Trial Outcomes & Findings for A Phase 3, Long-Term Safety Study of Intravenous Epoetin Hospira in Patients With Chronic Renal Failure Requiring Hemodialysis and Receiving Epoetin Maintenance Treatment. AiME - Anemia Management With Epoetin (NCT NCT01628107)

Last Updated: 2018-07-19

Results Overview

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

406 participants

Primary outcome timeframe

Up through 7 days after first dose of study drug (Week 1)

Results posted on

2018-07-19

Participant Flow

Participants with chronic renal failure were receiving Epoetin maintenance therapy in study EPOE-10-01 (NCT01473407) prior to enrollment and treatment in the current study.

Participant milestones

Participant milestones
Measure	Epoetin Hospira Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Overall Study STARTED	414
Overall Study Treated	406
Overall Study COMPLETED	295
Overall Study NOT COMPLETED	119

Reasons for withdrawal

Reasons for withdrawal
Measure	Epoetin Hospira Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Overall Study Withdrawal by Subject	17
Overall Study Lost to Follow-up	4
Overall Study Adverse Event	33
Overall Study Physician Decision	2
Overall Study Not met Inclusion/Exclusion Criteria	1
Overall Study Non-compliant with Study Procedures	10
Overall Study Not Treated	8
Overall Study Sponsor Decision	11
Overall Study Missed Study Drug More than 2 Weeks	7
Overall Study Relocated	8
Overall Study Kidney Transplant	9
Overall Study Use of Standard of Care	9

Baseline Characteristics

A Phase 3, Long-Term Safety Study of Intravenous Epoetin Hospira in Patients With Chronic Renal Failure Requiring Hemodialysis and Receiving Epoetin Maintenance Treatment. AiME - Anemia Management With Epoetin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Epoetin Hospira n=406 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Age, Continuous	57.45 years STANDARD_DEVIATION 12.062 • n=93 Participants
Sex: Female, Male Female	169 Participants n=93 Participants
Sex: Female, Male Male	237 Participants n=93 Participants

PRIMARY outcome

Timeframe: Up through 7 days after first dose of study drug (Week 1)

Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, "number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=400 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Percentage of Participants With Treatment Emergent Adverse Events (AEs): Week 1	13.0 Percentage of participants

PRIMARY outcome

Timeframe: Week 1 up to Week 12

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=406 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 1 to 12	59.4 Percentage of participants

PRIMARY outcome

Timeframe: Week 13 up to Week 24

Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, ''number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=369 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 13 to 24	57.5 Percentage of participants

PRIMARY outcome

Timeframe: Week 25 up to Week 36

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=339 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 25 to 36	54.3 Percentage of participants

PRIMARY outcome

Timeframe: Week 37 up to Week 48

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=315 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 37 to 48	51.7 Percentage of participants

PRIMARY outcome

Timeframe: Week 1 up to Week 48

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=406 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 1 to 48	85.7 Percentage of participants

SECONDARY outcome

Timeframe: Week 1 up to Week 48

Population: Full analysis set (FAS) included all enrolled participants and had at least 1 dose of Epoetin Hospira study drug and had at least 1 Hb value. Here, "number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=400 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Mean Weekly Dosage of Epoetin Hospira : Over Week 1 to 48	95.30 Unit per kilogram per week (U/kg/week) Standard Deviation 85.515

SECONDARY outcome

Timeframe: Week 1 up to Week 12; Week 13 up to Week 24; Week 25 up to Week 36; Week 37 up to Week 48

Population: FAS included all enrolled participants and had at least 1 dose of Epoetin Hospira study drug and had at least 1 Hb value.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=403 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Mean Weekly Dosage of Epoetin Hospira for Interval of 12 Weeks Week 1 to Week 12	94.93 U/kg/week Standard Deviation 89.219
Mean Weekly Dosage of Epoetin Hospira for Interval of 12 Weeks Week 13 to Week 24	94.84 U/kg/week Standard Deviation 89.303
Mean Weekly Dosage of Epoetin Hospira for Interval of 12 Weeks Week 25 to Week 36	94.01 U/kg/week Standard Deviation 86.0
Mean Weekly Dosage of Epoetin Hospira for Interval of 12 Weeks Week 37 to Week 48	99.55 U/kg/week Standard Deviation 95.510

SECONDARY outcome

Timeframe: Week 1 up to Week 48

Population: FAS included all enrolled participants and had at least 1 dose of Epoetin Hospira study drug and had at least 1 Hb value. Here, "number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=402 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Mean Hemoglobin Levels: Over Week 1 to 48	10.21 g/dL Standard Deviation 0.629

SECONDARY outcome

Timeframe: Week 1 up to Week 12; Week 13 up to Week 24; Week 25 up to Week 36; Week 37 up to Week 48

Population: FAS included all enrolled participants and had at least 1 dose of Epoetin Hospira study drug and had at least 1 Hb value.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=402 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Mean Hemoglobin Levels for Interval of 12 Weeks Week 1 to Week 12	10.26 g/dL Standard Deviation 0.789
Mean Hemoglobin Levels for Interval of 12 Weeks Week 13 to Week 24	10.25 g/dL Standard Deviation 0.762
Mean Hemoglobin Levels for Interval of 12 Weeks Week 25 to Week 36	10.18 g/dL Standard Deviation 0.865
Mean Hemoglobin Levels for Interval of 12 Weeks Week 37 to Week 48	10.21 g/dL Standard Deviation 0.818

SECONDARY outcome

Timeframe: Week 1 up to Week 48

Hematocrit is defined as the percentage of red blood cells in the blood.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=402 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Mean Hematocrit Levels: Over Week 1 to 48	32.17 Percentage of red blood cells Standard Deviation 2.164

SECONDARY outcome

Timeframe: Week 1 up to Week 12; Week 13 up to Week 24; Week 25 up to Week 36; Week 37 up to Week 48

Population: FAS included all enrolled participants and had at least 1 dose of Epoetin Hospira study drug and had at least 1 Hb value.

Hematocrit is defined as the percentage of red blood cells in the blood.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=403 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Mean Hematocrit Levels for Interval of 12 Weeks Week 1 to Week 12	32.26 Percentage of red blood cells Standard Deviation 2.695
Mean Hematocrit Levels for Interval of 12 Weeks Week 13 to Week 24	32.21 Percentage of red blood cells Standard Deviation 2.569
Mean Hematocrit Levels for Interval of 12 Weeks Week 25 to Week 36	32.03 Percentage of red blood cells Standard Deviation 2.978
Mean Hematocrit Levels for Interval of 12 Weeks Week 37 to Week 48	32.17 Percentage of red blood cells Standard Deviation 2.738

SECONDARY outcome

Timeframe: Week 1 up to Week 48

Population: FAS included all enrolled participants and had at least 1 dose of Epoetin Hospira study drug and had at least 1 Hb value.

Percentage of participants with hemoglobin level outside the target range of 9.0 to 11.0 g/dL were reported.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=403 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Percentage of Participants With Hemoglobin Level Outside the Target Range	90.1 Percentage of participants

SECONDARY outcome

Timeframe: Week 1 up to Week 48

Population: FAS included all enrolled participants and had at least 1 dose of Epoetin Hospira study drug and had at least 1 Hb value.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=403 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Percentage of Participants Who Received Blood Transfusions	9.7 Percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 up to Week 48

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=402 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Percentage of Participants With Hemoglobin Level Less Than (<) 8.0 Gram Per Deciliter (g/dL)	13.9 Percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 up to Week 48

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=402 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Percentage of Participants With Hemoglobin Level Greater Than (>) 12.0 Gram Per Deciliter (g/dL)	20.9 Percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 48

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Participants with clinically significant change from baseline in hemoglobin levels were upon investigator's discretion.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=406 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Number of Participants With Clinically Significant Change From Baseline in Hemoglobin Levels	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 up to Week 48

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=406 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Number of Participants Who Received Concomitant Medication	406 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 48

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Laboratory tests included: Hematology (hematocrit, hemoglobin, red blood cells count, reticulocytes, white blood cells count, neutrophils, bands, lymphocytes, monocytes, basophils, eosinophils, platelets, mean corpuscular volume); Coagulation panel (prothrombin time, international normalized ratio, activated partial thromboplastin time); Chemistry (blood urine nitrogen, creatinine, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, calcium, gamma-glutyl transpeptidase, phosphorus, uric acid, total protein, glucose, albumin, C-reactive protein); iron status (plasma ferritin, transferrin saturation). Participants with clinically significant change from baseline in laboratory tests were based on investigator's discretion.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=406 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Number of Participants With Clinically Significant Change From Baseline in Laboratory Tests	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 48

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

ECG parameters included: PR interval, QRS complex, QT interval and QTC interval. Participants with clinically significant change from baseline in 12-lead ECGs were based on investigator's discretion.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=406 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Number of Participants With Clinically Significant Change From Baseline in 12-Lead Electrocardiogram (ECG)	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 48

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Physical examination included examination of the skin, eyes, ears, nose, throat, head, neck, thyroid, lungs, chest, abdomen, extremities, lymphatic, cardiovascular, musculoskeletal and neurological systems. Participants for any clinically significant changes in physical examination were based on the investigator's discretion.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=406 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Number of Participants With Clinically Significant Change From Baseline in Physical Examinations	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 48

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Percentage of participants with at least 1 positive anti-rhEPO antibody were reported. Radioimmunoprecipitation assay was used to determine the presence of anti-rhEPO antibodies.

Outcome measures

Outcome measures
Measure	Epoetin Hospira n=406 Participants Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Percentage of Participants With Anti-Recombinant Human Erythropoietin (Anti-rhEPO) Antibodies Baseline	0 Percentage of participants
Percentage of Participants With Anti-Recombinant Human Erythropoietin (Anti-rhEPO) Antibodies Week 48	0.6 Percentage of participants

Adverse Events

Epoetin Hospira

Serious events: 168 serious events

Other events: 277 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Epoetin Hospira n=406 participants at risk Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Blood and lymphatic system disorders Anaemia	0.99% 4/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Blood and lymphatic system disorders Pancytopenia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Acute coronary syndrome	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Acute myocardial infarction	3.2% 13/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Angina pectoris	1.7% 7/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Aortic valve incompetence	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Atrial fibrillation	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Bradycardia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Cardiac arrest	1.5% 6/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Cardiac failure	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Cardiac failure congestive	2.5% 10/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Cardio-respiratory arrest	1.7% 7/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Cardiomegaly	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Coronary artery disease	0.99% 4/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Coronary artery occlusion	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Hypertrophic cardiomyopathy	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Myocardial infarction	0.99% 4/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Myocardial ischaemia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Sinus bradycardia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Sinus tachycardia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Tachycardia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Ventricular fibrillation	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Cardiac disorders Ventricular tachycardia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Congenital, familial and genetic disorders Gastrointestinal angiodysplasia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Congenital, familial and genetic disorders Gastrointestinal arteriovenous malformation	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Endocrine disorders Thyroid mass	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Abdominal pain	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Abdominal pain upper	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Colitis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Colitis ischaemic	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Colonic polyp	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Diarrhoea	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Dysphagia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Gastritis	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Hiatus hernia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Ileus	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Pancreatitis	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Retroperitoneal haemorrhage	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Small intestinal obstruction	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Localised intraabdominal fluid collection	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Rectal haemorrhage	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Small intestinal haemorrhage	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Vomiting	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
General disorders Asthenia	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
General disorders Chest pain	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
General disorders Death	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
General disorders Non-cardiac chest pain	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
General disorders Pyrexia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
General disorders Systemic inflammatory response syndrome	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Hepatobiliary disorders Cholecystitis	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Hepatobiliary disorders Cholecystitis acute	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Hepatobiliary disorders Cholelithiasis	1.2% 5/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Hepatobiliary disorders Hepatic cirrhosis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Cellulitis	0.99% 4/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Osteomyelitis	0.99% 4/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Pneumonia	3.9% 16/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Sepsis	4.4% 18/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Staphylococcal sepsis	0.99% 4/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Abdominal abscess	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Abscess limb	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Appendicitis	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Appendicitis perforated	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Arteriovenous fistula site infection	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Arteriovenous graft site infection	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Bacteraemia	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Bronchitis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Cardiac valve abscess	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Cellulitis staphylococcal	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Cystitis escherichia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Device related infection	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Device related sepsis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Diverticulitis	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Endocarditis	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Gangrene	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Gastroenteritis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Infected skin ulcer	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Influenza	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Liver abscess	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Lobar pneumonia	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Localised infection	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Mastoiditis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Staphylococcal bacteraemia	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Nocardiosis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Otitis externa	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Otitis media	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Peridiverticular abscess	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Perirectal abscess	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Pneumonia viral	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Pyelonephritis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Sepsis syndrome	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Septic shock	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Staphylococcal infection	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Streptococcal bacteraemia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Upper respiratory tract infection	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Urinary tract infection	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Urosepsis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Accidental overdose	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Ankle fracture	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Arteriovenous fistula site complication	0.99% 4/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Arteriovenous fistula site haemorrhage	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Clavicle fracture	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Fall	0.99% 4/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Femur fracture	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Fibula fracture	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Head injury	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Laceration	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Overdose	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Spinal compression fracture	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Splenic rupture	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Sternal fracture	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Tendon rupture	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Tibia fracture	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Toxicity to various agents	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Traumatic haemorrhage	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Vascular graft complication	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Vascular graft thrombosis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Vascular pseudoaneurysm	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Vascular pseudoaneurysm ruptured	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Investigations Liver function test abnormal	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Metabolism and nutrition disorders Dehydration	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Metabolism and nutrition disorders Diabetes mellitus	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Metabolism and nutrition disorders Diabetic foot	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Metabolism and nutrition disorders Fluid overload	1.2% 5/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Metabolism and nutrition disorders Hyperglycaemia	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Metabolism and nutrition disorders Hyperkalaemia	3.2% 13/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Metabolism and nutrition disorders Hypoglycaemia	1.5% 6/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Metabolism and nutrition disorders Hypercalcaemia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Back pain	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Chondrocalcinosis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Fibromyalgia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Mobility decreased	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Muscular weakness	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Neck pain	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Osteolysis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage IV	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer stage III	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Cerebrovascular accident	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Metabolic encephalopathy	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Carotid artery stenosis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Cerebral haemorrhage	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Cerebral infarction	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Cerebral ischaemia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Diabetic hyperosmolar coma	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Dizziness	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Encephalopathy	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Haemorrhage intracranial	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Hemiparesis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Hepatic encephalopathy	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Ischaemic stroke	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Mental impairment	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Presyncope	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Syncope	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Transient ischaemic attack	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Unresponsive to stimuli	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Psychiatric disorders Delirium	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Psychiatric disorders Hallucination	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Renal and urinary disorders Azotaemia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Renal and urinary disorders Hydronephrosis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Renal and urinary disorders Renal failure	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Renal and urinary disorders Renal failure chronic	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Reproductive system and breast disorders Dysfunctional uterine bleeding	0.59% 1/169 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Reproductive system and breast disorders Vaginal haemorrhage	0.59% 1/169 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.99% 4/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.99% 4/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Accelerated hypertension	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Aortic stenosis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Arterial thrombosis limb	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Deep vein thrombosis	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Hypertension	1.5% 6/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Hypertensive crisis	0.74% 3/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Hypertensive emergency	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Hypotension	0.49% 2/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Haematoma	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Ischaemic limb pain	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Malignant hypertension	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Peripheral arterial occlusive disease	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Peripheral ischaemia	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Peripheral vascular disorder	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Vascular occlusion	0.25% 1/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.

Other adverse events

Other adverse events
Measure	Epoetin Hospira n=406 participants at risk Participants were enrolled to receive Epoetin Hospira intravenous injection 1 to 3 times every week over a period of 48 weeks. Dose was adjusted to maintain the hemoglobin (Hb) level from 9 to 11 gram per deciliter (g/dL).
Musculoskeletal and connective tissue disorders Muscle spasms	20.0% 81/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Nausea	14.3% 58/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Headache	12.6% 51/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Diarrhoea	12.1% 49/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Nervous system disorders Dizziness	11.6% 47/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.3% 42/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Hypotension	10.1% 41/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Vomiting	9.6% 39/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Respiratory, thoracic and mediastinal disorders Cough	8.9% 36/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Injury, poisoning and procedural complications Arteriovenous fistula site complication	8.6% 35/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
General disorders Pyrexia	8.6% 35/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
General disorders Oedema peripheral	8.1% 33/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Blood and lymphatic system disorders Anaemia	6.2% 25/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Pain in extremity	5.9% 24/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Vascular disorders Hypertension	5.4% 22/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
General disorders Asthenia	5.2% 21/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Musculoskeletal and connective tissue disorders Back pain	5.2% 21/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Gastrointestinal disorders Constipation	5.2% 21/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.
Infections and infestations Upper respiratory tract infection	5.2% 21/406 The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety Population.

Additional Information

Pfizer, Inc.

Pfizer ClinicalTrials.gov Call Center

Phone: 1--800--718--1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single centre publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER