Anemia
Conditions
Brief summary
This single arm study will evaluate the maintenance of hemoglobin levels, safety and tolerability of once-monthly intravenous administration of Mircera in dialysis patients with chronic renal anemia. Patients will receive intravenous Mircera (120, 200 or 360 micrograms) every four weeks depending on the previous dose of epoetin alfa administered in the week preceding first study drug administration. Patients will be treated for 12 weeks with follow up 2 weeks after the last treatment visit. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Interventions
DRUGmethoxy polyethylene glycol-epoetin beta [Mircera]
iv (120, 200 or 360 micrograms) every 4 weeks for 12 weeks.
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
* male or female patients, \>=18 years of age; * chronic renal anemia; * Hb concentration 10.5g/dL - 12.5g/dL; * continuous intravenous maintenance therapy with epoetin alfa at the same dosing interval during the previous 2 months.
Exclusion criteria
* blood transfusion within the previous 2 months; * poorly controlled hypertension; * significant acute or chronic bleeding; * active malignant disease; * congestive heart failure (NYHA Class IV).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Maintaining Mean Hemoglobin Levels Within the Target Range During the Last 4 Weeks of the Treatment Period (Weeks 8 to 12) | Weeks 8 to 12 (Last 4 weeks of treatment period) | Participants maintaining mean hemoglobin (Hb) concentration within the target range i.e. 10.0 - 12.0 gram per deciliter (g/dL) during last 4 weeks (Weeks 8 to 12) of treatment period (TP) were reported. Total duration for treatment period was 12 weeks. Stability verification period of 2-weeks was conducted before treatment period. The reference Hb concentrations were based upon the mean of the assessments at Weeks -2, -1 and Week 0. The target range for assessment was set at the reference value Hb +/- 1 g/dL but not \>12.0 g/dL and not \<10.0 g/dL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Time Participants Spent Having Hemoglobin Range of 10.0 to 12.0 g/dL | Up to Week 12 | Mean time participants spent having hemoglobin range of 10.0 to 12.0 g/dL was reported. The reference Hb concentrations were based upon the mean of the assessments at Weeks -2, -1 and Week 0. The target range for assessment was set at the reference value hemoglobin +/- 1 gram per deciliter but not \>12.0 g/dL and not \<10.0 g/dL. |
| Number of Participants With Treatment Emergent Adverse Events, Serious Adverse Events and Deaths | Up to Week 14 | Participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs) and deaths in the overall study were reported. An Adverse Event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Mean Change From Baseline in Heart Rate Over Time | From Baseline (Week -1) to Weeks 0, 1, 2, 4, 6, 8, 10, and 12 | Mean change from Baseline (Week -1) to end of the treatment (Week 12) in heart rate was reported. Baseline measure was considered as (Week -1) evaluation for this parameter. |
| Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | From Baseline (Week -2) to Weeks -1, 0, 1, 2, 4, 6, 8, 10, and 12 | Mean change from Baseline (Week -2) to end of the treatment (Week 12) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) before and after dialysis was reported. Baseline measure was considered as (Week -2) evaluation for this parameter. |
| Number of Participants With Abnormal Electrocardiogram | At Week -2 and Week 12 | Participants with abnormal electrocardiogram were reported. |
| Mean Values of White Blood Cells and Platelets Over Time | At Weeks -2, 4, 8, and 12 | Mean values of white blood cells (WBCs), and platelets at Weeks -2, 4, 8, and 12 were reported. |
| Mean Values of Hypochromic Red Blood Cells Over Time | At Weeks -2, 4, 8, and 12 | Mean values of hypochromic red blood cells (RBCs) at Weeks -2, 4, 8, and 12 were reported. |
| Mean Corpuscular Volume Levels Over Time | At Weeks -2, 4, 8, and 12 | Mean corpuscular volume (MCV) is a measure of the average red blood cell volume. MCV levels at Weeks -2, 4, 8, and 12 were reported. |
| Mean Hemoglobin Concentration Between Stability Verification Period (Weeks -2 to -1) and Treatment Period (Weeks 8 to 12) | SVP (Weeks -2 to -1) and TP (Weeks 8 to 12) | The mean change in Hb concentration between reference stability verification period (SVP) and in last 4 weeks (Weeks 8 to 12) of treatment period (TP) was reported. Duration for SVP was 2 weeks followed by treatment period of 12 weeks. The reference Hb concentrations were based upon the mean of the assessments at Weeks -2, -1 and Week 0. The target range for assessment was set at the reference value hemoglobin +/- 1 g/dL but not \>12.0 g/dL and not \<10.0 g/dL. |
| Mean Values of Serum Ferritin Over Time | At Weeks -2, 4, 8, and 12 | Mean values of serum ferritin were reported. |
| Mean Values of Transferrin Over Time | At Weeks -2, 4, 8, and 12 | Mean values of transferrin were reported. |
| Mean Values of Transferrin Saturation Over Time | At Weeks -2, 4, 8, and 12 | Mean values of Transferrin Saturation (TSAT) were reported. |
| Mean Values of Serum Albumin and Serum Globulin Over Time | At Weeks -2, 4, 8, and 12 | Mean values of serum albumin and serum globulin were reported. |
| Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | At Weeks -2, 4, 8, and 12 | Mean values of aspartate aminotransferase (AST), alanine transaminase (ALT) and serum alkaline phosphatase were reported. |
| Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | At Weeks -2, 4, 8, and 12 | Mean values of serum creatinine, blood urea nitrogen (BUN), serum phosphate and serum bilirubin were reported. |
| Mean Values of Serum Sodium and Serum Potassium Over Time | At Weeks -2, 4, 8, and 12 | Mean values of serum sodium and serum potassium were reported. |
| Mean Values of Iron Parameters (Serum Iron and Total Iron Binding Capacity) Over Time | At Weeks -2, 4, 8, and 12 | Mean values of serum iron and total iron binding capacity (TIBC) were reported. |
Countries
India
Participant flow
Recruitment details
A total of 132 participants were enrolled from 26 August 2008 to 12 September 2009 at 11 study sites in India.
Participants by arm
| Arm | Count |
|---|---|
| Mircera Eligible participants with chronic renal anemia were administered methoxy polyethylene glycol-epoetin beta \[Mircera\] intravenously (IV) \[(120, 200 or 360 micrograms (mcg)\] every 4 weeks for 12 weeks. | 132 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 6 |
| Overall Study | Other - Failure to Return | 1 |
| Overall Study | Other reasons | 4 |
| Overall Study | Refused Treatment / Withdrew Consent | 6 |
Baseline characteristics
| Characteristic | Mircera |
|---|---|
| Age, Continuous | 52.74 years STANDARD_DEVIATION 12.4 |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 132 |
| serious Total, serious adverse events | 9 / 132 |
Outcome results
Primary
Percentage of Participants Maintaining Mean Hemoglobin Levels Within the Target Range During the Last 4 Weeks of the Treatment Period (Weeks 8 to 12)
Participants maintaining mean hemoglobin (Hb) concentration within the target range i.e. 10.0 - 12.0 gram per deciliter (g/dL) during last 4 weeks (Weeks 8 to 12) of treatment period (TP) were reported. Total duration for treatment period was 12 weeks. Stability verification period of 2-weeks was conducted before treatment period. The reference Hb concentrations were based upon the mean of the assessments at Weeks -2, -1 and Week 0. The target range for assessment was set at the reference value Hb +/- 1 g/dL but not \>12.0 g/dL and not \<10.0 g/dL.
Time frame: Weeks 8 to 12 (Last 4 weeks of treatment period)
Population: Per-protocol (PP) population comprised of participants who had received at least 1 dose of MIRCERA (Week 0) and for whom data for at least one follow-up variable was available and who had completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mircera | Percentage of Participants Maintaining Mean Hemoglobin Levels Within the Target Range During the Last 4 Weeks of the Treatment Period (Weeks 8 to 12) | 57.89 Percentage of participants |
Secondary
Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time
Mean change from Baseline (Week -2) to end of the treatment (Week 12) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) before and after dialysis was reported. Baseline measure was considered as (Week -2) evaluation for this parameter.
Time frame: From Baseline (Week -2) to Weeks -1, 0, 1, 2, 4, 6, 8, 10, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = the number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week-2, Before Dialysis (n = 132) | 145.04 mmHg | Standard Deviation 15.71 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week-2, After Dialysis (n = 131) | 145.51 mmHg | Standard Deviation 18.12 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week-1, Before Dialysis (n = 132) | 146.72 mmHg | Standard Deviation 14.77 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week-1, After Dialysis (n =131) | 143.26 mmHg | Standard Deviation 18.72 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 0, Before Dialysis (n = 131) | 145.05 mmHg | Standard Deviation 16.04 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 0, After Dialysis (n = 130) | 143.75 mmHg | Standard Deviation 16.96 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 1, Before Dialysis (n = 129) | 147.02 mmHg | Standard Deviation 17.4 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 1, After Dialysis (n = 128) | 144.02 mmHg | Standard Deviation 17.68 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 2, Before Dialysis (n = 124) | 146.85 mmHg | Standard Deviation 18.08 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 2, After Dialysis (n = 123) | 144.92 mmHg | Standard Deviation 18.44 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 4, Before Dialysis (n = 124) | 146.68 mmHg | Standard Deviation 16.98 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 4, After Dialysis (n = 124) | 143.65 mmHg | Standard Deviation 18.18 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 6, Before Dialysis (n = 121) | 145.16 mmHg | Standard Deviation 18.58 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 6, After Dialysis (n = 121) | 145.55 mmHg | Standard Deviation 20.64 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 8, Before Dialysis (n = 118) | 144.77 mmHg | Standard Deviation 18.84 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 8, After Dialysis (n = 118) | 143.42 mmHg | Standard Deviation 17.14 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 10, Before Dialysis (n = 115) | 144.14 mmHg | Standard Deviation 17.57 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 10, After Dialysis (n = 115) | 143.98 mmHg | Standard Deviation 17.44 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 12, Before Dialysis (n = 115) | 144.55 mmHg | Standard Deviation 18.46 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | SBP, Week 12, After Dialysis (n = 115) | 143.80 mmHg | Standard Deviation 18.22 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week -2, Before Dialysis (n = 132) | 82.92 mmHg | Standard Deviation 9.32 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week -2, After Dialysis (n = 131) | 84.05 mmHg | Standard Deviation 9.4 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week -1, Before Dialysis (n = 132) | 83.90 mmHg | Standard Deviation 9.8 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week -1, After Dialysis (n = 131) | 83.22 mmHg | Standard Deviation 9.51 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 0, Before Dialysis (n = 131) | 84.05 mmHg | Standard Deviation 8.57 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 0, After Dialysis (n = 130) | 84.04 mmHg | Standard Deviation 8.94 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 1, Before Dialysis (n = 129) | 84.68 mmHg | Standard Deviation 9.34 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 1, After Dialysis (n = 128) | 83.27 mmHg | Standard Deviation 8.97 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 2, Before Dialysis (n = 124) | 83.77 mmHg | Standard Deviation 8.62 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 2, After Dialysis (n = 123) | 83.69 mmHg | Standard Deviation 8.85 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 4, Before Dialysis (n = 124) | 84.15 mmHg | Standard Deviation 8.98 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 4, After Dialysis (n = 124) | 83.29 mmHg | Standard Deviation 9.27 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 6, Before Dialysis (n = 121) | 83.31 mmHg | Standard Deviation 8.98 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 6, After Dialysis (n = 121) | 83.97 mmHg | Standard Deviation 9.24 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 8, Before Dialysis (n = 118) | 83.28 mmHg | Standard Deviation 9.49 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 8, After Dialysis (n = 118) | 84.35 mmHg | Standard Deviation 8.03 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 10, Before Dialysis (n = 115) | 83.91 mmHg | Standard Deviation 8.55 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 10, After Dialysis (n = 115) | 84.33 mmHg | Standard Deviation 9.24 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 12, Before Dialysis (n = 115) | 84.17 mmHg | Standard Deviation 10.47 |
| Mircera | Mean Change From Baseline in Blood Pressure (Systolic Blood Pressure and Diastolic Blood Pressure) Over Time | DBP, Week 12, After Dialysis (n = 115) | 83.23 mmHg | Standard Deviation 9.45 |
Secondary
Mean Change From Baseline in Heart Rate Over Time
Mean change from Baseline (Week -1) to end of the treatment (Week 12) in heart rate was reported. Baseline measure was considered as (Week -1) evaluation for this parameter.
Time frame: From Baseline (Week -1) to Weeks 0, 1, 2, 4, 6, 8, 10, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Change From Baseline in Heart Rate Over Time | Heart rate, Week -1, (n = 132) | 78.79 Beats per minute (bpm) | Standard Deviation 7.12 |
| Mircera | Mean Change From Baseline in Heart Rate Over Time | Heart rate, Week 0, (n = 131) | 79.54 Beats per minute (bpm) | Standard Deviation 7.27 |
| Mircera | Mean Change From Baseline in Heart Rate Over Time | Heart rate, Week 1, (n = 129) | 78.64 Beats per minute (bpm) | Standard Deviation 6.92 |
| Mircera | Mean Change From Baseline in Heart Rate Over Time | Heart rate, Week 2, (n = 124) | 78.98 Beats per minute (bpm) | Standard Deviation 7.83 |
| Mircera | Mean Change From Baseline in Heart Rate Over Time | Heart rate, Week 4, (n = 124) | 78.61 Beats per minute (bpm) | Standard Deviation 6.92 |
| Mircera | Mean Change From Baseline in Heart Rate Over Time | Heart rate, Week 6, (n = 121) | 79.55 Beats per minute (bpm) | Standard Deviation 8.37 |
| Mircera | Mean Change From Baseline in Heart Rate Over Time | Heart rate, Week 8, (n = 118) | 79.83 Beats per minute (bpm) | Standard Deviation 7.55 |
| Mircera | Mean Change From Baseline in Heart Rate Over Time | Heart rate, Week 10, (n = 115) | 79.56 Beats per minute (bpm) | Standard Deviation 7.54 |
| Mircera | Mean Change From Baseline in Heart Rate Over Time | Heart rate, Week 12, (n = 115) | 79.80 Beats per minute (bpm) | Standard Deviation 7.65 |
Secondary
Mean Corpuscular Volume Levels Over Time
Mean corpuscular volume (MCV) is a measure of the average red blood cell volume. MCV levels at Weeks -2, 4, 8, and 12 were reported.
Time frame: At Weeks -2, 4, 8, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Corpuscular Volume Levels Over Time | MCV, Week -2 (n = 125) | 90.32 femtoliters | Standard Deviation 7.32 |
| Mircera | Mean Corpuscular Volume Levels Over Time | MCV, Week 4 (n = 107) | 89.99 femtoliters | Standard Deviation 7.53 |
| Mircera | Mean Corpuscular Volume Levels Over Time | MCV, Week 8 (n = 112) | 89.41 femtoliters | Standard Deviation 7.04 |
| Mircera | Mean Corpuscular Volume Levels Over Time | MCV, Week 12 (n = 108) | 88.09 femtoliters | Standard Deviation 8.79 |
Secondary
Mean Hemoglobin Concentration Between Stability Verification Period (Weeks -2 to -1) and Treatment Period (Weeks 8 to 12)
The mean change in Hb concentration between reference stability verification period (SVP) and in last 4 weeks (Weeks 8 to 12) of treatment period (TP) was reported. Duration for SVP was 2 weeks followed by treatment period of 12 weeks. The reference Hb concentrations were based upon the mean of the assessments at Weeks -2, -1 and Week 0. The target range for assessment was set at the reference value hemoglobin +/- 1 g/dL but not \>12.0 g/dL and not \<10.0 g/dL.
Time frame: SVP (Weeks -2 to -1) and TP (Weeks 8 to 12)
Population: Per-protocol (PP) population comprised of participants who had received at least 1 dose of MIRCERA (Week 0) and for whom data for at least one follow-up variable was available and who had completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Hemoglobin Concentration Between Stability Verification Period (Weeks -2 to -1) and Treatment Period (Weeks 8 to 12) | Hb in SVP | 10.76 gm/dL | Standard Deviation 0.75 |
| Mircera | Mean Hemoglobin Concentration Between Stability Verification Period (Weeks -2 to -1) and Treatment Period (Weeks 8 to 12) | Avg of Hb in Last 4 Weeks TP | 11.28 gm/dL | Standard Deviation 1.22 |
Secondary
Mean Time Participants Spent Having Hemoglobin Range of 10.0 to 12.0 g/dL
Mean time participants spent having hemoglobin range of 10.0 to 12.0 g/dL was reported. The reference Hb concentrations were based upon the mean of the assessments at Weeks -2, -1 and Week 0. The target range for assessment was set at the reference value hemoglobin +/- 1 gram per deciliter but not \>12.0 g/dL and not \<10.0 g/dL.
Time frame: Up to Week 12
Population: Per-protocol (PP) population comprised of participants who had received at least 1 dose of MIRCERA (Week 0) and for whom data for at least one follow-up variable was available and who had completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mircera | Mean Time Participants Spent Having Hemoglobin Range of 10.0 to 12.0 g/dL | 3.15 Weeks | Standard Deviation 1 |
Secondary
Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time
Mean values of aspartate aminotransferase (AST), alanine transaminase (ALT) and serum alkaline phosphatase were reported.
Time frame: At Weeks -2, 4, 8, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | AST, Week -2 (n = 128) | 23.48 units per litre | Standard Deviation 18.45 |
| Mircera | Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | AST, Week 4 (n = 123) | 23.26 units per litre | Standard Deviation 12.87 |
| Mircera | Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | AST, Week 8 (n = 117) | 22.86 units per litre | Standard Deviation 15 |
| Mircera | Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | AST, Week 12 (n = 115) | 23.17 units per litre | Standard Deviation 15.69 |
| Mircera | Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | ALT, Week -2 (n = 129) | 31.34 units per litre | Standard Deviation 27.52 |
| Mircera | Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | ALT, Week 4 (n = 121) | 30.18 units per litre | Standard Deviation 18.82 |
| Mircera | Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | ALT, Week 8 (n = 118) | 29.44 units per litre | Standard Deviation 20.26 |
| Mircera | Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | ALT, Week 12 (n = 115) | 31.07 units per litre | Standard Deviation 20.71 |
| Mircera | Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | Serum Alkaline Phosphatase, Week -2 (n = 131) | 154.7 units per litre | Standard Deviation 110.6 |
| Mircera | Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | Serum Alkaline Phosphatase, Week 4 (n = 123) | 163.3 units per litre | Standard Deviation 108.9 |
| Mircera | Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | Serum Alkaline Phosphatase, Week 8 (n = 118) | 162.1 units per litre | Standard Deviation 123.4 |
| Mircera | Mean Values of Aspartate Aminotransferase, Alanine Transaminase and Serum Alkaline Phosphatase Over Time | Serum Alkaline Phosphatase, Week 12 (n = 115) | 159.3 units per litre | Standard Deviation 100.1 |
Secondary
Mean Values of Hypochromic Red Blood Cells Over Time
Mean values of hypochromic red blood cells (RBCs) at Weeks -2, 4, 8, and 12 were reported.
Time frame: At Weeks -2, 4, 8, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Values of Hypochromic Red Blood Cells Over Time | Hypochromic RBCs, Week -2 (n = 41) | 3.58 Percentage of RBCs | Standard Deviation 0.43 |
| Mircera | Mean Values of Hypochromic Red Blood Cells Over Time | Hypochromic RBCs, Week 4 (n = 34) | 3.73 Percentage of RBCs | Standard Deviation 0.57 |
| Mircera | Mean Values of Hypochromic Red Blood Cells Over Time | Hypochromic RBCs, Week 8 (n = 42) | 3.88 Percentage of RBCs | Standard Deviation 0.59 |
| Mircera | Mean Values of Hypochromic Red Blood Cells Over Time | Hypochromic RBCs, Week 12 (n = 42) | 3.97 Percentage of RBCs | Standard Deviation 0.73 |
Secondary
Mean Values of Iron Parameters (Serum Iron and Total Iron Binding Capacity) Over Time
Mean values of serum iron and total iron binding capacity (TIBC) were reported.
Time frame: At Weeks -2, 4, 8, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Values of Iron Parameters (Serum Iron and Total Iron Binding Capacity) Over Time | Serum Iron, Week -2 (n = 131) | 102.13 microgram per deciliter | Standard Deviation 77.47 |
| Mircera | Mean Values of Iron Parameters (Serum Iron and Total Iron Binding Capacity) Over Time | Serum Iron, Week 4 (n = 122) | 108.56 microgram per deciliter | Standard Deviation 59.65 |
| Mircera | Mean Values of Iron Parameters (Serum Iron and Total Iron Binding Capacity) Over Time | Serum Iron, Week 8 (n = 118) | 116.79 microgram per deciliter | Standard Deviation 67.96 |
| Mircera | Mean Values of Iron Parameters (Serum Iron and Total Iron Binding Capacity) Over Time | Serum Iron, Week 12 (n = 112) | 110.53 microgram per deciliter | Standard Deviation 56.31 |
| Mircera | Mean Values of Iron Parameters (Serum Iron and Total Iron Binding Capacity) Over Time | TIBC, Week -2 (n = 131) | 273.44 microgram per deciliter | Standard Deviation 114.36 |
| Mircera | Mean Values of Iron Parameters (Serum Iron and Total Iron Binding Capacity) Over Time | TIBC, Week 4 (n = 122) | 266.98 microgram per deciliter | Standard Deviation 116.69 |
| Mircera | Mean Values of Iron Parameters (Serum Iron and Total Iron Binding Capacity) Over Time | TIBC, Week 8 (n = 115) | 283.50 microgram per deciliter | Standard Deviation 133.49 |
| Mircera | Mean Values of Iron Parameters (Serum Iron and Total Iron Binding Capacity) Over Time | TIBC, Week 12 (n = 112) | 276.43 microgram per deciliter | Standard Deviation 118.54 |
Secondary
Mean Values of Serum Albumin and Serum Globulin Over Time
Mean values of serum albumin and serum globulin were reported.
Time frame: At Weeks -2, 4, 8, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Values of Serum Albumin and Serum Globulin Over Time | Serum Globulin, Week 12 (n = 113) | 3.51 gram per deciliter | Standard Deviation 0.67 |
| Mircera | Mean Values of Serum Albumin and Serum Globulin Over Time | Serum Albumin, Week -2 (n = 132) | 3.60 gram per deciliter | Standard Deviation 0.53 |
| Mircera | Mean Values of Serum Albumin and Serum Globulin Over Time | Serum Albumin, Week 4 (n = 123) | 3.54 gram per deciliter | Standard Deviation 0.42 |
| Mircera | Mean Values of Serum Albumin and Serum Globulin Over Time | Serum Albumin, Week 8 (n = 118) | 3.58 gram per deciliter | Standard Deviation 0.46 |
| Mircera | Mean Values of Serum Albumin and Serum Globulin Over Time | Serum Albumin, Week 12 (n = 115) | 3.64 gram per deciliter | Standard Deviation 0.46 |
| Mircera | Mean Values of Serum Albumin and Serum Globulin Over Time | Serum Globulin, Week -2 (n = 131) | 3.48 gram per deciliter | Standard Deviation 0.65 |
| Mircera | Mean Values of Serum Albumin and Serum Globulin Over Time | Serum Globulin, Week 4 (n = 123) | 3.41 gram per deciliter | Standard Deviation 0.68 |
| Mircera | Mean Values of Serum Albumin and Serum Globulin Over Time | Serum Globulin, Week 8 (n = 117) | 3.55 gram per deciliter | Standard Deviation 0.73 |
Secondary
Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time
Mean values of serum creatinine, blood urea nitrogen (BUN), serum phosphate and serum bilirubin were reported.
Time frame: At Weeks -2, 4, 8, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | BUN, Week 4 (n = 122) | 60.67 miligram per deciliter | Standard Deviation 27.7 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | Serum Creatinine, Week -2 (n = 132) | 7.89 miligram per deciliter | Standard Deviation 2.96 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | Serum Creatinine, Week 4 (n = 123) | 8.34 miligram per deciliter | Standard Deviation 2.47 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | Serum Creatinine, Week 8 (n = 116) | 8.03 miligram per deciliter | Standard Deviation 2.36 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | Serum Creatinine, Week 12 (n = 115) | 8.19 miligram per deciliter | Standard Deviation 2.72 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | BUN, Week -2 (n = 131) | 57.72 miligram per deciliter | Standard Deviation 29.71 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | BUN, Week 8 (n = 117) | 60.10 miligram per deciliter | Standard Deviation 32.04 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | BUN, Week 12 (n = 113) | 61.79 miligram per deciliter | Standard Deviation 35.14 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | Serum Phosphate, Week -2 (n = 124) | 5.00 miligram per deciliter | Standard Deviation 4.7 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | Serum Phosphate, Week 4 (n = 114) | 5.02 miligram per deciliter | Standard Deviation 1.93 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | Serum Phosphate, Week 8 (n = 112) | 4.81 miligram per deciliter | Standard Deviation 1.64 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | Serum Phosphate, Week 12 (n = 107) | 5.37 miligram per deciliter | Standard Deviation 5.22 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | Serum Bilirubin, Week -2 (n = 131) | 0.52 miligram per deciliter | Standard Deviation 0.34 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | Serum Bilirubin, Week 4 (n = 123) | 0.50 miligram per deciliter | Standard Deviation 0.33 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | Serum Bilirubin, Week 8 (n = 118) | 0.52 miligram per deciliter | Standard Deviation 0.43 |
| Mircera | Mean Values of Serum Creatinine, Blood Urea Nitrogen, Serum Phosphate and Serum Bilirubin Over Time | Serum Bilirubin, Week 12 (n = 115) | 0.51 miligram per deciliter | Standard Deviation 0.21 |
Secondary
Mean Values of Serum Ferritin Over Time
Mean values of serum ferritin were reported.
Time frame: At Weeks -2, 4, 8, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Values of Serum Ferritin Over Time | Serum Ferritin, Week -2 (n = 126) | 1806.30 nanogram per mililiter | Standard Deviation 6418.97 |
| Mircera | Mean Values of Serum Ferritin Over Time | Serum Ferritin, Week 4 (n = 117) | 1422.48 nanogram per mililiter | Standard Deviation 2550.43 |
| Mircera | Mean Values of Serum Ferritin Over Time | Serum Ferritin, Week 8 (n = 109) | 1109.07 nanogram per mililiter | Standard Deviation 1050.9 |
| Mircera | Mean Values of Serum Ferritin Over Time | Serum Ferritin, Week 12 (n = 105) | 1109.80 nanogram per mililiter | Standard Deviation 1016.17 |
Secondary
Mean Values of Serum Sodium and Serum Potassium Over Time
Mean values of serum sodium and serum potassium were reported.
Time frame: At Weeks -2, 4, 8, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Values of Serum Sodium and Serum Potassium Over Time | Serum Potassium, Week -2 (n = 132) | 5.00 millimole per liter | Standard Deviation 0.94 |
| Mircera | Mean Values of Serum Sodium and Serum Potassium Over Time | Serum Potassium, Week 4 (n = 123) | 6.26 millimole per liter | Standard Deviation 11.74 |
| Mircera | Mean Values of Serum Sodium and Serum Potassium Over Time | Serum Potassium, Week 8 (n = 118) | 5.11 millimole per liter | Standard Deviation 0.88 |
| Mircera | Mean Values of Serum Sodium and Serum Potassium Over Time | Serum Potassium, Week 12 (n = 115) | 5.03 millimole per liter | Standard Deviation 1.08 |
| Mircera | Mean Values of Serum Sodium and Serum Potassium Over Time | Serum Sodium, Week -2 (n = 132) | 137.1 millimole per liter | Standard Deviation 4.36 |
| Mircera | Mean Values of Serum Sodium and Serum Potassium Over Time | Serum Sodium, Week 4 (n = 122) | 136.2 millimole per liter | Standard Deviation 12.65 |
| Mircera | Mean Values of Serum Sodium and Serum Potassium Over Time | Serum Sodium, Week 8 (n = 118) | 137.0 millimole per liter | Standard Deviation 4.58 |
| Mircera | Mean Values of Serum Sodium and Serum Potassium Over Time | Serum Sodium, Week 12 (n = 115) | 136.9 millimole per liter | Standard Deviation 5.37 |
Secondary
Mean Values of Transferrin Over Time
Mean values of transferrin were reported.
Time frame: At Weeks -2, 4, 8, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Values of Transferrin Over Time | Transferrin, Week -2 (n = 25) | 168.24 miligram per mililiter | Standard Deviation 54.07 |
| Mircera | Mean Values of Transferrin Over Time | Transferrin, Week 4 (n = 16) | 160.00 miligram per mililiter | Standard Deviation 40.04 |
| Mircera | Mean Values of Transferrin Over Time | Transferrin, Week 8 (n = 18) | 165.72 miligram per mililiter | Standard Deviation 40.89 |
| Mircera | Mean Values of Transferrin Over Time | Transferrin, Week 12 (n = 18) | 159.22 miligram per mililiter | Standard Deviation 36.04 |
Secondary
Mean Values of Transferrin Saturation Over Time
Mean values of Transferrin Saturation (TSAT) were reported.
Time frame: At Weeks -2, 4, 8, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Values of Transferrin Saturation Over Time | TSAT, Week -2 (n = 125) | 45.55 Percentage | Standard Deviation 38.71 |
| Mircera | Mean Values of Transferrin Saturation Over Time | TSAT, Week 4 (n = 116) | 48.70 Percentage | Standard Deviation 36.31 |
| Mircera | Mean Values of Transferrin Saturation Over Time | TSAT, Week 8 (n = 109) | 46.08 Percentage | Standard Deviation 31.08 |
| Mircera | Mean Values of Transferrin Saturation Over Time | TSAT, Week 12 (n = 106) | 45.71 Percentage | Standard Deviation 29.81 |
Secondary
Mean Values of White Blood Cells and Platelets Over Time
Mean values of white blood cells (WBCs), and platelets at Weeks -2, 4, 8, and 12 were reported.
Time frame: At Weeks -2, 4, 8, and 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mircera | Mean Values of White Blood Cells and Platelets Over Time | WBCs, Week -2 (n = 132) | 7527.50 Per cubic millimeter | Standard Deviation 2444.43 |
| Mircera | Mean Values of White Blood Cells and Platelets Over Time | WBCs, Week 4 (n = 114) | 7369.74 Per cubic millimeter | Standard Deviation 2470.21 |
| Mircera | Mean Values of White Blood Cells and Platelets Over Time | WBCs, Week 8 (n = 118) | 7506.61 Per cubic millimeter | Standard Deviation 2214.38 |
| Mircera | Mean Values of White Blood Cells and Platelets Over Time | WBCs, Week 12 (n = 115) | 7484.35 Per cubic millimeter | Standard Deviation 2130.22 |
| Mircera | Mean Values of White Blood Cells and Platelets Over Time | Platelets, Week -2 (n = 132) | 211772.73 Per cubic millimeter | Standard Deviation 73360.93 |
| Mircera | Mean Values of White Blood Cells and Platelets Over Time | Platelets, Week 4 (n = 114) | 199508.77 Per cubic millimeter | Standard Deviation 64724.91 |
| Mircera | Mean Values of White Blood Cells and Platelets Over Time | Platelets, Week 8 (n = 118) | 208745.76 Per cubic millimeter | Standard Deviation 67546.15 |
| Mircera | Mean Values of White Blood Cells and Platelets Over Time | Platelets, Week 12 (n = 115) | 208566.37 Per cubic millimeter | Standard Deviation 102269.07 |
Secondary
Number of Participants With Abnormal Electrocardiogram
Participants with abnormal electrocardiogram were reported.
Time frame: At Week -2 and Week 12
Population: Safety population included all enrolled participants who received at least one dose of study drug. n = the number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mircera | Number of Participants With Abnormal Electrocardiogram | Week -2 (n=132) | 61 Number of participants |
| Mircera | Number of Participants With Abnormal Electrocardiogram | Week 12 (n=115) | 50 Number of participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events, Serious Adverse Events and Deaths
Participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs) and deaths in the overall study were reported. An Adverse Event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to Week 14
Population: Safety population included all enrolled participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mircera | Number of Participants With Treatment Emergent Adverse Events, Serious Adverse Events and Deaths | TEAEs | 27 Number of participants |
| Mircera | Number of Participants With Treatment Emergent Adverse Events, Serious Adverse Events and Deaths | SAEs | 9 Number of participants |
| Mircera | Number of Participants With Treatment Emergent Adverse Events, Serious Adverse Events and Deaths | Deaths | 3 Number of participants |