weeks) Participants received RO0503821 once every two weeks intravenously for 52 weeks. Participants received a starting dose of RO0503821 (60, 100, or 180 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug. | 221 |
| RO0503821 (1x/4 Weeks) Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants received a starting dose of RO0503821 (120, 200, or 360 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug. | 220 |
| Epoetin (1-3x/Weeks) Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks. | 225 |
| Total | 666 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 7 | 1 |
| Overall Study | Change in dialysis modality | 1 | 0 | 0 |
| Overall Study | Death | 17 | 13 | 13 |
| Overall Study | Financial issues | 0 | 1 | 0 |
| Overall Study | Given Epogen in hospital | 1 | 0 | 0 |
| Overall Study | Insufficient Therapeutic Response | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 2 |
| Overall Study | Multiple blood transfusions | 0 | 0 | 1 |
| Overall Study | Principal Investigator's decision | 1 | 0 | 1 |
| Overall Study | Relocation | 0 | 8 | 5 |
| Overall Study | Renal transplant | 12 | 15 | 11 |
| Overall Study | Sponsors decision to withdraw | 0 | 0 | 1 |
| Overall Study | Transferred to nursing home | 0 | 0 | 1 |
| Overall Study | Transferred to other unit | 0 | 0 | 1 |
| Overall Study | Transfer to other center for surgery | 1 | 0 | 0 |
| Overall Study | Transfer to satellite unit | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 10 | 6 |
| Overall Study | Withdrew from dialysis care | 5 | 0 | 3 |
| Overall Study | Worsening of health condition | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | RO0503821 (1x/2 Weeks) | RO0503821 (1x/4 Weeks) | Epoetin (1-3x/Weeks) | Total |
|---|---|---|---|---|
| Age, Continuous | 59.2 years STANDARD_DEVIATION 15.05 | 59.0 years STANDARD_DEVIATION 15 | 58.5 years STANDARD_DEVIATION 15.16 | 58.9 years STANDARD_DEVIATION 15.05 |
| Gender Female | 89 Participants | 95 Participants | 92 Participants | 276 Participants |
| Gender Male | 132 Participants | 125 Participants | 133 Participants | 390 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 166 / 221 | 151 / 220 | 175 / 225 |
| serious Total, serious adverse events | 101 / 221 | 87 / 220 | 99 / 225 |
Outcome results
Primary
Mean Change in Hemoglobin (Hb) Concentration From Baseline to Evaluation Period
A time adjusted mean change in Hb concentration was calculated using an Area Under the Curve (AUC) approach, for both periods separately. Change in Hb concentration between the Baseline and evaluation periods was calculated by subtracting the calculated average baseline Hb from the average evaluation period Hb. At the end of the Week 36, data allowing the evaluation of the therapeutic response was available for 188 out of 221 eligible participants in RO0503821 (1x/2 Weeks) arm; 172 out of 220 eligible participants in RO0503821 (1x/4 Weeks); and 180 out of 225 participants in Epoetin (1-3x/Weeks) arm.
Time frame: Baseline, Week 29 to Week 36
Population: The Per Protocol population included all randomized participants except those not meeting inclusion criterion related to Hb parameters and \<5 recorded Hb values during the evaluation period with missing administrations of the study drug/ reference drug. Please refer to the outcome measure description section for more details.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RO0503821 (1x/2 Weeks) | Mean Change in Hemoglobin (Hb) Concentration From Baseline to Evaluation Period | -0.10 gram per deciliter (g/dL) | Standard Deviation 1.06 |
| RO0503821 (1x/4 Weeks) | Mean Change in Hemoglobin (Hb) Concentration From Baseline to Evaluation Period | 0.01 gram per deciliter (g/dL) | Standard Deviation 0.96 |
| Epoetin (1-3x/Week) | Mean Change in Hemoglobin (Hb) Concentration From Baseline to Evaluation Period | -0.10 gram per deciliter (g/dL) | Standard Deviation 0.92 |
Comparison: The non-inferiority test for treatment differences in Hb change from baseline, based on analysis of co-variance (ANCOVA) analysis with a non-inferiority limit of -0.75 g/dL.p-value: <0.000197.5% CI: [-0.215, 0.223]ANCOVA, CI for difference between groups
Comparison: The non-inferiority test for treatment differences in Hb change from baseline, based on ANCOVA analysis with a non-inferiority limit of -0.75 g/dL.p-value: <0.000197.5% CI: [-0.173, 0.275]ANCOVA, CI for difference between groups
Secondary
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death
An AE 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. An SAE 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. Overall deaths occurred in the study were reported.
Time frame: Upto Week 53
Population: The Safety Population was defined as all participants who received at least one dose of RO0503821 or Epoetin, and a safety follow-up, whether withdrawn prematurely or not. Participants available at particular time point were included in the analysis (n).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RO0503821 (1x/2 Weeks) | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Number of participants with serious adverse events | 101 participants |
| RO0503821 (1x/2 Weeks) | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Number of participants with adverse events | 203 participants |
| RO0503821 (1x/2 Weeks) | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Number of deaths | 19 participants |
| RO0503821 (1x/4 Weeks) | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Number of participants with serious adverse events | 87 participants |
| RO0503821 (1x/4 Weeks) | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Number of participants with adverse events | 202 participants |
| RO0503821 (1x/4 Weeks) | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Number of deaths | 15 participants |
| Epoetin (1-3x/Week) | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Number of participants with adverse events | 214 participants |
| Epoetin (1-3x/Week) | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Number of deaths | 17 participants |
| Epoetin (1-3x/Week) | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | Number of participants with serious adverse events | 99 participants |
Secondary
Mean Change in Blood Pressure From Baseline at Week 36 and Week 52
Blood pressure was measured by manual assessment or automated reading throughout the entire study for every participant. Blood pressure was taken in the sitting position after at least 5 minutes rest. An appropriate -sized cuff was used and both systolic (SBP) and diastolic (DBP) blood pressures were recorded before dialysis (BD) and after dialysis (AD).
Time frame: Baseline, Week 36 and Week 52
Population: The Safety Population was defined as all participants who received at least one dose of RO0503821 or Epoetin, and a safety follow-up, whether withdrawn prematurely or not. Participants available at particular time point were included in the analysis (n).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO0503821 (1x/2 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in DBP, AD at Wk 52 (n=167, 168, 178) | -1 millimeter of mercury (mmHg) | Standard Deviation 14.9 |
| RO0503821 (1x/2 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in SBP, BD at Wk 36 (n=189, 178,196) | 1 millimeter of mercury (mmHg) | Standard Deviation 25.3 |
| RO0503821 (1x/2 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in DBP, BD at Wk 52 (n=168, 166, 179) | 1 millimeter of mercury (mmHg) | Standard Deviation 15.2 |
| RO0503821 (1x/2 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in DBP, AD at Wk 36 (n=189, 177, 196) | -1 millimeter of mercury (mmHg) | Standard Deviation 16.4 |
| RO0503821 (1x/2 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in SBP, BD at Wk 52 (n=168, 166, 180) | -0 millimeter of mercury (mmHg) | Standard Deviation 24.6 |
| RO0503821 (1x/2 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in SBP, AD at Wk 36 (n=189, 177, 196) | 3 millimeter of mercury (mmHg) | Standard Deviation 28.3 |
| RO0503821 (1x/2 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in DBP, BD at Wk 36 (n=189, 178, 195) | 0 millimeter of mercury (mmHg) | Standard Deviation 14.7 |
| RO0503821 (1x/2 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in SBP, AD at Wk 52 (n=167, 168, 179) | 2 millimeter of mercury (mmHg) | Standard Deviation 24.5 |
| RO0503821 (1x/4 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in DBP, BD at Wk 36 (n=189, 178, 195) | -3 millimeter of mercury (mmHg) | Standard Deviation 16.3 |
| RO0503821 (1x/4 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in SBP, BD at Wk 52 (n=168, 166, 180) | -3 millimeter of mercury (mmHg) | Standard Deviation 24.6 |
| RO0503821 (1x/4 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in DBP, AD at Wk 36 (n=189, 177, 196) | -0 millimeter of mercury (mmHg) | Standard Deviation 15.2 |
| RO0503821 (1x/4 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in SBP, BD at Wk 36 (n=189, 178,196) | -2 millimeter of mercury (mmHg) | Standard Deviation 22.7 |
| RO0503821 (1x/4 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in DBP, AD at Wk 52 (n=167, 168, 178) | -0 millimeter of mercury (mmHg) | Standard Deviation 15.9 |
| RO0503821 (1x/4 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in SBP, AD at Wk 52 (n=167, 168, 179) | -0 millimeter of mercury (mmHg) | Standard Deviation 29.3 |
| RO0503821 (1x/4 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in DBP, BD at Wk 52 (n=168, 166, 179) | -3 millimeter of mercury (mmHg) | Standard Deviation 18.3 |
| RO0503821 (1x/4 Weeks) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in SBP, AD at Wk 36 (n=189, 177, 196) | -1 millimeter of mercury (mmHg) | Standard Deviation 27 |
| Epoetin (1-3x/Week) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in DBP, AD at Wk 52 (n=167, 168, 178) | -3 millimeter of mercury (mmHg) | Standard Deviation 14.9 |
| Epoetin (1-3x/Week) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in SBP, BD at Wk 36 (n=189, 178,196) | 3 millimeter of mercury (mmHg) | Standard Deviation 25.1 |
| Epoetin (1-3x/Week) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in SBP, BD at Wk 52 (n=168, 166, 180) | 1 millimeter of mercury (mmHg) | Standard Deviation 26 |
| Epoetin (1-3x/Week) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in DBP, BD at Wk 36 (n=189, 178, 195) | 1 millimeter of mercury (mmHg) | Standard Deviation 16.8 |
| Epoetin (1-3x/Week) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in DBP, BD at Wk 52 (n=168, 166, 179) | -1 millimeter of mercury (mmHg) | Standard Deviation 15.4 |
| Epoetin (1-3x/Week) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in SBP, AD at Wk 52 (n=167, 168, 179) | 1 millimeter of mercury (mmHg) | Standard Deviation 24.9 |
| Epoetin (1-3x/Week) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in DBP, AD at Wk 36 (n=189, 177, 196) | -2 millimeter of mercury (mmHg) | Standard Deviation 12.4 |
| Epoetin (1-3x/Week) | Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Change in SBP, AD at Wk 36 (n=189, 177, 196) | -0 millimeter of mercury (mmHg) | Standard Deviation 24.3 |
Secondary
Mean Change in Pulse Rate (Sitting) From Baseline at Week 36 and Week 52
Change in pulse rate (beats per minute \[bpm\]) from baseline values includes only those participants with both a baseline value and a value for specified time period.
Time frame: Baseline, Week 36 and Week 52
Population: The Safety Population was defined as all participants who received at least one dose of RO0503821 or Epoetin, and a safety follow-up, whether withdrawn prematurely or not. Participants available at particular time point were included in the analysis (n).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO0503821 (1x/2 Weeks) | Mean Change in Pulse Rate (Sitting) From Baseline at Week 36 and Week 52 | Change from BL at Week 52 (n=168, 166, 179) | 1 beats per minute (bpm) | Standard Deviation 13.6 |
| RO0503821 (1x/2 Weeks) | Mean Change in Pulse Rate (Sitting) From Baseline at Week 36 and Week 52 | Change from BL at Week 36 (n=188, 176, 193) | 1 beats per minute (bpm) | Standard Deviation 12 |
| RO0503821 (1x/4 Weeks) | Mean Change in Pulse Rate (Sitting) From Baseline at Week 36 and Week 52 | Change from BL at Week 36 (n=188, 176, 193) | 2 beats per minute (bpm) | Standard Deviation 11.8 |
| RO0503821 (1x/4 Weeks) | Mean Change in Pulse Rate (Sitting) From Baseline at Week 36 and Week 52 | Change from BL at Week 52 (n=168, 166, 179) | 1 beats per minute (bpm) | Standard Deviation 13.4 |
| Epoetin (1-3x/Week) | Mean Change in Pulse Rate (Sitting) From Baseline at Week 36 and Week 52 | Change from BL at Week 36 (n=188, 176, 193) | 0 beats per minute (bpm) | Standard Deviation 14.5 |
| Epoetin (1-3x/Week) | Mean Change in Pulse Rate (Sitting) From Baseline at Week 36 and Week 52 | Change from BL at Week 52 (n=168, 166, 179) | -1 beats per minute (bpm) | Standard Deviation 13.2 |
Secondary
Number of Participants Maintaining Average Hemoglobin Concentration During Evaluation Period Within +/- 1 Gram Per Deciliter (g/dl) of Average Baseline Hemoglobin Concentration.
The mean Hb of all values recorded during the evaluation period were calculated, and were subtracted from the mean baseline Hb for each participant. The number of participants maintaining their average Hb within +/- 1 g/dL of their average baseline hemoglobin concentration is given.
Time frame: Baseline, Week 29 to Week 36
Population: The intent-to-treat (ITT) population was defined as all randomized participants. At the end of Week 36, data allowing the evaluation of the therapeutic response was available for 196/221, 188/220, and 205/225 participants in RO0503821 (1x/2 Weeks), RO0503821 (1x/4 Weeks), and Epoetin (1 -3x/Weeks), respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RO0503821 (1x/2 Weeks) | Number of Participants Maintaining Average Hemoglobin Concentration During Evaluation Period Within +/- 1 Gram Per Deciliter (g/dl) of Average Baseline Hemoglobin Concentration. | 133 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants Maintaining Average Hemoglobin Concentration During Evaluation Period Within +/- 1 Gram Per Deciliter (g/dl) of Average Baseline Hemoglobin Concentration. | 127 participants |
| Epoetin (1-3x/Week) | Number of Participants Maintaining Average Hemoglobin Concentration During Evaluation Period Within +/- 1 Gram Per Deciliter (g/dl) of Average Baseline Hemoglobin Concentration. | 138 participants |
Secondary
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes
Marked laboratory abnormalities were defined as those values that were outside the Roche marked abnormality reference range. These abnormality laboratory values were flagged as Low or High if they were below the lower limit or above the upper limit of Roche marked abnormality reference range, respectively. The marked abnormality reference range for aspartate aminotransferase (AST) was 0-80 (unit per litre \[U/L\]), alanine aminotransferase (ALT) 0-110 U/L, alkaline phosphatase (ALP) 0-220 U/L, albumin \>=30.0 gram/litre (g/L), glucose in non-diabetics 2.80-11.10 (millimol/litre \[mmol/L\]); potassium 2.90-5.80 mmol/L, and phosphorus 0.75-1.60 mmol/L
Time frame: Up to Week 53
Population: The Safety Population was defined as all participants who received at least one dose of RO0503821 or Epoetin, and a safety follow-up, whether withdrawn prematurely or not. Participants available at particular time point were included in the analysis (n).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High ALT. (n=218, 216, 224) | 4 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High ALP (n=218, 216, 224) | 15 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Low Albumin (n=218, 216, 224) | 14 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High Phosphate (n=218, 216, 224) | 106 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Low Phosphate (n=218, 216, 224) | 21 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High Potassium (n=218, 216, 224) | 33 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Low Potassium (n=218, 216, 224) | 10 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High AST (n=218, 215, 224) | 6 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High Blood glucose in non-diabetic (n=114,131,110) | 0 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Low Blood Glucose in Non-Diabetic (n=114,131,110) | 0 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High Blood glucose in non-diabetic (n=114,131,110) | 3 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High ALT. (n=218, 216, 224) | 2 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High Potassium (n=218, 216, 224) | 35 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Low Phosphate (n=218, 216, 224) | 21 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High ALP (n=218, 216, 224) | 14 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Low Blood Glucose in Non-Diabetic (n=114,131,110) | 1 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High AST (n=218, 215, 224) | 3 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Low Albumin (n=218, 216, 224) | 13 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Low Potassium (n=218, 216, 224) | 3 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High Phosphate (n=218, 216, 224) | 95 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High AST (n=218, 215, 224) | 4 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High Phosphate (n=218, 216, 224) | 94 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Low Phosphate (n=218, 216, 224) | 17 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High Potassium (n=218, 216, 224) | 36 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High Blood glucose in non-diabetic (n=114,131,110) | 1 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Low Potassium (n=218, 216, 224) | 3 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High ALT. (n=218, 216, 224) | 5 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Low Blood Glucose in Non-Diabetic (n=114,131,110) | 0 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | High ALP (n=218, 216, 224) | 16 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Low Albumin (n=218, 216, 224) | 18 participants |
Secondary
Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC)
Marked laboratory abnormalities were defined as those values that were outside the Roche marked abnormality reference range. These abnormality laboratory values were flagged as Low or High if they were below the lower limit or above the upper limit of Roche marked abnormality reference range, respectively. The marked abnormality reference range for Platelet was 100-550x10\^9/Litre \[L\], for WBC was 3.0-18.0.0x10\^9/L, and for RBC was 3.80-6.10x10\^12/L.
Time frame: Up to Week 53
Population: The Safety Population was defined as all participants who received at least one dose of RO0503821 or Epoetin, and a safety follow-up, whether withdrawn prematurely or not. Participants available at particular time point were included in the analysis (n).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | High Platelet (n=218, 216, 223) | 0 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | Low Platelet (n=218, 216, 223) | 14 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | High WBC (n=218, 217, 223) | 0 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | Low WBC (n=218, 217, 223) | 8 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | High RBC (n=124, 129, 89) | 1 participants |
| RO0503821 (1x/2 Weeks) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | Low RBC (n=124, 129, 89) | 1 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | Low RBC (n=124, 129, 89) | 2 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | High Platelet (n=218, 216, 223) | 1 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | Low WBC (n=218, 217, 223) | 6 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | High RBC (n=124, 129, 89) | 2 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | Low Platelet (n=218, 216, 223) | 10 participants |
| RO0503821 (1x/4 Weeks) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | High WBC (n=218, 217, 223) | 2 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | Low Platelet (n=218, 216, 223) | 6 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | High WBC (n=218, 217, 223) | 3 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | Low RBC (n=124, 129, 89) | 0 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | Low WBC (n=218, 217, 223) | 5 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | High Platelet (n=218, 216, 223) | 3 participants |
| Epoetin (1-3x/Week) | Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | High RBC (n=124, 129, 89) | 0 participants |
Secondary
The Incidence of Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods
The number of participants who received RBC transfusions during the titration and evaluation periods were reported .
Time frame: Week 1 to Week 36
Population: The Safety Population was defined as all participants who received at least one dose of RO0503821 or Epoetin, and a safety follow-up, whether withdrawn prematurely or not.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RO0503821 (1x/2 Weeks) | The Incidence of Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods | 21 participants |
| RO0503821 (1x/4 Weeks) | The Incidence of Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods | 16 participants |
| Epoetin (1-3x/Week) | The Incidence of Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods | 17 participants |