Trial Outcomes & Findings for Evaluation of Monthly Darbepoetin Alfa Dosing for Correction of Anemia in Non-dialysis Chronic Kidney Disease (NCT NCT00925587)

NCT ID: NCT00925587

Last Updated: 2014-06-04

Results Overview

The Adjusted Analysis is the primary analysis and includes treatment group and baseline Hb value as covariates. Non-inferiority is concluded if the lower limit of the 95% confidence interval for the mean difference is above -0.5g/dL.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 358 participants
• Primary outcome timeframe: Baseline Week 33
• Results posted on: 2014-06-04

Participant Flow

Participant milestones

Measure	Darbepoetin Alfa Q2W Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM Darbepoetin alfa Intravenous Once Monthly
Overall Study STARTED	178	180
Overall Study COMPLETED	142	155
Overall Study NOT COMPLETED	36	25

Reasons for withdrawal

Measure	Darbepoetin Alfa Q2W Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM Darbepoetin alfa Intravenous Once Monthly
Overall Study Protocol Specified Criteria	6	6
Overall Study Physician Decision	4	1
Overall Study Protocol Violation	6	4
Overall Study Withdrawal by Subject	9	6
Overall Study Death	5	5
Overall Study Adverse Event	6	2
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Evaluation of Monthly Darbepoetin Alfa Dosing for Correction of Anemia in Non-dialysis Chronic Kidney Disease

Baseline characteristics by cohort

Measure	Darbepoetin Alfa Q2W n=175 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=180 Participants Darbepoetin alfa Intravenous Once Monthly	Total n=355 Participants Total of all reporting groups
Age, Continuous	68.4 years STANDARD_DEVIATION 14.1 • n=5 Participants	66.3 years STANDARD_DEVIATION 15.2 • n=7 Participants	67.3 years STANDARD_DEVIATION 14.7 • n=5 Participants
Age, Customized <65 years	60 Participants n=5 Participants	67 Participants n=7 Participants	127 Participants n=5 Participants
Age, Customized >=65-<75 years	42 Participants n=5 Participants	54 Participants n=7 Participants	96 Participants n=5 Participants
Age, Customized >=75 years	73 Participants n=5 Participants	59 Participants n=7 Participants	132 Participants n=5 Participants
Sex: Female, Male Female	107 Participants n=5 Participants	104 Participants n=7 Participants	211 Participants n=5 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	76 Participants n=7 Participants	144 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	166 Participants n=5 Participants	163 Participants n=7 Participants	329 Participants n=5 Participants
Race/Ethnicity, Customized Other	9 Participants n=5 Participants	16 Participants n=7 Participants	25 Participants n=5 Participants
Baseline Hemoglobin	9.13 g/dL STANDARD_DEVIATION 0.61 • n=5 Participants	9.11 g/dL STANDARD_DEVIATION 0.70 • n=7 Participants	9.12 g/dL STANDARD_DEVIATION 0.65 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline Week 33

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

The Adjusted Analysis is the primary analysis and includes treatment group and baseline Hb value as covariates. Non-inferiority is concluded if the lower limit of the 95% confidence interval for the mean difference is above -0.5g/dL.

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Hb Change Between Baseline and the Evaluation Period (Average of Weeks 29-33)	2.157 g/dL Interval 1.984 to 2.33	1.969 g/dL Interval 1.803 to 2.135

SECONDARY outcome

Timeframe: Baseline to Week 33

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Achievement of Both a Hb >= 10.0 g/dL and a >= 1.0 g/dL Increase From Baseline at Any Time Point Following de Novo Darbepoetin Alfa Administration.	97.9 Percentage of Participants Interval 95.5 to 100.0	98.1 Percentage of Participants Interval 95.9 to 100.0

SECONDARY outcome

Timeframe: Baseline

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Baseline	9.17 g/dL Standard Error 0.05	9.12 g/dL Standard Error 0.06

SECONDARY outcome

Timeframe: Week 3

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=141 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 3	9.89 g/dL Standard Error 0.08	10.13 g/dL Standard Error 0.10

SECONDARY outcome

Timeframe: Week 5

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=152 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 5	10.58 g/dL Standard Error 0.08	10.28 g/dL Standard Error 0.09

SECONDARY outcome

Timeframe: Week 7

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=140 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=152 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 7	10.90 g/dL Standard Error 0.09	10.75 g/dL Standard Error 0.10

SECONDARY outcome

Timeframe: Week 9

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=140 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 9	11.24 g/dL Standard Error 0.10	10.79 g/dL Standard Error 0.10

SECONDARY outcome

Timeframe: Week 11

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=139 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=151 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 11	11.35 g/dL Standard Error 0.10	11.17 g/dL Standard Error 0.10

SECONDARY outcome

Timeframe: Week 13

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=140 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=149 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 13	11.56 g/dL Standard Error 0.10	11.05 g/dL Standard Error 0.10

SECONDARY outcome

Timeframe: Week 15

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=139 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=150 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 15	11.42 g/dL Standard Error 0.11	11.25 g/dL Standard Error 0.09

SECONDARY outcome

Timeframe: Week 17

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=138 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=150 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 17	11.66 g/dL Standard Error 0.10	11.12 g/dL Standard Error 0.09

SECONDARY outcome

Timeframe: Week 19

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=139 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=148 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 19	11.50 g/dL Standard Error 0.12	11.20 g/dL Standard Error 0.09

SECONDARY outcome

Timeframe: Week 21

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=137 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=146 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 21	11.53 g/dL Standard Error 0.10	11.09 g/dL Standard Error 0.08

SECONDARY outcome

Timeframe: Week 23

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=138 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=148 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 23	11.36 g/dL Standard Error 0.09	11.08 g/dL Standard Error 0.09

SECONDARY outcome

Timeframe: Week 25

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=139 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=151 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 25	11.34 g/dL Standard Error 0.10	10.85 g/dL Standard Error 0.09

SECONDARY outcome

Timeframe: Week 27

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=138 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=150 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 27	11.22 g/dL Standard Error 0.09	11.07 g/dL Standard Error 0.09

SECONDARY outcome

Timeframe: Week 29

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=137 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=151 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 29	11.35 g/dL Standard Error 0.10	10.90 g/dL Standard Error 0.09

SECONDARY outcome

Timeframe: Week 31

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=140 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=152 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 31	11.31 g/dL Standard Error 0.09	11.28 g/dL Standard Error 0.09

SECONDARY outcome

Timeframe: Week 33

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=136 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=149 Participants Darbepoetin alfa Intravenous Once Monthly
Hb at Week 33	11.38 g/dL Standard Error 0.10	11.15 g/dL Standard Error 0.10

SECONDARY outcome

Timeframe: Week 1

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 1	27.65 µg/wk 95% Confidence Interval 0.10 • Interval 26.59 to 28.76	27.06 µg/wk 95% Confidence Interval 0.10 • Interval 26.09 to 28.06

SECONDARY outcome

Timeframe: Week 3

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=141 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 3	25.80 µg/wk 95% Confidence Interval 0.10 • Interval 24.64 to 27.0	27.06 µg/wk 95% Confidence Interval 0.10 • Interval 26.09 to 28.06

SECONDARY outcome

Timeframe: Week 5

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 5	24.40 µg/wk 95% Confidence Interval 0.10 • Interval 22.7 to 26.23	24.52 µg/wk 95% Confidence Interval 0.10 • Interval 22.7 to 26.5

SECONDARY outcome

Timeframe: Week 7

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=141 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 7	23.42 µg/wk 95% Confidence Interval 0.10 • Interval 21.42 to 25.61	24.52 µg/wk 95% Confidence Interval 0.10 • Interval 22.7 to 26.5

SECONDARY outcome

Timeframe: Week 9

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=141 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 9	20.01 µg/wk 95% Confidence Interval 0.10 • Interval 17.36 to 23.07	20.59 µg/wk 95% Confidence Interval 0.10 • Interval 17.89 to 23.7

SECONDARY outcome

Timeframe: Week 11

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=139 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 11	18.99 µg/wk 95% Confidence Interval 0.10 • Interval 16.22 to 22.24	20.50 µg/wk 95% Confidence Interval 0.10 • Interval 17.83 to 23.58

SECONDARY outcome

Timeframe: Week 13

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=151 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 13	14.67 µg/wk 95% Confidence Interval 0.10 • Interval 11.97 to 17.98	19.52 µg/wk 95% Confidence Interval 0.10 • Interval 16.79 to 22.69

SECONDARY outcome

Timeframe: Week 15

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=141 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 15	14.19 µg/wk 95% Confidence Interval 0.10 • Interval 11.52 to 17.47	19.15 µg/wk 95% Confidence Interval 0.10 • Interval 16.42 to 22.33

SECONDARY outcome

Timeframe: Week 17

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=140 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 17	12.71 µg/wk 95% Confidence Interval 0.10 • Interval 10.15 to 15.92	19.94 µg/wk 95% Confidence Interval 0.10 • Interval 17.28 to 23.02

SECONDARY outcome

Timeframe: Week 19

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 19	14.52 µg/wk 95% Confidence Interval 0.10 • Interval 11.97 to 17.61	19.94 µg/wk 95% Confidence Interval 0.10 • Interval 17.28 to 23.01

SECONDARY outcome

Timeframe: Week 21

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=140 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=150 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 21	15.42 µg/wk 95% Confidence Interval 0.10 • Interval 12.96 to 18.36	21.59 µg/wk 95% Confidence Interval 0.10 • Interval 19.2 to 24.29

SECONDARY outcome

Timeframe: Week 23

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=141 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 23	14.73 µg/wk 95% Confidence Interval 0.10 • Interval 12.35 to 17.57	19.98 µg/wk 95% Confidence Interval 0.10 • Interval 17.39 to 22.94

SECONDARY outcome

Timeframe: Week 25

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 25	14.55 µg/wk 95% Confidence Interval 0.10 • Interval 12.16 to 17.41	20.70 µg/wk 95% Confidence Interval 0.10 • Interval 18.1 to 23.68

SECONDARY outcome

Timeframe: Week 27

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=139 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 27	16.07 µg/wk 95% Confidence Interval 0.10 • Interval 13.69 to 18.85	20.79 µg/wk 95% Confidence Interval 0.10 • Interval 18.18 to 23.77

SECONDARY outcome

Timeframe: Week 29

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=137 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=151 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 29	15.06 µg/wk 95% Confidence Interval 0.10 • Interval 12.75 to 17.78	20.57 µg/wk 95% Confidence Interval 0.10 • Interval 17.74 to 23.85

SECONDARY outcome

Timeframe: Week 31

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=139 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose at Week 31	14.48 µg/wk 95% Confidence Interval 0.10 • Interval 12.2 to 17.19	19.39 µg/wk 95% Confidence Interval 0.10 • Interval 16.51 to 22.77

SECONDARY outcome

Timeframe: Weeks 29-33

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=140 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Darbepoetin Alfa Dose During the Evaluation Period (Average of Weeks 29-33)	15.21 µg/wk 95% Confidence Interval 0.10 • Interval 12.99 to 17.81	19.68 µg/wk 95% Confidence Interval 0.10 • Interval 16.84 to 23.01

SECONDARY outcome

Timeframe: Week 3

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=141 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 3	0.931 ratio 95% Confidence Interval 0.10 • Interval 0.914 to 0.947	1.000 ratio 95% Confidence Interval 0.10 • Interval 1.0 to 1.0

SECONDARY outcome

Timeframe: Week 5

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 5	0.882 ratio 95% Confidence Interval 0.10 • Interval 0.832 to 0.936	0.907 ratio 95% Confidence Interval 0.10 • Interval 0.845 to 0.974

SECONDARY outcome

Timeframe: Week 7

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=141 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 7	0.845 ratio 95% Confidence Interval 0.10 • Interval 0.782 to 0.914	0.907 ratio 95% Confidence Interval 0.10 • Interval 0.845 to 0.974

SECONDARY outcome

Timeframe: Week 9

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=141 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 9	0.724 ratio 95% Confidence Interval 0.10 • Interval 0.631 to 0.832	0.761 ratio 95% Confidence Interval 0.10 • Interval 0.662 to 0.875

SECONDARY outcome

Timeframe: Week 11

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=139 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 11	0.684 ratio 95% Confidence Interval 0.10 • Interval 0.588 to 0.797	0.758 ratio 95% Confidence Interval 0.10 • Interval 0.659 to 0.871

SECONDARY outcome

Timeframe: Week 13

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=151 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 13	0.531 ratio 95% Confidence Interval 0.10 • Interval 0.435 to 0.647	0.719 ratio 95% Confidence Interval 0.10 • Interval 0.62 to 0.835

SECONDARY outcome

Timeframe: Week 15

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=141 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 15	0.512 ratio 95% Confidence Interval 0.10 • Interval 0.417 to 0.628	0.707 ratio 95% Confidence Interval 0.10 • Interval 0.608 to 0.823

SECONDARY outcome

Timeframe: Week 17

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=140 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 17	0.459 ratio 95% Confidence Interval 0.10 • Interval 0.368 to 0.572	0.737 ratio 95% Confidence Interval 0.10 • Interval 0.641 to 0.847

SECONDARY outcome

Timeframe: Week 19

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 19	0.525 ratio 95% Confidence Interval 0.10 • Interval 0.435 to 0.633	0.737 ratio 95% Confidence Interval 0.10 • Interval 0.641 to 0.846

SECONDARY outcome

Timeframe: Week 21

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=140 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=150 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 21	0.556 ratio 95% Confidence Interval 0.10 • Interval 0.471 to 0.656	0.797 ratio 95% Confidence Interval 0.10 • Interval 0.713 to 0.891

SECONDARY outcome

Timeframe: Week 23

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=141 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 23	0.533 ratio 95% Confidence Interval 0.10 • Interval 0.45 to 0.632	0.738 ratio 95% Confidence Interval 0.10 • Interval 0.646 to 0.844

SECONDARY outcome

Timeframe: Week 25

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 25	0.526 ratio 95% Confidence Interval 0.10 • Interval 0.443 to 0.625	0.764 ratio 95% Confidence Interval 0.10 • Interval 0.671 to 0.869

SECONDARY outcome

Timeframe: Week 27

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=139 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 27	0.581 ratio 95% Confidence Interval 0.10 • Interval 0.499 to 0.677	0.768 ratio 95% Confidence Interval 0.10 • Interval 0.675 to 0.875

SECONDARY outcome

Timeframe: Week 29

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=137 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=151 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 29	0.544 ratio 95% Confidence Interval 0.10 • Interval 0.462 to 0.64	0.762 ratio 95% Confidence Interval 0.10 • Interval 0.661 to 0.88

SECONDARY outcome

Timeframe: Week 31

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=139 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at Week 31	0.525 ratio 95% Confidence Interval 0.10 • Interval 0.443 to 0.622	0.717 ratio 95% Confidence Interval 0.10 • Interval 0.613 to 0.839

SECONDARY outcome

Timeframe: Weeks 1-33

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=139 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=151 Participants Darbepoetin alfa Intravenous Once Monthly
Dose of Darbepoetin Alfa at the First Achievement of a Hb ≥10.0 g/dL and a ≥1.0 g/dL Increase From Baseline (Weeks 1-33)	25.95 µg/wk 95% Confidence Interval 0.10 • Interval 24.43 to 27.56	29.65 µg/wk 95% Confidence Interval 0.10 • Interval 27.89 to 31.52

SECONDARY outcome

Timeframe: Weeks 1-33

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Outcome measures

Measure	Darbepoetin Alfa Q2W n=142 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=154 Participants Darbepoetin alfa Intravenous Once Monthly
Time to First Achievement of a Hb ≥10.0 g/dL and a ≥1.0 g/dL Increase From Baseline (Weeks 1-33)	5.0 Weeks Interval 3.0 to 7.0	5.0 Weeks Interval 3.0 to 9.0

SECONDARY outcome

Timeframe: Evaluation Period

Population: Primary Analysis Set: All subjects receiving at least one dose of darbepoetin alfa in the treatment group to which they were randomized and with at least one evaluable (not within 90 days after an RBC transfusion) Hb measurement during the evaluation period (Weeks 29-33)

Although the endpoint is related to dose, the sample is from the Primary Analysis Set which requires a Hb value in the evaluation period

Outcome measures

Measure	Darbepoetin Alfa Q2W n=140 Participants Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=153 Participants Darbepoetin alfa Intravenous Once Monthly
Ratio of Darbepoetin Alfa Dose to Baseline at the Evalaution Period (Average of Weeks 29-33)	0.550 ratio 95% Confidence Interval 0.10 • Interval 0.471 to 0.643	0.728 ratio 95% Confidence Interval 0.10 • Interval 0.625 to 0.849

Adverse Events

Darbepoetin Alfa Q2W

Serious events: 52 serious events

Other events: 68 other events

Deaths: 0 deaths

Darbepoetin Alfa QM

Serious events: 54 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Measure	Darbepoetin Alfa Q2W n=175 participants at risk Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=180 participants at risk Darbepoetin alfa Intravenous Once Monthly
Blood and lymphatic system disorders Anaemia	1.1% 2/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.8% 5/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Acute coronary syndrome	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Acute myocardial infarction	1.1% 2/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Angina pectoris	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Arrhythmia	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Arrhythmia supraventricular	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Atrial fibrillation	1.1% 2/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Atrial flutter	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Atrioventricular block complete	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Cardiac failure	3.4% 6/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.7% 3/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Cardiac failure acute	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Cardiac failure congestive	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Coronary artery disease	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Ischaemic cardiomyopathy	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Myocardial ischaemia	1.1% 2/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Tachyarrhythmia	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Cardiac disorders Ventricular tachycardia	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Ear and labyrinth disorders Vertigo	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Eye disorders Cataract	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Eye disorders Retinal haemorrhage	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Eye disorders Visual impairment	1.1% 2/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Abdominal pain	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Acute abdomen	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Alcoholic pancreatitis	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Diaphragmatic hernia	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Diarrhoea	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Dyspepsia	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Ileus	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.7% 3/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Impaired gastric emptying	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Melaena	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Asthenia	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Chest pain	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Generalised oedema	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Inflammation	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Oedema peripheral	1.1% 2/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Spinal pain	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Hepatobiliary disorders Biliary colic	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Hepatobiliary disorders Cholecystitis	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Immune system disorders Anti-neutrophil cytoplasmic antibody positive vasculitis	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Abdominal abscess	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Appendicitis	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Bronchitis	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Bronchopneumonia	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Erysipelas	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Gangrene	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Gastroenteritis	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Gastroenteritis viral	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Infection	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Lobar pneumonia	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Parainfluenzae virus infection	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Peritonitis	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Pneumonia	1.7% 3/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Pyelonephritis chronic	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Sepsis	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Urinary tract infection	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Injury, poisoning and procedural complications Concussion	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Injury, poisoning and procedural complications Fall	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Injury, poisoning and procedural complications Femoral neck fracture	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Injury, poisoning and procedural complications Femur fracture	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Injury, poisoning and procedural complications Pelvic fracture	1.1% 2/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Injury, poisoning and procedural complications Radius fracture	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Injury, poisoning and procedural complications Skull fractured base	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Injury, poisoning and procedural complications Wrist fracture	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Investigations Blood glucose increased	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Investigations Blood potassium increased	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Investigations General physical condition abnormal	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Investigations International normalised ratio increased	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Dehydration	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Diabetes mellitus	1.7% 3/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Fluid overload	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Carotid artery stenosis	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Cerebral ischaemia	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Cerebrovascular accident	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Convulsion	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Hemiparesis	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Hypoaesthesia	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Ischaemic stroke	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Loss of consciousness	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Syncope	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Transient ischaemic attack	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Vascular encephalopathy	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Psychiatric disorders Depression	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Renal and urinary disorders Azotaemia	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Renal and urinary disorders Diabetic nephropathy	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Renal and urinary disorders Nephropathy	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Renal and urinary disorders Renal failure	2.3% 4/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Renal and urinary disorders Renal failure acute	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.2% 4/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Renal and urinary disorders Renal failure chronic	4.0% 7/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.2% 4/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Reproductive system and breast disorders Epididymitis	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Reproductive system and breast disorders Oedema genital	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Reproductive system and breast disorders Scrotal swelling	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.1% 2/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Skin and subcutaneous tissue disorders Dry gangrene	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Vascular disorders Aortic aneurysm	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Vascular disorders Circulatory collapse	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Vascular disorders Extremity necrosis	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Vascular disorders Haematoma	0.57% 1/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Vascular disorders Hypertension	1.7% 3/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.1% 2/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Vascular disorders Hypertensive crisis	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Vascular disorders Orthostatic hypotension	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Vascular disorders Peripheral ischaemia	0.00% 0/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.56% 1/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.

Other adverse events

Measure	Darbepoetin Alfa Q2W n=175 participants at risk Darbepoetin alfa Intravenous Once Every 2 Weeks	Darbepoetin Alfa QM n=180 participants at risk Darbepoetin alfa Intravenous Once Monthly
Gastrointestinal disorders Diarrhoea	5.7% 10/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.9% 7/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Asthenia	5.7% 10/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.8% 5/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Oedema peripheral	9.7% 17/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	7.8% 14/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Urinary tract infection	4.6% 8/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	5.6% 10/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hyperkalaemia	4.0% 7/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	6.7% 12/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Vascular disorders Hypertension	20.6% 36/175 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	16.7% 30/180 • 33 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results aftercompletion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER