Trial Outcomes & Findings for A Study of Subcutaneous Mircera in Patients With Chronic Kidney Disease, Not on Dialysis. (NCT NCT00442702)

NCT ID: NCT00442702

Last Updated: 2011-12-19

Results Overview

A time adjusted average baseline hemoglobin (Hb) concentration was calculated using the trapezoid rule from all available Hb measurements taken during the baseline period. The average evaluation period Hb concentration for each individual was calculated using the same method, from all their available measurements taken during the two month evaluation period. The change in Hb concentration between the baseline and evaluation periods was calculated by subtracting the baseline Hb from the evaluation period Hb. All blood samples for Hb measurements were taken prior to study drug administration.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 228 participants
• Primary outcome timeframe: Baseline (measurements at Week -4, Week -2 and Day 1) and Evaluation Period (Months 8 and 9; measurements twice a month and at the final visit).
• Results posted on: 2011-12-19

Participant Flow

Participant milestones

Measure	Mircera Participants received Mircera by subcutaneous injection once every month during the dose titration (7 months) and evaluation period (2 months). The starting dose was based on the weekly dose of darbepoetin alfa administered prior to the switch to Mircera, and was either 120, 200 or 360 µg Mircera per month. The dose was then adjusted to maintain Hemoglobin levels within the defined target range and also according to the need for red blood cell transfusions (due to worsening anemia), or for toxicity related to Mircera.	Darbepoetin Alfa Participants continued to receive the same dose of darbepoetin alfa by subcutaneous injection once every week, once every 2 weeks or once every month as per local labeling during the dose titration (7 months) and the evaluation period (2 months).
Titration Period STARTED	114	114
Titration Period Safety Population	115	113
Titration Period COMPLETED	102	111
Titration Period NOT COMPLETED	12	3
Evaluation Period STARTED	102	111
Evaluation Period COMPLETED	97	107
Evaluation Period NOT COMPLETED	5	4

Reasons for withdrawal

Measure	Mircera Participants received Mircera by subcutaneous injection once every month during the dose titration (7 months) and evaluation period (2 months). The starting dose was based on the weekly dose of darbepoetin alfa administered prior to the switch to Mircera, and was either 120, 200 or 360 µg Mircera per month. The dose was then adjusted to maintain Hemoglobin levels within the defined target range and also according to the need for red blood cell transfusions (due to worsening anemia), or for toxicity related to Mircera.	Darbepoetin Alfa Participants continued to receive the same dose of darbepoetin alfa by subcutaneous injection once every week, once every 2 weeks or once every month as per local labeling during the dose titration (7 months) and the evaluation period (2 months).
Titration Period Adverse Event	2	0
Titration Period Death	3	2
Titration Period Insufficient Therapeutic Response	1	0
Titration Period Refused Treatment	4	1
Titration Period Failure to return	1	0
Titration Period Hospitalized in another hospital	1	0
Evaluation Period Adverse Event	1	0
Evaluation Period Death	1	1
Evaluation Period Insufficient Therapeutic Response	1	0
Evaluation Period Refused treatment	1	1
Evaluation Period Renal transplant	0	1
Evaluation Period Failure to return	1	0
Evaluation Period Site closure	0	1

Baseline Characteristics

A Study of Subcutaneous Mircera in Patients With Chronic Kidney Disease, Not on Dialysis.

Baseline characteristics by cohort

Measure	Mircera n=114 Participants Participants received Mircera by subcutaneous injection once every month during the dose titration (7 months) and evaluation period (2 months). The starting dose was based on the weekly dose of darbepoetin alfa administered prior to the switch to Mircera, and was either 120, 200 or 360 µg Mircera per month. The dose was then adjusted to maintain Hemoglobin levels within the defined target range and also according to the need for red blood cell transfusions (due to worsening anemia), or for toxicity related to Mircera.	Darbepoetin Alfa n=114 Participants Participants continued to receive the same dose of darbepoetin alfa by subcutaneous injection once every week, once every 2 weeks or once every month as per local labeling during the dose titration (7 months) and the evaluation period (2 months).	Total n=228 Participants Total of all reporting groups
Age Continuous	71.3 years STANDARD_DEVIATION 11.03 • n=5 Participants	69.6 years STANDARD_DEVIATION 14.02 • n=7 Participants	70.4 years STANDARD_DEVIATION 12.62 • n=5 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	66 Participants n=7 Participants	132 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	48 Participants n=7 Participants	96 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (measurements at Week -4, Week -2 and Day 1) and Evaluation Period (Months 8 and 9; measurements twice a month and at the final visit).

Population: Per Protocol population consisted of all randomized patients who had received at least one dose of trial medication and who have no major protocol violation. Data missing at the end of the evaluation period were handled using the last observation carried forward method (LOCF).

A time adjusted average baseline hemoglobin (Hb) concentration was calculated using the trapezoid rule from all available Hb measurements taken during the baseline period. The average evaluation period Hb concentration for each individual was calculated using the same method, from all their available measurements taken during the two month evaluation period. The change in Hb concentration between the baseline and evaluation periods was calculated by subtracting the baseline Hb from the evaluation period Hb. All blood samples for Hb measurements were taken prior to study drug administration.

Outcome measures

Measure	Mircera n=91 Participants Participants received Mircera by subcutaneous injection once every month during the dose titration (7 months) and evaluation period (2 months). The starting dose was based on the weekly dose of darbepoetin alfa administered prior to the switch to Mircera, and was either 120, 200 or 360 µg Mircera per month. The dose was then adjusted to maintain Hemoglobin levels within the defined target range and also according to the need for red blood cell transfusions (due to worsening anemia), or for toxicity related to Mircera.	Darbepoetin Alfa n=99 Participants Participants continued to receive the same dose of darbepoetin alfa by subcutaneous injection once every week, once every 2 weeks or once every month as per local labeling during the dose titration (7 months) and the evaluation period (2 months).
Change in Hemoglobin (Hb) Concentration From Baseline to the Evaluation Period Baseline Hb	11.29 g/dL Standard Deviation 0.382	11.33 g/dL Standard Deviation 0.397
Change in Hemoglobin (Hb) Concentration From Baseline to the Evaluation Period Change from baseline	0.15 g/dL Standard Deviation 0.899	-0.03 g/dL Standard Deviation 0.693

SECONDARY outcome

Timeframe: From Baseline to 9 months; blood samples for hemoglobin measurements were taken twice a month, at each study visit.

Population: Intent-to-treat population, including all randomized patients. "n" refers to the number of patients for whom data was available at each time point.

Outcome measures

Measure	Mircera n=114 Participants Participants received Mircera by subcutaneous injection once every month during the dose titration (7 months) and evaluation period (2 months). The starting dose was based on the weekly dose of darbepoetin alfa administered prior to the switch to Mircera, and was either 120, 200 or 360 µg Mircera per month. The dose was then adjusted to maintain Hemoglobin levels within the defined target range and also according to the need for red blood cell transfusions (due to worsening anemia), or for toxicity related to Mircera.	Darbepoetin Alfa n=114 Participants Participants continued to receive the same dose of darbepoetin alfa by subcutaneous injection once every week, once every 2 weeks or once every month as per local labeling during the dose titration (7 months) and the evaluation period (2 months).
Change in Hemoglobin Concentration From Baseline Over Time Change at 6.5 Months [n=100, 110]	0.06 g/dL Standard Deviation 1.087	0.04 g/dL Standard Deviation 0.817
Change in Hemoglobin Concentration From Baseline Over Time Change at 7 Months [n=102, 111]	0.03 g/dL Standard Deviation 1.008	-0.00 g/dL Standard Deviation 0.842
Change in Hemoglobin Concentration From Baseline Over Time Change at 7.5 Months [n=99, 110]	0.12 g/dL Standard Deviation 1.166	-0.00 g/dL Standard Deviation 0.873
Change in Hemoglobin Concentration From Baseline Over Time Baseline [n=114, 114]	11.27 g/dL Standard Deviation 0.390	11.31 g/dL Standard Deviation 0.393
Change in Hemoglobin Concentration From Baseline Over Time Change at 0.5 Months [n=113, 114]	0.29 g/dL Standard Deviation 0.737	0.03 g/dL Standard Deviation 0.490
Change in Hemoglobin Concentration From Baseline Over Time Change at 1 Month [n=114, 113]	0.34 g/dL Standard Deviation 0.813	0.06 g/dL Standard Deviation 0.575
Change in Hemoglobin Concentration From Baseline Over Time Change at 1.5 Months [n=111, 113]	0.45 g/dL Standard Deviation 0.866	0.11 g/dL Standard Deviation 0.599
Change in Hemoglobin Concentration From Baseline Over Time Change at 2 Months [n=112, 112]	0.27 g/dL Standard Deviation 0.897	0.02 g/dL Standard Deviation 0.716
Change in Hemoglobin Concentration From Baseline Over Time Change at 2.5 Months [n=110, 112]	0.45 g/dL Standard Deviation 0.924	0.16 g/dL Standard Deviation 0.673
Change in Hemoglobin Concentration From Baseline Over Time Change at 3 Months [n=111, 112]	0.23 g/dL Standard Deviation 1.010	0.10 g/dL Standard Deviation 0.602
Change in Hemoglobin Concentration From Baseline Over Time Change at 3.5 Months [n=108, 108]	0.18 g/dL Standard Deviation 1.095	0.05 g/dL Standard Deviation 0.675
Change in Hemoglobin Concentration From Baseline Over Time Change at 4 Months [n=109, 110]	0.05 g/dL Standard Deviation 0.893	0.00 g/dL Standard Deviation 0.681
Change in Hemoglobin Concentration From Baseline Over Time Change at 4.5 Months [n=104, 108]	0.18 g/dL Standard Deviation 0.940	0.13 g/dL Standard Deviation 0.699
Change in Hemoglobin Concentration From Baseline Over Time Change at 5 Months [n=108, 111]	-0.03 g/dL Standard Deviation 0.897	-0.07 g/dL Standard Deviation 0.757
Change in Hemoglobin Concentration From Baseline Over Time Change at 5.5 Months [n=105, 110]	0.15 g/dL Standard Deviation 0.922	-0.03 g/dL Standard Deviation 0.729
Change in Hemoglobin Concentration From Baseline Over Time Change at 6 Months [n=103, 111]	-0.05 g/dL Standard Deviation 0.988	-0.06 g/dL Standard Deviation 0.820
Change in Hemoglobin Concentration From Baseline Over Time Change at 8 Months [n=100, 108]	-0.04 g/dL Standard Deviation 1.198	-0.12 g/dL Standard Deviation 0.905
Change in Hemoglobin Concentration From Baseline Over Time Change at 8.5 Months [n=97, 107]	0.14 g/dL Standard Deviation 1.256	0.02 g/dL Standard Deviation 0.766
Change in Hemoglobin Concentration From Baseline Over Time Change at 9 Months [n=94, 101]	0.07 g/dL Standard Deviation 1.045	-0.06 g/dL Standard Deviation 0.956

SECONDARY outcome

Timeframe: From randomization to Month 9

Population: Safety population included all randomized patients who received at least one dose of trial medication and a safety follow-up, according to the treatment received.

Red blood cell (RBC) transfusions could be given during the treatment period in case of medical need, i.e., in severely anemic patients with recognized symptoms or signs of anemia (e.g., in patients with acute blood loss, with severe angina, or whose Hemoglobin decreased to critical levels). The number of participants who had at least one red blood cell transfusion during the entire study, during the Titration Period and during the Evaluation Period is presented. Participants who received more than one transfusion within a defined period are only counted once.

Outcome measures

Measure	Mircera n=115 Participants Participants received Mircera by subcutaneous injection once every month during the dose titration (7 months) and evaluation period (2 months). The starting dose was based on the weekly dose of darbepoetin alfa administered prior to the switch to Mircera, and was either 120, 200 or 360 µg Mircera per month. The dose was then adjusted to maintain Hemoglobin levels within the defined target range and also according to the need for red blood cell transfusions (due to worsening anemia), or for toxicity related to Mircera.	Darbepoetin Alfa n=113 Participants Participants continued to receive the same dose of darbepoetin alfa by subcutaneous injection once every week, once every 2 weeks or once every month as per local labeling during the dose titration (7 months) and the evaluation period (2 months).
Number of Participants With Red Blood Cell (RBC) Transfusions Entire Study	9 participants	3 participants
Number of Participants With Red Blood Cell (RBC) Transfusions Titration Period	5 participants	1 participants
Number of Participants With Red Blood Cell (RBC) Transfusions Evaluation Period	5 participants	2 participants

SECONDARY outcome

Timeframe: Randomization to Month 10 (final visit)

Population: Safety population

Adverse events were collected during the treatment period (from the first treatment dose) up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period.

Outcome measures

Measure	Mircera n=115 Participants Participants received Mircera by subcutaneous injection once every month during the dose titration (7 months) and evaluation period (2 months). The starting dose was based on the weekly dose of darbepoetin alfa administered prior to the switch to Mircera, and was either 120, 200 or 360 µg Mircera per month. The dose was then adjusted to maintain Hemoglobin levels within the defined target range and also according to the need for red blood cell transfusions (due to worsening anemia), or for toxicity related to Mircera.	Darbepoetin Alfa n=113 Participants Participants continued to receive the same dose of darbepoetin alfa by subcutaneous injection once every week, once every 2 weeks or once every month as per local labeling during the dose titration (7 months) and the evaluation period (2 months).
Participants With Adverse Events Any adverse event	102 participants	88 participants
Participants With Adverse Events Fatal Adverse event	4 participants	3 participants
Participants With Adverse Events Serious adverse event	41 participants	23 participants
Participants With Adverse Events Adverse event leading to withdrawal	3 participants	0 participants

Adverse Events

Mircera

Serious events: 41 serious events

Other events: 59 other events

Deaths: 0 deaths

Darbepoetin Alfa

Serious events: 23 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Measure	Mircera n=115 participants at risk Participants received Mircera by subcutaneous injection once every month during the dose titration (7 months) and evaluation period (2 months). The starting dose was based on the weekly dose of darbepoetin alfa administered prior to the switch to Mircera, and was either 120, 200 or 360 µg Mircera per month. The dose was then adjusted to maintain Hemoglobin levels within the defined target range and also according to the need for red blood cell transfusions (due to worsening anemia), or for toxicity related to Mircera.	Darbepoetin Alfa n=113 participants at risk Participants continued to receive the same dose of darbepoetin alfa by subcutaneous injection once every week, once every 2 weeks or once every month as per local labeling during the dose titration (7 months) and the evaluation period (2 months).
Cardiac disorders SICK SINUS SYNDROME	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders CARDIAC FAILURE CONGESTIVE	1.7% 2/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders ATRIAL FIBRILLATION	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders AORTIC VALVE DISEASE MIXED	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders ARRHYTHMIA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders ATRIAL FLUTTER	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders BRADYCARDIA	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders CARDIAC FAILURE	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders CARDIOGENIC SHOCK	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders CORONARY ARTERY DISEASE	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders MYOCARDIAL INFARCTION	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders MYOCARDIAL ISCHAEMIA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Cardiac disorders SILENT MYOCARDIAL INFARCTION	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Infections and infestations PNEUMONIA	1.7% 2/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Infections and infestations RESPIRATORY TRACT INFECTION	1.7% 2/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Infections and infestations BRONCHOPNEUMONIA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Infections and infestations CORYNEBACTERIUM SEPSIS	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Infections and infestations GASTROENTERITIS	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Infections and infestations INFECTED SKIN ULCER	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Infections and infestations NEUROLOGICAL INFECTION	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Infections and infestations OSTEOMYELITIS	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Infections and infestations POST PROCEDURAL INFECTION	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Infections and infestations URINARY TRACT INFECTION	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Metabolism and nutrition disorders FLUID OVERLOAD	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Metabolism and nutrition disorders HYPERKALAEMIA	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	1.8% 2/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Metabolism and nutrition disorders DEHYDRATION	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Metabolism and nutrition disorders DIABETES MELLITUS INADEQUATE CONTROL	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Metabolism and nutrition disorders FLUID RETENTION	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Metabolism and nutrition disorders HYPOGLYCAEMIA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Metabolism and nutrition disorders HYPONATRAEMIA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Nervous system disorders CEREBROVASCULAR ACCIDENT	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Nervous system disorders ATAXIA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Nervous system disorders HEADACHE	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Nervous system disorders NERVE ROOT COMPRESSION	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Nervous system disorders PARTIAL SEIZURES	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Nervous system disorders SCIATICA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Nervous system disorders TRANSIENT ISCHAEMIC ATTACK	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Nervous system disorders VERTEBROBASILAR INSUFFICIENCY	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Renal and urinary disorders RENAL IMPAIRMENT	4.3% 5/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Renal and urinary disorders RENAL FAILURE CHRONIC	1.7% 2/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Renal and urinary disorders CALCULUS URETERIC	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Gastrointestinal disorders PANCREATITIS ACUTE	1.7% 2/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Gastrointestinal disorders COLITIS ISCHAEMIC	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Gastrointestinal disorders DIARRHOEA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Gastrointestinal disorders HIATUS HERNIA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Gastrointestinal disorders RECTAL POLYP	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Injury, poisoning and procedural complications LOWER LIMB FRACTURE	1.7% 2/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Injury, poisoning and procedural complications FEMORAL NECK FRACTURE	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Injury, poisoning and procedural complications PELVIC FRACTURE	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Ear and labyrinth disorders VERTIGO	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	1.8% 2/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ANGIOSARCOMA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BASAL CELL CARCINOMA	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) COLON CANCER METASTATIC	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Vascular disorders ARTERIOSCLEROSIS	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Vascular disorders EXTREMITY NECROSIS	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Vascular disorders HYPERTENSION	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
General disorders NON-CARDIAC CHEST PAIN	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
General disorders OEDEMA PERIPHERAL	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Hepatobiliary disorders CHOLECYSTITIS	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Hepatobiliary disorders CHOLELITHIASIS	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Musculoskeletal and connective tissue disorders PATHOLOGICAL FRACTURE	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Respiratory, thoracic and mediastinal disorders ASTHMA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Respiratory, thoracic and mediastinal disorders CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Skin and subcutaneous tissue disorders SKIN ULCER	1.7% 2/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Blood and lymphatic system disorders NEPHROGENIC ANAEMIA	0.87% 1/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.00% 0/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Eye disorders CATARACT	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Reproductive system and breast disorders BENIGN PROSTATIC HYPERPLASIA	0.00% 0/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.

Other adverse events

Measure	Mircera n=115 participants at risk Participants received Mircera by subcutaneous injection once every month during the dose titration (7 months) and evaluation period (2 months). The starting dose was based on the weekly dose of darbepoetin alfa administered prior to the switch to Mircera, and was either 120, 200 or 360 µg Mircera per month. The dose was then adjusted to maintain Hemoglobin levels within the defined target range and also according to the need for red blood cell transfusions (due to worsening anemia), or for toxicity related to Mircera.	Darbepoetin Alfa n=113 participants at risk Participants continued to receive the same dose of darbepoetin alfa by subcutaneous injection once every week, once every 2 weeks or once every month as per local labeling during the dose titration (7 months) and the evaluation period (2 months).
Vascular disorders HYPERTENSION	26.1% 30/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	17.7% 20/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Infections and infestations NASOPHARYNGITIS	6.1% 7/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	11.5% 13/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Infections and infestations URINARY TRACT INFECTION	8.7% 10/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	3.5% 4/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Renal and urinary disorders RENAL IMPAIRMENT	11.3% 13/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	10.6% 12/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Gastrointestinal disorders DIARRHOEA	4.3% 5/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	7.1% 8/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Gastrointestinal disorders CONSTIPATION	5.2% 6/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	2.7% 3/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
General disorders OEDEMA DUE TO RENAL DISEASE	5.2% 6/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	6.2% 7/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Endocrine disorders HYPERPARATHYROIDISM SECONDARY	7.0% 8/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	0.88% 1/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.
Musculoskeletal and connective tissue disorders BACK PAIN	5.2% 6/115 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.	2.7% 3/113 • All adverse events that occurred from the first treatment dose were summarized. Adverse events were included up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. Safety population was used for analysis.

Additional Information

Medical Communications

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• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER