Trial Outcomes & Findings for Compare Efficacy/Safety of Repeat Doses of Ferumoxytol With Iron Sucrose in CKD Subjects With IDA and on Hemodialysis (NCT NCT01227616)

NCT ID: NCT01227616

Last Updated: 2022-04-21

Results Overview

Changes in the mean hemoglobin between Baseline and Week 5 for ferumoxytol and iron sucrose in each treatment period.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

296 participants

Primary outcome timeframe

Up to 6 treatment periods (5 weeks per treatment period)

Results posted on

2022-04-21

Participant Flow

A total of 296 hemodialysis patients with IDA who met the entry criteria were enrolled and randomized (ferumoxytol: n=197; iron sucrose: n=99). One subject in the ferumoxytol group and 2 subjects in the iron sucrose group withdrew prior to receiving study drug, resulting in 293 total participants for analysis.

Participant milestones

Participant milestones
Measure	Ferumoxytol 30 mg Fe/mL for IV injection	Iron Sucrose 20 mg Fe/mL for IV injection
Overall Study STARTED	196	97
Overall Study COMPLETED	142	74
Overall Study NOT COMPLETED	54	23

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Compare Efficacy/Safety of Repeat Doses of Ferumoxytol With Iron Sucrose in CKD Subjects With IDA and on Hemodialysis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ferumoxytol n=196 Participants 30 mg Fe/mL for IV injection	Iron Sucrose n=97 Participants 20 mg Fe/mL for IV injection	Total n=293 Participants Total of all reporting groups
Age, Continuous	59.3 years STANDARD_DEVIATION 14.13 • n=5 Participants	57.6 years STANDARD_DEVIATION 13.62 • n=7 Participants	58.8 years STANDARD_DEVIATION 13.96 • n=5 Participants
Sex: Female, Male Female	82 Participants n=5 Participants	40 Participants n=7 Participants	122 Participants n=5 Participants
Sex: Female, Male Male	114 Participants n=5 Participants	57 Participants n=7 Participants	171 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	68 Participants n=5 Participants	40 Participants n=7 Participants	108 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	128 Participants n=5 Participants	57 Participants n=7 Participants	185 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	10 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) Asian	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Black or African American	62 Participants n=5 Participants	26 Participants n=7 Participants	88 Participants n=5 Participants
Race (NIH/OMB) White	101 Participants n=5 Participants	47 Participants n=7 Participants	148 Participants n=5 Participants
Race (NIH/OMB) More than one race	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	185 participants n=5 Participants	90 participants n=7 Participants	275 participants n=5 Participants
Region of Enrollment Canada	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment United Kingdom	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
Mean Hemoglobin	10.4 g/dL STANDARD_DEVIATION 0.74 • n=5 Participants	10.4 g/dL STANDARD_DEVIATION 0.81 • n=7 Participants	10.4 g/dL STANDARD_DEVIATION 0.76 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 treatment periods (5 weeks per treatment period)

Population: Mean Change in Hemoglobin at Week 5 - ITT Population

Changes in the mean hemoglobin between Baseline and Week 5 for ferumoxytol and iron sucrose in each treatment period.

Outcome measures

Outcome measures
Measure	Ferumoxytol n=196 Participants 30 mg Fe/mL for IV injection	Iron Sucrose n=97 Participants 20 mg Fe/mL for IV injection
Hemoglobin Changes TP3	0.6 g/dL Standard Deviation 1.10	0.4 g/dL Standard Deviation 0.87
Hemoglobin Changes TP1	0.5 g/dL Standard Deviation 0.97	0.4 g/dL Standard Deviation 0.97
Hemoglobin Changes TP2	0.6 g/dL Standard Deviation 0.96	0.3 g/dL Standard Deviation 1.03
Hemoglobin Changes TP4	0.5 g/dL Standard Deviation 1.12	0.6 g/dL Standard Deviation 1.11
Hemoglobin Changes TP5	0.4 g/dL Standard Deviation 1.14	0.3 g/dL Standard Deviation 0.96
Hemoglobin Changes TP6	0.5 g/dL Standard Deviation 1.21	-0.3 g/dL Standard Deviation 1.00

SECONDARY outcome

Timeframe: Up to 6 treatment periods (5 weeks per treatment period)

Population: Mean Change in TSAT at Week 5 - ITT Population

Mean change in TSAT from TP Baseline to Week 5 for each TP

Outcome measures

Outcome measures
Measure	Ferumoxytol n=195 Participants 30 mg Fe/mL for IV injection	Iron Sucrose n=95 Participants 20 mg Fe/mL for IV injection
Changes in Transferrin Saturation (TSAT) TP1	6.6 Percent Standard Deviation 9.2	9.5 Percent Standard Deviation 11.97
Changes in Transferrin Saturation (TSAT) TP2	8.2 Percent Standard Deviation 12.95	11.3 Percent Standard Deviation 14.68
Changes in Transferrin Saturation (TSAT) TP3	8.5 Percent Standard Deviation 10.56	9.1 Percent Standard Deviation 11.13
Changes in Transferrin Saturation (TSAT) TP4	9.8 Percent Standard Deviation 14.76	10.0 Percent Standard Deviation 14.76
Changes in Transferrin Saturation (TSAT) TP5	6.3 Percent Standard Deviation 9.77	14.4 Percent Standard Deviation 17.05
Changes in Transferrin Saturation (TSAT) TP6	7.1 Percent Standard Deviation 16.62	5.1 Percent Standard Deviation 12.84

SECONDARY outcome

Timeframe: Up to 6 treatment periods (5 weeks per treatment period)

Population: ITT population

The proportion of subjects by group achieving a ≥1.0 g/dL increase in hemoglobin at any point during each 5-week treatment period.

Outcome measures

Outcome measures
Measure	Ferumoxytol n=196 Participants 30 mg Fe/mL for IV injection	Iron Sucrose n=97 Participants 20 mg Fe/mL for IV injection
Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP TP4	20 participants	10 participants
Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP TP1	55 participants	23 participants
Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP TP2	55 participants	13 participants
Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP TP3	42 participants	19 participants
Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP TP5	13 participants	3 participants
Proportion of Subjects With an Increase in Hemoglobin of ≥1.0 g/dL at Any Time From TP Baseline to Week 5 for Each TP TP6	5 participants	1 participants

Adverse Events

Ferumoxytol

Serious events: 93 serious events

Other events: 158 other events

Deaths: 16 deaths

Iron Sucrose

Serious events: 49 serious events

Other events: 81 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Information

AMAG Pharmaceuticals

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If there is no multi-site publication within 18 months after the Study has been completed or terminated at all Study sites, and all data have been received by Sponsor, the Site, and SMO shall have the right to publish its results from the Study for non-commercial purposes, if submitted to Sponsor for review 60 days prior to submission of publication. Publication must remove all confidential information and may be delayed by up to 180 days to allow Sponsor to protect its interests.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ferumoxytol n=196 participants at risk 30 mg Fe/mL for IV injection	Iron Sucrose n=97 participants at risk 20 mg Fe/mL for IV injection
Infections and infestations Infections and infestations	19.4% 38/196 • Number of events 49 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	17.5% 17/97 • Number of events 24 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Infections and infestations Sepsis	5.1% 10/196 • Number of events 10 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	2.1% 2/97 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Infections and infestations Pneumonia	3.6% 7/196 • Number of events 7 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	3.1% 3/97 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Infections and infestations Cellulitis	2.0% 4/196 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	2.1% 2/97 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Gastrointestinal disorders Gastrointestinal disorders	12.8% 25/196 • Number of events 32 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	12.4% 12/97 • Number of events 21 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Gastrointestinal disorders Abdominal pain	1.0% 2/196 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	4.1% 4/97 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.5% 3/196 • Number of events 3 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	1.0% 1/97 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Gastrointestinal disorders Vomiting	0.51% 1/196 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	3.1% 3/97 • Number of events 3 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Gastrointestinal disorders Nausea	0.00% 0/196 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	3.1% 3/97 • Number of events 3 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Cardiac disorders Cardiac disorders	10.2% 20/196 • Number of events 31 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	15.5% 15/97 • Number of events 27 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Cardiac disorders Cardiac failure congestive	2.6% 5/196 • Number of events 5 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	5.2% 5/97 • Number of events 7 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Cardiac disorders Acute myocardial infarction	2.0% 4/196 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	3.1% 3/97 • Number of events 6 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Cardiac disorders Angina pectoris	1.5% 3/196 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	4.1% 4/97 • Number of events 6 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Cardiac disorders Cardiac arrest	1.5% 3/196 • Number of events 5 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	2.1% 2/97 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Cardiac disorders Cardio-respiratory arrest	2.0% 4/196 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	1.0% 1/97 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	9.2% 18/196 • Number of events 22 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	16.5% 16/97 • Number of events 20 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	2.0% 4/196 • Number of events 5 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	4.1% 4/97 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Injury, poisoning and procedural complications Hip fracture	1.5% 3/196 • Number of events 3 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	0.00% 0/97 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	10.7% 21/196 • Number of events 27 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	6.2% 6/97 • Number of events 9 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	3.6% 7/196 • Number of events 7 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	2.1% 2/97 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	3.1% 6/196 • Number of events 7 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	2.1% 2/97 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.0% 4/196 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	1.0% 1/97 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.5% 3/196 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	0.00% 0/97 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Metabolism and nutrition disorders Metabolism and nutrition disorders	8.7% 17/196 • Number of events 18 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	10.3% 10/97 • Number of events 21 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Metabolism and nutrition disorders Fluid overload	4.6% 9/196 • Number of events 10 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	4.1% 4/97 • Number of events 9 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Metabolism and nutrition disorders Hyperkalaemia	2.6% 5/196 • Number of events 5 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	4.1% 4/97 • Number of events 6 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Metabolism and nutrition disorders Hypoglycaemia	1.0% 2/196 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	3.1% 3/97 • Number of events 3 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Vascular disorders Vascular disorders	6.1% 12/196 • Number of events 14 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	13.4% 13/97 • Number of events 14 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Nervous system disorders Nervous system disorders	6.6% 13/196 • Number of events 16 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	9.3% 9/97 • Number of events 12 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
General disorders General disorders and administration site conditions	4.6% 9/196 • Number of events 10 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	6.2% 6/97 • Number of events 6 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
General disorders Non-cardiac chest pain	2.6% 5/196 • Number of events 5 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	2.1% 2/97 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Blood and lymphatic system disorders Blood and lymphatic system disorders	3.6% 7/196 • Number of events 8 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	5.2% 5/97 • Number of events 5 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Blood and lymphatic system disorders Anaemia	2.0% 4/196 • Number of events 5 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	4.1% 4/97 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Psychiatric disorders Psychiatric disorders	3.1% 6/196 • Number of events 11 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	2.1% 2/97 • Number of events 3 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Psychiatric disorders Mental status changes	2.6% 5/196 • Number of events 10 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	1.0% 1/97 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	1.5% 3/196 • Number of events 6 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	3.1% 3/97 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	1.0% 2/196 • Number of events 3 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	1.0% 1/97 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Immune system disorders Immune system disorders	1.0% 2/196 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	1.0% 1/97 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	0.51% 1/196 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	1.0% 1/97 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Investigations Investigations	0.00% 0/196 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	2.1% 2/97 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Ear and labyrinth disorders Ear and labyrinth disorders	0.00% 0/196 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	2.1% 2/97 • Number of events 3 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.

Measure	Ferumoxytol n=196 participants at risk 30 mg Fe/mL for IV injection	Iron Sucrose n=97 participants at risk 20 mg Fe/mL for IV injection
Gastrointestinal disorders Gastrointestinal disorders	37.8% 74/196 • Number of events 163 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	37.1% 36/97 • Number of events 85 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Gastrointestinal disorders Nausea	11.2% 22/196 • Number of events 30 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	15.5% 15/97 • Number of events 17 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Gastrointestinal disorders Diarrhoea	10.7% 21/196 • Number of events 25 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	12.4% 12/97 • Number of events 13 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Gastrointestinal disorders Vomiting	8.2% 16/196 • Number of events 20 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	12.4% 12/97 • Number of events 15 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Gastrointestinal disorders Abdominal pain	6.1% 12/196 • Number of events 14 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	8.2% 8/97 • Number of events 9 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	31.1% 61/196 • Number of events 135 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	43.3% 42/97 • Number of events 101 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Injury, poisoning and procedural complications Arteriovenous fistula site complication	7.1% 14/196 • Number of events 18 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	8.2% 8/97 • Number of events 25 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	3.6% 7/196 • Number of events 8 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	7.2% 7/97 • Number of events 7 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Injury, poisoning and procedural complications Fall	3.6% 7/196 • Number of events 7 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	6.2% 6/97 • Number of events 6 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Infections and infestations Infections and infestations	32.7% 64/196 • Number of events 112 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	34.0% 33/97 • Number of events 61 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Infections and infestations Upper respiratory tract infection	7.1% 14/196 • Number of events 14 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	6.2% 6/97 • Number of events 7 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Infections and infestations Urinary tract infection	6.1% 12/196 • Number of events 12 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	3.1% 3/97 • Number of events 3 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Infections and infestations Pneumonia	5.6% 11/196 • Number of events 12 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	3.1% 3/97 • Number of events 4 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Infections and infestations Sepsis	5.1% 10/196 • Number of events 10 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	2.1% 2/97 • Number of events 2 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Infections and infestations Cellulitis	2.6% 5/196 • Number of events 5 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	6.2% 6/97 • Number of events 7 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Gastrointestinal disorders General disorders and administration site conditions	29.1% 57/196 • Number of events 87 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	21.6% 21/97 • Number of events 37 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
General disorders Non-cardiac chest pain	5.1% 10/196 • Number of events 11 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	7.2% 7/97 • Number of events 12 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
General disorders Pyrexia	7.7% 15/196 • Number of events 17 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	1.0% 1/97 • Number of events 1 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	20.4% 40/196 • Number of events 127 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	25.8% 25/97 • Number of events 82 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	6.6% 13/196 • Number of events 16 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	11.3% 11/97 • Number of events 22 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	8.2% 16/196 • Number of events 70 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	7.2% 7/97 • Number of events 37 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Musculoskeletal and connective tissue disorders Arthralgia	4.1% 8/196 • Number of events 8 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	7.2% 7/97 • Number of events 10 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Vascular disorders Vascular disorders	19.4% 38/196 • Number of events 77 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	24.7% 24/97 • Number of events 38 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Vascular disorders Hypotension	8.7% 17/196 • Number of events 21 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	7.2% 7/97 • Number of events 8 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Vascular disorders Hypertension	7.1% 14/196 • Number of events 37 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	6.2% 6/97 • Number of events 14 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Nervous system disorders Nervous system disorders	17.9% 35/196 • Number of events 48 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	24.7% 24/97 • Number of events 48 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Nervous system disorders Dizziness	5.1% 10/196 • Number of events 11 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	7.2% 7/97 • Number of events 18 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Nervous system disorders Headache	4.1% 8/196 • Number of events 12 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	7.2% 7/97 • Number of events 9 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	20.9% 41/196 • Number of events 74 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	18.6% 18/97 • Number of events 30 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Respiratory, thoracic and mediastinal disorders Cough	6.1% 12/196 • Number of events 14 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	5.2% 5/97 • Number of events 5 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.6% 11/196 • Number of events 13 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	6.2% 6/97 • Number of events 6 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Cardiac disorders Cardiac disorders	15.3% 30/196 • Number of events 64 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	18.6% 18/97 • Number of events 33 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Cardiac disorders Cardiac failure congestive	3.1% 6/196 • Number of events 6 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	5.2% 5/97 • Number of events 7 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Metabolism and nutrition disorders Metabolism and nutrition disorders	16.3% 32/196 • Number of events 51 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	15.5% 15/97 • Number of events 29 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Metabolism and nutrition disorders Fluid overload	7.1% 14/196 • Number of events 15 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	6.2% 6/97 • Number of events 12 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Metabolism and nutrition disorders Hyperkalaemia	5.6% 11/196 • Number of events 11 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	5.2% 5/97 • Number of events 7 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	9.7% 19/196 • Number of events 32 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	10.3% 10/97 • Number of events 14 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Skin and subcutaneous tissue disorders Pruritus	6.1% 12/196 • Number of events 15 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	4.1% 4/97 • Number of events 5 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Psychiatric disorders Psychiatric disorders	9.2% 18/196 • Number of events 30 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	7.2% 7/97 • Number of events 11 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Investigations Investigations	5.6% 11/196 • Number of events 12 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	13.4% 13/97 • Number of events 21 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Blood and lymphatic system disorders Blood and lymphatic system disorders	7.1% 14/196 • Number of events 20 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	6.2% 6/97 • Number of events 6 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.
Blood and lymphatic system disorders Anaemia	4.1% 8/196 • Number of events 12 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.	5.2% 5/97 • Number of events 5 • Reported Adverse Events (AEs) include events starting on or after day 0 up to 13 months Safety population included all patients who received any study drug.