A Study of CSL112 in Adults With Moderate Renal Impairmen... | NCT02742103

NCT02742103

ID	Type	Description	Link
2015-003017-26	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
CSL_112	Experimental	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).	Biological: CSL_112
Placebo	Placebo Comparator	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.	Other: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
CSL_112	Biological	CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent of Participants With at Least One Occurrence of Treatment-emergent Renal Serious Adverse Events (SAEs) (SAF)	A renal SAE is defined as any SAE with a MedDRA preferred term included in the Acute Renal Failure narrow Standard MedDRA Query or a preferred term of renal tubular necrosis, renal cortical necrosis, renal necrosis, or renal papillary necrosis.	Up to 9 weeks
Percent of Participants With Treatment-emergent Acute Kidney Injury (AKI )	Acute kidney injury is defined as an absolute increase in serum creatinine from baseline ≥ 0.3 mg/dL during the Active Treatment Period that is sustained upon repeat measurement by the central laboratory no earlier than 24 hours after the elevated value. If no repeat value is obtained, a single serum creatinine value that is increased from baseline ≥ 0.3 mg/dL (26.5 μmol/L) during the Active Treatment Period would also fulfil the definition of AKI.	Up to 4 weeks

Measure	Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)		Up to 9 weeks
Percentage of Participants With TEAEs		Up to 9 weeks
Total Number of TEAEs

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Danielle Duffy, MD	CSL Behring	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Study Site 16101		Birmingham	Alabama	35211	United States
Study Site 16078

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33217027	Derived	Zheng B, Duffy D, Tricoci P, Kastrissios H, Pfister M, Wright SD, Gille A, Tortorici MA. Pharmacometric analyses to characterize the effect of CSL112 on apolipoprotein A-I and cholesterol efflux capacity in acute myocardial infarction patients. Br J Clin Pharmacol. 2021 Jun;87(6):2558-2571. doi: 10.1111/bcp.14666. Epub 2020 Dec 23.
30580130

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 6, 2016	May 26, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
BG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00070.6± 10.95 BG00171.9± 10.12 BG00271.1± 10.63

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

18-64 years

Title	Measurements
	BG00011 BG0014 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00018 BG00110 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

Netherlands

Title	Measurements
	BG0008 BG0012 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent of Participants With at Least One Occurrence of Treatment-emergent Renal Serious Adverse Events (SAEs) (SAF)

A renal SAE is defined as any SAE with a MedDRA preferred term included in the Acute Renal Failure narrow Standard MedDRA Query or a preferred term of renal tubular necrosis, renal cortical necrosis, renal necrosis, or renal papillary necrosis.

The Safety (SAF) Population consisted of all subjects who received at least a partial dose of investigational product.

Posted

Number

percentage of participants

Up to 9 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units	Counts
Participants	OG00052 OG00128

Title

Denominators

Categories

Title	Measurements
	OG0001.9 OG00114.3

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Newcombe-Wilson				Rate difference (CSL112 - placebo)	-0.124			2-Sided	95	-0.296	-0.005					Other

Primary

Percent of Participants With Treatment-emergent Acute Kidney Injury (AKI )

Acute kidney injury is defined as an absolute increase in serum creatinine from baseline ≥ 0.3 mg/dL during the Active Treatment Period that is sustained upon repeat measurement by the central laboratory no earlier than 24 hours after the elevated value. If no repeat value is obtained, a single serum creatinine value that is increased from baseline ≥ 0.3 mg/dL (26.5 μmol/L) during the Active Treatment Period would also fulfil the definition of AKI.

SAF

Posted

Number

percentage of participants

Up to 4 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units	Counts
Participants

Secondary

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

SAF

Posted

Number

participants

Up to 9 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With TEAEs

SAF

Posted

Number

percentage of participants

Up to 9 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units	Counts
Participants	OG000

Secondary

Total Number of TEAEs

SAF

Posted

Number

Number of TEAEs

Up to 9 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units	Counts
Participants	OG000

Secondary

Number of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR

Adverse drug reactions or suspected adverse drug reactions are defined as:

All TEAEs, including local tolerability events, that begin during or within 1 hour after the end of an infusion; or
Those TEAEs that the investigator or sponsor indicate may be causally related to product administration; or
All TEAEs for which the Investigator's causality assessment is missing or indeterminate; or
All TEAEs for which the incidence in an active treatment arm exceeds the exposure-adjusted incidence rate in the placebo arm by 30% or more, provided the difference in incidence rates is 1% or more.

SAF

Posted

Number

participants

Up to 9 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Secondary

Percentage of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR

Adverse drug reactions or suspected adverse drug reactions are defined as:

All TEAEs, including local tolerability events, that begin during or within 1 hour after the end of an infusion; or
Those TEAEs that the investigator or sponsor indicate may be causally related to product administration; or
All TEAEs for which the Investigator's causality assessment is missing or indeterminate; or
All TEAEs for which the incidence in an active treatment arm exceeds the exposure-adjusted incidence rate in the placebo arm by 30% or more, provided the difference in incidence rates is 1% or more.

SAF

Posted

Number

percentage of participants

Up to 9 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Secondary

Number of Participants With Change in Renal Status

Number of participants with changes in renal status defined as:

Absolute increases from baseline in serum creatinine as follows:

i. ≤ baseline value ii. > 0 to < 0.3 mg/dL iii. ≥ 0.3 to ≤ 0.5 mg/dL iv. > 0.5 mg/dL
Increases in serum creatinine that are sustained for ≥ 24 hours upon repeat measurement that are greater than or equal to 1.5 x, 2 x, or 3.0 x the baseline value, or serum creatinine ≥ 4.0 mg/dL
Initiation of renal replacement therapy
Decrease in eGFR ≥ 25% from baseline starting during the active treatment period and that is sustained at the final study visit

SAF

Posted

Number

participants

Baseline and up to 4 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units

Secondary

Percentage of Participants With Change in Renal Status

Percentage of participants with changes in renal status defined as:

Absolute increases from baseline in serum creatinine as follows:

i. ≤ baseline value ii. > 0 to < 0.3 mg/dL iii. ≥ 0.3 to ≤ 0.5 mg/dL iv. > 0.5 mg/dL
Increases in serum creatinine that are sustained for ≥ 24 hours upon repeat measurement that are greater than or equal to 1.5 x, 2 x, or 3.0 x the baseline value, or serum creatinine ≥ 4.0 mg/dL
Initiation of renal replacement therapy
Decrease in eGFR ≥ 25% from baseline starting during the active treatment period and that is sustained at the final study visit

SAF

Posted

Number

percentage of participants

Baseline and up to 4 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Secondary

Number of Participants With Change in Hepatic Status

Number of participants with a change from baseline in hepatic status and that is sustained for ≥ 24 hours upon repeat measurement, defined as:

Alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
ALT > 5 x ULN
ALT > 10 x ULN
Serum total bilirubin > 1.5 x ULN
Serum total bilirubin > 2 x ULN
Possible Hy's law cases, as defined in the FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009).

SAF

Posted

Number

participants

Baseline and up to 4 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units	Counts
Participants

Secondary

Percentage of Participants With Change in Hepatic Status

Percentage of participants with a change from baseline in hepatic status and that is sustained for ≥ 24 hours upon repeat measurement, defined as:

Alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
ALT > 5 x ULN
ALT > 10 x ULN
Serum total bilirubin > 1.5 x ULN
Serum total bilirubin > 2 x ULN
Possible Hy's law cases, as defined in the FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009).

SAF

Posted

Number

percentage of participants

Baseline and up to 4 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units	Counts
Participants

Secondary

Number of Participants With Treatment-emergent Bleeding Events

Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).

SAF

Posted

Number

participants

Up to 9 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Treatment-emergent Bleeding Events

Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).

SAF

Posted

Number

percentage of participants

Up to 9 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Binding Antibodies Specific to Apolipoprotein A-I (Apo-A1) and CSL112

SAF

Posted

Number

percentage of participants

Up to 9 weeks

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units	Counts
Participants	OG000

Secondary

Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 1 for apoA-I and PC

Posted

Mean

Standard Deviation

mg/dL

Immediately after end of infusion

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units	Counts
Participants	OG000

Secondary

Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 4 for apoA-I and PC

Posted

Mean

Standard Deviation

mg/dL

Immediately after end of infusion

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
OG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)

Units	Counts
Participants	OG000

Secondary

Plasma apoA-I and Phosphatidylcholine (PC) Accumulation Ratio After Infusion 4

The plasma apoA-I and PC accumulation ratio will be determined for CSL112-treated subjects.

Pharmacokinetic Population (PK) consists of all subjects in the SAF who had at least 1 measurable plasma concentration of either apoA-I or PC.

Posted

Mean

Standard Deviation

mg/dL

Immediately after end of infusion

ID	Title	Description
OG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	CSL_112	CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total). CSL_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	2	52	12	52	18	52
EG001	Placebo	Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)	2	28	10	28	12	28

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0011 events1 affected28 at risk
Post concussion syndrome	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0010 events0 affected28 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0011 events1 affected28 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected52 at risk EG0010 events0 affected28 at risk
Cardiac failure	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected52 at risk EG0010 events0 affected28 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0010 events0 affected28 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0011 events1 affected28 at risk
Angina unstable	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0011 events1 affected28 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0010 events0 affected28 at risk
Sinus node dysfunction	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0010 events0 affected28 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0012 events2 affected28 at risk
Microcytic anaemia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0011 events1 affected28 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0010 events0 affected28 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0011 events1 affected28 at risk
Ataxia	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0010 events0 affected28 at risk
Syncope	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0011 events1 affected28 at risk
Visual impairment	Eye disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0010 events0 affected28 at risk
Death	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0011 events1 affected28 at risk
Vestibular disorder	Ear and labyrinth disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0010 events0 affected28 at risk
Gastrointestinal erosion	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0010 events0 affected28 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0010 events0 affected28 at risk
Nephropathy toxic	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0010 events0 affected28 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0012 events2 affected28 at risk
Renal failure	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0012 events1 affected28 at risk
Renal impairment	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0011 events1 affected28 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected52 at risk EG0010 events0 affected28 at risk
Bronchitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0011 events1 affected28 at risk
Pneumonia	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0011 events1 affected28 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0005 events5 affected52 at risk EG0011 events1 affected28 at risk
Blood creatinine increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0005 events5 affected52 at risk EG0010 events0 affected28 at risk
Haemoglobin decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected52 at risk EG0012 events2 affected28 at risk
Angina pectoris	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0005 events5 affected52 at risk EG0012 events2 affected28 at risk
Hypotension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0012 events2 affected28 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0013 events2 affected28 at risk
Non-cardiac chest pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0013 events3 affected28 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0004 events4 affected52 at risk EG0011 events1 affected28 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected52 at risk EG0012 events2 affected28 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected52 at risk EG0012 events2 affected28 at risk