Anemia
Conditions
Brief summary
This single arm study will assess the efficacy, safety and tolerability of once monthly administration of subcutaneous Mircera for the maintenance of hemoglobin levels in dialysis patients with chronic renal anemia. Patients will receive subcutaneous Mircera at a starting dose of 120, 200 or 360 micrograms every 4 weeks, calculated from the last weekly dose of epoetin or darbepoetin alfa previously administered. Subsequent doses will be adjusted to maintain hemoglobin levels within the target range. Treatment duration is 56 weeks, and the target sample size is 200 individuals.
Interventions
DRUGmethoxy polyethylene glycol-epoetin beta [Mircera]
Subcutaneous injection every 4 weeks (starting dose of 120, 200 or 360 micrograms, based on previous ESA therapy)
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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; * regular long-term hemodialysis or peritoneal dialysis, with same mode of dialysis for \>=3 months; * continuous iv maintenance epoetin alfa therapy with same dosing interval during previous 2 months.
Exclusion criteria
* transfusion of red blood cells during previous 2 months; * poorly controlled hypertension; * significant acute or chronic bleeding; * active malignant disease (except non-melanoma skin cancer).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Maintaining Mean Hemoglobin Concentration Within +/- 1 g/dL of Their Reference Hb and Between 10.5 and 12.5 g/dL During Efficacy Evaluation Period | EEP (Week 17 to Week 24) | The percentage of participants who maintained their mean Hb concentration within +/- 1 g/dL of their reference Hb and between 10.5 and 12.5 g/dL during the Efficacy Evaluation Period (EEP) is reported. The EEP was from Week 17 to Week 24. The reference Hb was calculated from the mean of Hb concentrations based upon the Hb assessments at Weeks -4, -3, -2, -1, and 0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Maintaining Hemoglobin Concentration Within the Range of 10.5-12.5 g/dL Throughout the EEP | EEP (Week 17 to Week 24) | Percentage of participants maintaining Hb concentration within the range of 10.5-12.5 g/dL throughout the EEP is reported. The EEP was from Week 17 to Week 24. |
| Mean Time Spent By Participants With Hemoglobin Range of 10.5-12.5 g/dL During the EEP | EEP (Week 17 to Week 24) | Mean time spent by participants in Hb range of 10.5-12.5 g/dL during the EEP is reported. The EEP was from Week 17 to Week 24. |
| Number of Participants With Any Adverse Events or Serious Adverse Events | Up to Week 52 | An adverse event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAEs) is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, and congenital anomaly. |
| Mean Change From Baseline in Weight Over Time | Week 16 and Week 48 | Mean change in weight was defined as the difference between mean weight at Baseline and following visits (Week 16 and Week 48). |
| Percentage of Participants Requiring Any Dose Adjustment During DTP and EEP | DTP (Week 1 to Week 16) and EEP (Week 17 to Week 24) | Percentage of participants requiring any dose adjustment during DTP (Week 1 to Week 16) and EEP (Week 17 to Week 24) is reported. The dose adjustments (increase or decrease) were required: if a single Hb concentration was either \> or = 13 g/dL or \< or = 9 g/dL; if the difference of 2 consecutive Hb concentrations was \> or =2 g/dL; if the values of scheduled Hb assessments on the day of administration of C.E.R.A. and on the previous study visit were both out of range of 10.5 to 11.5 g/dL, the difference between the reference value (mean of Hb concentrations based on the Hb assessments at Weeks -4, -3, -2, -1, and 0) and the most recent value was \>1 g/dL; if the values of the scheduled Hb assessments on the day of administration of C.E.R.A. and on the previous study visit were both out of the range 10 to 12 g/dL. Dose adjustment could be made at any time at the discretion of the clinician if clinically warranted. |
| Incidences of Red Blood Cell Transfusions During the C.E.R.A. Treatment Phase | Up to Week 52 | Red Blood Cells (RBCs) transfusions were given during the treatment period in case of medical need. Blood transfusions occurred during the DTP, EEP, and during the long term safety period (LTSP) were reported. |
| Mean Hemoglobin Levels Over Time | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | The Hb levels were recorded for each participant at enrolment and at different time points during the study up to Week 48. |
| Mean Hematocrit Levels Over Time | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | The hematocrit (HCT) levels were recorded for each participant at enrolment and at different time points during the study up to Week 48. |
| Mean Change in Hemoglobin Concentration Between Reference (Stability Verification Period) and the Efficacy Evaluation Period | SVP (Weeks -3, -2, -1) and EEP (Week 17 to Week 24) | Mean change in Hb concentration between reference SVP and the EEP is reported. The SVP was at Weeks -3, -2, -1, and EEP was from Week 17 to Week 24. Participants received epoetin alfa or beta during SVP. |
| Mean White Blood Cells and Thrombocytes Over Time | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | The white blood cells (WBCs) and thrombocyte levels were recorded for each participant at enrolment and at different time points during the study up to Week 48. |
| Mean Phosphate and Potassium Levels Over Time | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | The phosphate and potassium levels were recorded for each participant at enrolment and at different time points during the study up to Week 48. |
| Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | The mean creatinine, iron, and total iron binding capacity (TIBC) levels over time were recorded for each participant at enrolment and at different time points during the study up to Week 48. |
| Mean C-Reactive Protein Levels Over Time | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | The mean C-Reactive Protein (CRP) Levels over time were recorded for each participant at enrolment and at different time points during the study up to Week 48. |
| Mean Ferritin Levels Over Time | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | The mean ferritin levels over time were recorded for each participant at enrolment and at different time points during the study up to Week 48. |
| Mean Transferrin Saturation Levels Over Time | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | The mean transferrin saturation (TSAT) levels over time were recorded for each participant at enrolment and at different time points during the study up to Week 48. |
| Mean Change From Baseline in Pulse Rate Over Time | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | Mean change in pulse rate was defined as the difference between mean pulse rate at Baseline and following visits (Weeks 8, 16, 24, 32, 40, and 48). |
| Mean Change From Baseline in Blood Pressure Over Time | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | Mean change in blood pressure (systolic blood pressure \[SBP\] and diastolic blood pressure \[DBP\]) before and after dialysis was defined as the difference between mean blood pressure at Baseline and following visits (Weeks 8, 16, 24, 32, 40, and 48). |
| Mean Albumin Levels Over Time | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | The albumin levels were recorded for each participant at enrolment and at different time points during the study up to Week 48. |
Countries
Morocco
Participant flow
Recruitment details
A total of 202 participants were enrolled in this study conducted from 12 February 2009 to 25 October 2010 at 28 study sites in Morocco.
Pre-assignment details
Of 202 participants, 8 participants did not complete the stability verification period (SVP) of 4 weeks. Overall, 194 participants entered dose titration period (DTP) of 16 weeks.
Participants by arm
| Arm | Count |
|---|---|
| C.E.R.A. Eligible participants were administered C.E.R.A. intravenously (IV) every 4 weeks for 44 weeks. The starting dose of C.E.R.A. (120, 200, or 360 micrograms \[mcg\]) was based on the dose of epoetin alfa or beta administered in the week preceding the switch to C.E.R.A. Subsequent doses were adjusted to maintain the individual participant's hemoglobin (Hb) value within a range of +/- 1.0 grams per deciliter (g/dL) of the reference Hb concentration and between 10.50 and 12.50 g/dL. | 194 |
| Total | 194 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative reasons | 4 |
| Overall Study | Adverse Event | 2 |
| Overall Study | Blood transfusion | 2 |
| Overall Study | Death | 3 |
| Overall Study | Failure to return | 2 |
| Overall Study | Insufficient therapeutic response | 3 |
| Overall Study | Other - Reasons | 2 |
| Overall Study | refused treatment/withdrew consent | 4 |
Baseline characteristics
| Characteristic | C.E.R.A. |
|---|---|
| Age, Continuous | 51.5 years |
| Sex: Female, Male Female | 76 Participants |
| Sex: Female, Male Male | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 194 |
| serious Total, serious adverse events | 19 / 194 |
Outcome results
Primary
Percentage of Participants Maintaining Mean Hemoglobin Concentration Within +/- 1 g/dL of Their Reference Hb and Between 10.5 and 12.5 g/dL During Efficacy Evaluation Period
The percentage of participants who maintained their mean Hb concentration within +/- 1 g/dL of their reference Hb and between 10.5 and 12.5 g/dL during the Efficacy Evaluation Period (EEP) is reported. The EEP was from Week 17 to Week 24. The reference Hb was calculated from the mean of Hb concentrations based upon the Hb assessments at Weeks -4, -3, -2, -1, and 0.
Time frame: EEP (Week 17 to Week 24)
Population: The per-protocol (PP) population included all participants from the intention-to-treat (ITT) population, who fulfilled inclusion/exclusion criteria as per the study protocol. A total of 123 participants were included in the PP population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A. | Percentage of Participants Maintaining Mean Hemoglobin Concentration Within +/- 1 g/dL of Their Reference Hb and Between 10.5 and 12.5 g/dL During Efficacy Evaluation Period | 52.0 Percentage of participants |
Secondary
Incidences of Red Blood Cell Transfusions During the C.E.R.A. Treatment Phase
Red Blood Cells (RBCs) transfusions were given during the treatment period in case of medical need. Blood transfusions occurred during the DTP, EEP, and during the long term safety period (LTSP) were reported.
Time frame: Up to Week 52
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C.E.R.A. | Incidences of Red Blood Cell Transfusions During the C.E.R.A. Treatment Phase | During DTP | 3 Number of RBCs transfusion |
| C.E.R.A. | Incidences of Red Blood Cell Transfusions During the C.E.R.A. Treatment Phase | During EEP | 1 Number of RBCs transfusion |
| C.E.R.A. | Incidences of Red Blood Cell Transfusions During the C.E.R.A. Treatment Phase | During LTSP | 2 Number of RBCs transfusion |
Secondary
Mean Albumin Levels Over Time
The albumin levels were recorded for each participant at enrolment and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who have been treated with at least one dose of the study drug and a safety follow-up, whether withdrawn prematurely or not. Out of 194, one participant was excluded from the ITT population due to missing hemoglobin measurement and C.E.R.A medication after Week 0.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A. | Mean Albumin Levels Over Time | Albumin at Week 0 (n = 193) | 43.1 g/L | Standard Deviation 8.61 |
| C.E.R.A. | Mean Albumin Levels Over Time | Albumin at Week 8 (n = 139) | 41.0 g/L | Standard Deviation 6.65 |
| C.E.R.A. | Mean Albumin Levels Over Time | Albumin at Week 16 (n = 130) | 41.3 g/L | Standard Deviation 6.44 |
| C.E.R.A. | Mean Albumin Levels Over Time | Albumin at Week 24 (n = 128) | 40.2 g/L | Standard Deviation 6.19 |
| C.E.R.A. | Mean Albumin Levels Over Time | Albumin at Week 32 (n = 116) | 39.9 g/L | Standard Deviation 6.12 |
| C.E.R.A. | Mean Albumin Levels Over Time | Albumin at Week 40 (n = 108) | 40.4 g/L | Standard Deviation 6.47 |
| C.E.R.A. | Mean Albumin Levels Over Time | Albumin at Week 48 (n = 147) | 39.9 g/L | Standard Deviation 7.26 |
Secondary
Mean Change From Baseline in Blood Pressure Over Time
Mean change in blood pressure (systolic blood pressure \[SBP\] and diastolic blood pressure \[DBP\]) before and after dialysis was defined as the difference between mean blood pressure at Baseline and following visits (Weeks 8, 16, 24, 32, 40, and 48).
Time frame: Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not. Participants with available data at the time of evaluation were analyzed. Number of participants with available data at specified period is denoted by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | DBP after dialysis at Week 8 (n = 185) | -0.40 millimeter of mercury | Standard Deviation 9.04 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | SBP before dialysis at Week 8 (n = 189) | 1.15 millimeter of mercury | Standard Deviation 14.41 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | SBP before dialysis at Week 16 (n = 185) | -0.78 millimeter of mercury | Standard Deviation 13.08 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | SBP before dialysis at Week 24 (n = 182) | -0.58 millimeter of mercury | Standard Deviation 13.14 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | SBP before dialysis at Week 32 (n = 181) | -1.28 millimeter of mercury | Standard Deviation 14.68 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | SBP before dialysis at Week 40 (n = 175) | 0.27 millimeter of mercury | Standard Deviation 13.24 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | SBP before dialysis at Week 48 (n = 191) | -0.52 millimeter of mercury | Standard Deviation 13.72 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | SBP after dialysis at Week 8 (n = 185) | 1.68 millimeter of mercury | Standard Deviation 12.62 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | SBP after dialysis at Week 16 (n = 181) | 0.48 millimeter of mercury | Standard Deviation 12.94 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | SBP after dialysis at Week 24 (n = 178) | 0.60 millimeter of mercury | Standard Deviation 13.1 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | SBP after dialysis at Week 32 (n = 177) | 0.40 millimeter of mercury | Standard Deviation 14.45 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | SBP after dialysis at Week 40 (n = 171) | 1.22 millimeter of mercury | Standard Deviation 11.97 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | SBP after dialysis at Week 48 (n = 187) | 1.63 millimeter of mercury | Standard Deviation 13.97 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | DBP before dialysis at Week 8 (n = 189) | -0.77 millimeter of mercury | Standard Deviation 11.85 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | DBP before dialysis at Week 16 (n = 185) | -1.87 millimeter of mercury | Standard Deviation 11 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | DBP before dialysis at Week 24 (n = 182) | -1.58 millimeter of mercury | Standard Deviation 11.56 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | DBP before dialysis at Week 32 (n = 181) | -2.08 millimeter of mercury | Standard Deviation 9.56 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | DBP before dialysis at Week 40 (n = 175) | -1.35 millimeter of mercury | Standard Deviation 10.23 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | DBP before dialysis at Week 48 (n = 191) | -0.90 millimeter of mercury | Standard Deviation 10.72 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | DBP after dialysis at Week 16 (n = 181) | -0.11 millimeter of mercury | Standard Deviation 10.35 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | DBP after dialysis at Week 24 (n = 178) | -0.90 millimeter of mercury | Standard Deviation 9.47 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | DBP after dialysis at Week 32 (n = 177) | -1.07 millimeter of mercury | Standard Deviation 8.56 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | DBP after dialysis at Week 40 (n = 171) | -1.50 millimeter of mercury | Standard Deviation 8.95 |
| C.E.R.A. | Mean Change From Baseline in Blood Pressure Over Time | DBP after dialysis at Week 48 (n = 187) | -1.21 millimeter of mercury | Standard Deviation 10.11 |
Secondary
Mean Change From Baseline in Pulse Rate Over Time
Mean change in pulse rate was defined as the difference between mean pulse rate at Baseline and following visits (Weeks 8, 16, 24, 32, 40, and 48).
Time frame: Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not. Participants with available data at the time of evaluation were analyzed. Number of participants with available data at specified period is denoted by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A. | Mean Change From Baseline in Pulse Rate Over Time | Week 8 (n = 175) | 0.37 beats per minute | Standard Deviation 6.21 |
| C.E.R.A. | Mean Change From Baseline in Pulse Rate Over Time | Week 16 (n = 175) | 0.02 beats per minute | Standard Deviation 6.61 |
| C.E.R.A. | Mean Change From Baseline in Pulse Rate Over Time | Week 24 (n = 173) | 0.30 beats per minute | Standard Deviation 6.86 |
| C.E.R.A. | Mean Change From Baseline in Pulse Rate Over Time | Week 32 (n = 173) | 0.40 beats per minute | Standard Deviation 6.97 |
| C.E.R.A. | Mean Change From Baseline in Pulse Rate Over Time | Week 40 (n = 174) | 0.52 beats per minute | Standard Deviation 8.24 |
| C.E.R.A. | Mean Change From Baseline in Pulse Rate Over Time | Week 48 (n = 190) | 0.76 beats per minute | Standard Deviation 8.69 |
Secondary
Mean Change From Baseline in Weight Over Time
Mean change in weight was defined as the difference between mean weight at Baseline and following visits (Week 16 and Week 48).
Time frame: Week 16 and Week 48
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not. Participants with available data at the time of evaluation were analyzed. Number of participants with available data at specified period is denoted by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A. | Mean Change From Baseline in Weight Over Time | Week 16 (n = 185) | -0.20 kilogram | Standard Deviation 3.17 |
| C.E.R.A. | Mean Change From Baseline in Weight Over Time | Week 48 (n = 191) | 0.06 kilogram | Standard Deviation 3.21 |
Secondary
Mean Change in Hemoglobin Concentration Between Reference (Stability Verification Period) and the Efficacy Evaluation Period
Mean change in Hb concentration between reference SVP and the EEP is reported. The SVP was at Weeks -3, -2, -1, and EEP was from Week 17 to Week 24. Participants received epoetin alfa or beta during SVP.
Time frame: SVP (Weeks -3, -2, -1) and EEP (Week 17 to Week 24)
Population: ITT population included all the participants who had received at least one dose of C.E.R.A. (Week 0) and for whom data for at least one follow-up variable (laboratory data, adverse events, etc.) was available. Out of 194 participants, one was excluded from the ITT population due to missing Hb measurement and C.E.R.A drug after Week 0.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C.E.R.A. | Mean Change in Hemoglobin Concentration Between Reference (Stability Verification Period) and the Efficacy Evaluation Period | 0.48 g/dL | Standard Deviation 1.05 |
Secondary
Mean C-Reactive Protein Levels Over Time
The mean C-Reactive Protein (CRP) Levels over time were recorded for each participant at enrolment and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not. Number of participants with available data at specified period is denoted by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A. | Mean C-Reactive Protein Levels Over Time | CRP at Week 0 (n = 190) | 6.9 miligrams/L | Standard Deviation 8.84 |
| C.E.R.A. | Mean C-Reactive Protein Levels Over Time | CRP at Week 8 (n = 139) | 7.9 miligrams/L | Standard Deviation 8.98 |
| C.E.R.A. | Mean C-Reactive Protein Levels Over Time | CRP at Week 16 (n = 130) | 8.6 miligrams/L | Standard Deviation 11.19 |
| C.E.R.A. | Mean C-Reactive Protein Levels Over Time | CRP at Week 24 (n = 127) | 9.3 miligrams/L | Standard Deviation 13.87 |
| C.E.R.A. | Mean C-Reactive Protein Levels Over Time | CRP at Week 32 (n = 112) | 7.1 miligrams/L | Standard Deviation 7.33 |
| C.E.R.A. | Mean C-Reactive Protein Levels Over Time | CRP at Week 40 (n = 109) | 7.2 miligrams/L | Standard Deviation 7.77 |
| C.E.R.A. | Mean C-Reactive Protein Levels Over Time | CRP at Week 48 (n = 140) | 7.4 miligrams/L | Standard Deviation 8.76 |
Secondary
Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time
The mean creatinine, iron, and total iron binding capacity (TIBC) levels over time were recorded for each participant at enrolment and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not. Number of participants with available data at specified period is denoted by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Creatinine at Week 0 (n = 194) | 775.7 micromole/L | Standard Deviation 477.8 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Creatinine at Week 8 (n = 139) | 692.5 micromole/L | Standard Deviation 502.86 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Creatinine at Week 16 (n = 130) | 676.1 micromole/L | Standard Deviation 490.8 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Creatinine at Week 24 (n = 130) | 683.7 micromole/L | Standard Deviation 472.92 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Creatinine at Week 32 (n = 117) | 670.2 micromole/L | Standard Deviation 477.22 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Creatinine at Week 40 (n = 110) | 674.8 micromole/L | Standard Deviation 488.26 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Creatinine at Week 48 (n = 149) | 699.6 micromole/L | Standard Deviation 444.93 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Iron at Week 0 (n = 194) | 15.9 micromole/L | Standard Deviation 8.04 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Iron at Week 8 (n = 139) | 15.1 micromole/L | Standard Deviation 7.49 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Iron at Week 16 (n = 129) | 15.1 micromole/L | Standard Deviation 6.74 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Iron at Week 24 (n = 130) | 14.3 micromole/L | Standard Deviation 5.08 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Iron at Week 32 (n = 116) | 14.9 micromole/L | Standard Deviation 5.5 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Iron at Week 40 (n = 110) | 15.6 micromole/L | Standard Deviation 5.59 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | Iron at Week 48 (n = 148) | 15.2 micromole/L | Standard Deviation 5.92 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | TIBC at Week 0 (n = 194) | 44.5 micromole/L | Standard Deviation 11.46 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | TIBC at Week 8 (n = 137) | 44.2 micromole/L | Standard Deviation 10.9 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | TIBC at Week 16 (n = 126) | 44.8 micromole/L | Standard Deviation 12.4 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | TIBC at Week 24 (n = 123) | 43.7 micromole/L | Standard Deviation 11.1 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | TIBC at Week 32 (n = 116) | 44.1 micromole/L | Standard Deviation 11.33 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | TIBC at Week 40 (n = 110) | 42.6 micromole/L | Standard Deviation 10.58 |
| C.E.R.A. | Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | TIBC at Week 48 (n = 147) | 44.0 micromole/L | Standard Deviation 10.37 |
Secondary
Mean Ferritin Levels Over Time
The mean ferritin levels over time were recorded for each participant at enrolment and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not. Number of participants with available data at specified period is denoted by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A. | Mean Ferritin Levels Over Time | Ferritin at Week 0 (n = 194) | 547.6 mcg/L | Standard Deviation 896.63 |
| C.E.R.A. | Mean Ferritin Levels Over Time | Ferritin at Week 8 (n = 138) | 522.2 mcg/L | Standard Deviation 772.16 |
| C.E.R.A. | Mean Ferritin Levels Over Time | Ferritin at Week 16 (n = 129) | 517.6 mcg/L | Standard Deviation 639.09 |
| C.E.R.A. | Mean Ferritin Levels Over Time | Ferritin at Week 24 (n = 128) | 508.6 mcg/L | Standard Deviation 577.75 |
| C.E.R.A. | Mean Ferritin Levels Over Time | Ferritin at Week 32 (n = 116) | 522.6 mcg/L | Standard Deviation 874.94 |
| C.E.R.A. | Mean Ferritin Levels Over Time | Ferritin at Week 40 (n = 110) | 562.8 mcg/L | Standard Deviation 984.72 |
| C.E.R.A. | Mean Ferritin Levels Over Time | Ferritin at Week 48 (n = 148) | 505.6 mcg/L | Standard Deviation 770.48 |
Secondary
Mean Hematocrit Levels Over Time
The hematocrit (HCT) levels were recorded for each participant at enrolment and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not. Number of participants with available data at specified period is denoted by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A. | Mean Hematocrit Levels Over Time | HCT at Week 0 (n = 194) | 0.34 Proportion of red blood cells in blood | Standard Deviation 0.02 |
| C.E.R.A. | Mean Hematocrit Levels Over Time | HCT at Week 8 (n = 184) | 0.36 Proportion of red blood cells in blood | Standard Deviation 0.04 |
| C.E.R.A. | Mean Hematocrit Levels Over Time | HCT at Week 16 (n = 175) | 0.36 Proportion of red blood cells in blood | Standard Deviation 0.04 |
| C.E.R.A. | Mean Hematocrit Levels Over Time | HCT at Week 24 (n = 180) | 0.36 Proportion of red blood cells in blood | Standard Deviation 0.04 |
| C.E.R.A. | Mean Hematocrit Levels Over Time | HCT at Week 32 (n = 177) | 0.36 Proportion of red blood cells in blood | Standard Deviation 0.04 |
| C.E.R.A. | Mean Hematocrit Levels Over Time | HCT at Week 40 (n = 163) | 0.36 Proportion of red blood cells in blood | Standard Deviation 0.04 |
| C.E.R.A. | Mean Hematocrit Levels Over Time | HCT at Week 48 (n = 170) | 0.35 Proportion of red blood cells in blood | Standard Deviation 0.04 |
Secondary
Mean Hemoglobin Levels Over Time
The Hb levels were recorded for each participant at enrolment and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not. Number of participants with available data at specified period is denoted by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A. | Mean Hemoglobin Levels Over Time | Hb at Week 0 (n = 194) | 11.2 g/dL | Standard Deviation 0.58 |
| C.E.R.A. | Mean Hemoglobin Levels Over Time | Hb at Week 8 (n = 184) | 11.7 g/dL | Standard Deviation 1.35 |
| C.E.R.A. | Mean Hemoglobin Levels Over Time | Hb at Week 16 (n = 175) | 11.8 g/dL | Standard Deviation 1.21 |
| C.E.R.A. | Mean Hemoglobin Levels Over Time | Hb at Week 24 (n = 180) | 11.8 g/dL | Standard Deviation 1.14 |
| C.E.R.A. | Mean Hemoglobin Levels Over Time | Hb at Week 32 (n = 177) | 11.8 g/dL | Standard Deviation 1.23 |
| C.E.R.A. | Mean Hemoglobin Levels Over Time | Hb at Week 40 (n = 162) | 11.8 g/dL | Standard Deviation 1.23 |
| C.E.R.A. | Mean Hemoglobin Levels Over Time | Hb at Week 48 (n = 168) | 11.6 g/dL | Standard Deviation 1.2 |
Secondary
Mean Phosphate and Potassium Levels Over Time
The phosphate and potassium levels were recorded for each participant at enrolment and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not. Number of participants with available data at specified period is denoted by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Potassium at Week 40 (n = 110) | 5.5 milimole/L | Standard Deviation 0.93 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Phosphate at Week 0 (n = 194) | 1.7 milimole/L | Standard Deviation 0.57 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Phosphate at Week 8 (n = 139) | 1.7 milimole/L | Standard Deviation 0.76 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Phosphate at Week 16 (n = 131) | 1.7 milimole/L | Standard Deviation 0.75 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Phosphate at Week 24 (n = 130) | 1.7 milimole/L | Standard Deviation 0.7 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Phosphate at Week 32 (n = 116) | 1.6 milimole/L | Standard Deviation 0.56 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Phosphate at Week 40 (n = 110) | 1.4 milimole/L | Standard Deviation 0.44 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Phosphate at Week 48 (n = 148) | 1.6 milimole/L | Standard Deviation 0.61 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Potassium at Week 0 (n = 194) | 5.3 milimole/L | Standard Deviation 0.91 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Potassium at Week 8 (n = 139) | 5.4 milimole/L | Standard Deviation 0.95 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Potassium at Week 16 (n = 131) | 5.4 milimole/L | Standard Deviation 0.99 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Potassium at Week 24 (n = 130) | 5.5 milimole/L | Standard Deviation 1.02 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Potassium at Week 32 (n = 117) | 5.5 milimole/L | Standard Deviation 0.92 |
| C.E.R.A. | Mean Phosphate and Potassium Levels Over Time | Potassium at Week 48 (n = 146) | 5.3 milimole/L | Standard Deviation 0.92 |
Secondary
Mean Time Spent By Participants With Hemoglobin Range of 10.5-12.5 g/dL During the EEP
Mean time spent by participants in Hb range of 10.5-12.5 g/dL during the EEP is reported. The EEP was from Week 17 to Week 24.
Time frame: EEP (Week 17 to Week 24)
Population: ITT population included all the participants who had received at least one dose of C.E.R.A. (Week 0) and for whom data for at least one follow-up variable (laboratory data, adverse events, etc.) was available. Out of 194 participants, one was excluded from the ITT population due to missing Hb measurement and C.E.R.A drug after Week 0.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C.E.R.A. | Mean Time Spent By Participants With Hemoglobin Range of 10.5-12.5 g/dL During the EEP | 35.1 Days | Standard Deviation 19.85 |
Secondary
Mean Transferrin Saturation Levels Over Time
The mean transferrin saturation (TSAT) levels over time were recorded for each participant at enrolment and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not. Number of participants with available data at specified period is denoted by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A. | Mean Transferrin Saturation Levels Over Time | TSAT at Week 0 (n = 194) | 37.3 Percentage of Transferrin Saturation | Standard Deviation 20.16 |
| C.E.R.A. | Mean Transferrin Saturation Levels Over Time | TSAT at Week 8 (n = 136) | 35.0 Percentage of Transferrin Saturation | Standard Deviation 16.38 |
| C.E.R.A. | Mean Transferrin Saturation Levels Over Time | TSAT at Week 16 (n = 125) | 36.0 Percentage of Transferrin Saturation | Standard Deviation 18.45 |
| C.E.R.A. | Mean Transferrin Saturation Levels Over Time | TSAT at Week 24 (n = 123) | 34.9 Percentage of Transferrin Saturation | Standard Deviation 18.24 |
| C.E.R.A. | Mean Transferrin Saturation Levels Over Time | TSAT at Week 32 (n = 115) | 35.4 Percentage of Transferrin Saturation | Standard Deviation 14.72 |
| C.E.R.A. | Mean Transferrin Saturation Levels Over Time | TSAT at Week 40 (n = 110) | 38.0 Percentage of Transferrin Saturation | Standard Deviation 15.66 |
| C.E.R.A. | Mean Transferrin Saturation Levels Over Time | TSAT at Week 48 (n = 147) | 36.5 Percentage of Transferrin Saturation | Standard Deviation 17.56 |
Secondary
Mean White Blood Cells and Thrombocytes Over Time
The white blood cells (WBCs) and thrombocyte levels were recorded for each participant at enrolment and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not. Number of participants with available data at specified period is denoted by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | WBCs at Week 0 (n = 194) | 6.5 10^9 cells/L | Standard Deviation 1.75 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | WBCs at Week 8 (n = 153) | 6.5 10^9 cells/L | Standard Deviation 2 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | WBCs at Week 16 (n = 137) | 6.3 10^9 cells/L | Standard Deviation 1.71 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | WBCs at Week 24 (n = 138) | 6.4 10^9 cells/L | Standard Deviation 2 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | WBCs at Week 32 (n = 129) | 6.3 10^9 cells/L | Standard Deviation 1.81 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | WBCs at Week 40 (n = 123) | 6.3 10^9 cells/L | Standard Deviation 1.78 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | WBCs at Week 48 (n = 153) | 6.5 10^9 cells/L | Standard Deviation 1.74 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | Thrombocytes at Week 0 (n = 194) | 213.9 10^9 cells/L | Standard Deviation 68.51 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | Thrombocytes at Week 8 (n = 153) | 207.5 10^9 cells/L | Standard Deviation 65.64 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | Thrombocytes at Week 16 (n = 137) | 202.5 10^9 cells/L | Standard Deviation 58.62 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | Thrombocytes at Week 24 (n = 138) | 200.5 10^9 cells/L | Standard Deviation 55.74 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | Thrombocytes at Week 32 (n = 129) | 208.6 10^9 cells/L | Standard Deviation 69.5 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | Thrombocytes at Week 40 (n = 123) | 206.1 10^9 cells/L | Standard Deviation 68.12 |
| C.E.R.A. | Mean White Blood Cells and Thrombocytes Over Time | Thrombocytes at Week 48 (n = 153) | 204.7 10^9 cells/L | Standard Deviation 68.95 |
Secondary
Number of Participants With Any Adverse Events or Serious Adverse Events
An adverse event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAEs) is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, and congenital anomaly.
Time frame: Up to Week 52
Population: Safety population included all participants who have been treated with at least one dose of the study drug and completed a safety follow-up, whether withdrawn prematurely or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C.E.R.A. | Number of Participants With Any Adverse Events or Serious Adverse Events | Any AEs | 39 Participants |
| C.E.R.A. | Number of Participants With Any Adverse Events or Serious Adverse Events | Any SAEs | 19 Participants |
Secondary
Percentage of Participants Maintaining Hemoglobin Concentration Within the Range of 10.5-12.5 g/dL Throughout the EEP
Percentage of participants maintaining Hb concentration within the range of 10.5-12.5 g/dL throughout the EEP is reported. The EEP was from Week 17 to Week 24.
Time frame: EEP (Week 17 to Week 24)
Population: ITT population included all the participants who had received at least one dose of C.E.R.A. (Week 0) and for whom data for at least one follow-up variable (laboratory data, adverse events, etc.) was available. Out of 194 participants, one was excluded from the ITT population due to missing Hb measurement and C.E.R.A drug after Week 0.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A. | Percentage of Participants Maintaining Hemoglobin Concentration Within the Range of 10.5-12.5 g/dL Throughout the EEP | 60.6 Percentage of participants |
Secondary
Percentage of Participants Requiring Any Dose Adjustment During DTP and EEP
Percentage of participants requiring any dose adjustment during DTP (Week 1 to Week 16) and EEP (Week 17 to Week 24) is reported. The dose adjustments (increase or decrease) were required: if a single Hb concentration was either \> or = 13 g/dL or \< or = 9 g/dL; if the difference of 2 consecutive Hb concentrations was \> or =2 g/dL; if the values of scheduled Hb assessments on the day of administration of C.E.R.A. and on the previous study visit were both out of range of 10.5 to 11.5 g/dL, the difference between the reference value (mean of Hb concentrations based on the Hb assessments at Weeks -4, -3, -2, -1, and 0) and the most recent value was \>1 g/dL; if the values of the scheduled Hb assessments on the day of administration of C.E.R.A. and on the previous study visit were both out of the range 10 to 12 g/dL. Dose adjustment could be made at any time at the discretion of the clinician if clinically warranted.
Time frame: DTP (Week 1 to Week 16) and EEP (Week 17 to Week 24)
Population: ITT population included all the participants who had received at least one dose of C.E.R.A. (Week 0) and for whom data for at least one follow-up variable (laboratory data, adverse events, etc.) was available. Out of 194 participants, one was excluded from the ITT population due to missing Hb measurement and C.E.R.A drug after Week 0.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C.E.R.A. | Percentage of Participants Requiring Any Dose Adjustment During DTP and EEP | Dose adjustment during DTP (n = 193) | 56 Percentage of participants |
| C.E.R.A. | Percentage of Participants Requiring Any Dose Adjustment During DTP and EEP | Dose adjustment during EEP (n = 185) | 34.6 Percentage of participants |