Trial Outcomes & Findings for A Phase 2b Study of CSL112 in Subjects With Acute Myocardial Infarction. (NCT NCT02108262)

NCT ID: NCT02108262

Last Updated: 2021-03-15

Results Overview

A clinically important change in drug-induced liver injury is defined as a change (from baseline) in alanine aminotransferase (ALT) greater than 3 times the upper limit of normal (ULN) or a change in total bilirubin greater than 2 times ULN, that is confirmed upon repeat measurement.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 1267 participants
• Primary outcome timeframe: From baseline (before first infusion) to Day 29.
• Results posted on: 2021-03-15

Participant Flow

Participant milestones

Measure	Safety Lead-in [CSL112 (2 g)] In the safety lead-in, a small number of subjects (evenly stratified between subjects with normal renal function or mild renal impairment) were administered a single, 2 g infusion of CSL112.	CSL112 (2 g) CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Overall Study STARTED	9	419	421	418
Overall Study COMPLETED	9	375	379	376
Overall Study NOT COMPLETED	0	44	42	42

Reasons for withdrawal

Measure	Safety Lead-in [CSL112 (2 g)] In the safety lead-in, a small number of subjects (evenly stratified between subjects with normal renal function or mild renal impairment) were administered a single, 2 g infusion of CSL112.	CSL112 (2 g) CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Overall Study Non-compliance	0	2	1	1
Overall Study Randomized by error/screen failure	0	0	1	0
Overall Study Distance to center	0	1	1	0
Overall Study Adverse Event	0	11	6	12
Overall Study Death	0	2	2	1
Overall Study Lost to Follow-up	0	0	1	0
Overall Study Physician Decision	0	0	2	0
Overall Study Withdrawal by Subject	0	7	3	4
Overall Study Due to key hepatic values	0	1	0	0
Overall Study Unable to contact patient	0	3	1	2
Overall Study Patient unable to come to site/attend visit	0	6	11	6
Overall Study Patient did not want another infusion	0	3	3	2
Overall Study Vacation	0	1	0	0
Overall Study Patient decision	0	7	9	14
Overall Study Missed IV due to pharmacy error	0	0	1	0

Baseline Characteristics

A Phase 2b Study of CSL112 in Subjects With Acute Myocardial Infarction.

Baseline characteristics by cohort

Measure	Safety Lead-in [CSL112 (2 g)] n=9 Participants In the safety lead-in, a small number of subjects (evenly stratified between subjects with normal renal function or mild renal impairment) were administered a single, 2 g infusion of CSL112.	CSL112 (2 g) n=419 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=421 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=418 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)	Total n=1267 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	306 Participants n=7 Participants	296 Participants n=5 Participants	301 Participants n=4 Participants	910 Participants n=21 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	113 Participants n=7 Participants	125 Participants n=5 Participants	117 Participants n=4 Participants	357 Participants n=21 Participants
Age, Continuous	59.0 years STANDARD_DEVIATION 7.19 • n=5 Participants	57.7 years STANDARD_DEVIATION 10.15 • n=7 Participants	59.2 years STANDARD_DEVIATION 9.87 • n=5 Participants	58.1 years STANDARD_DEVIATION 10.57 • n=4 Participants	58.3 years STANDARD_DEVIATION 10.21 • n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	82 Participants n=7 Participants	98 Participants n=5 Participants	77 Participants n=4 Participants	259 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	337 Participants n=7 Participants	323 Participants n=5 Participants	341 Participants n=4 Participants	1008 Participants n=21 Participants
Region of Enrollment Hungary	9 participants n=5 Participants	66 participants n=7 Participants	67 participants n=5 Participants	69 participants n=4 Participants	211 participants n=21 Participants
Region of Enrollment United States	0 participants n=5 Participants	59 participants n=7 Participants	54 participants n=5 Participants	54 participants n=4 Participants	167 participants n=21 Participants
Region of Enrollment Czechia	0 participants n=5 Participants	33 participants n=7 Participants	35 participants n=5 Participants	36 participants n=4 Participants	104 participants n=21 Participants
Region of Enrollment United Kingdom	0 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	4 participants n=4 Participants	9 participants n=21 Participants
Region of Enrollment Spain	0 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	6 participants n=4 Participants	17 participants n=21 Participants
Region of Enrollment Canada	0 participants n=5 Participants	9 participants n=7 Participants	9 participants n=5 Participants	7 participants n=4 Participants	25 participants n=21 Participants
Region of Enrollment Austria	0 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	2 participants n=4 Participants	7 participants n=21 Participants
Region of Enrollment Netherlands	0 participants n=5 Participants	48 participants n=7 Participants	48 participants n=5 Participants	49 participants n=4 Participants	145 participants n=21 Participants
Region of Enrollment Denmark	0 participants n=5 Participants	8 participants n=7 Participants	10 participants n=5 Participants	10 participants n=4 Participants	28 participants n=21 Participants
Region of Enrollment Poland	0 participants n=5 Participants	70 participants n=7 Participants	69 participants n=5 Participants	65 participants n=4 Participants	204 participants n=21 Participants
Region of Enrollment Italy	0 participants n=5 Participants	7 participants n=7 Participants	7 participants n=5 Participants	8 participants n=4 Participants	22 participants n=21 Participants
Region of Enrollment Israel	0 participants n=5 Participants	27 participants n=7 Participants	27 participants n=5 Participants	27 participants n=4 Participants	81 participants n=21 Participants
Region of Enrollment Australia	0 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	6 participants n=4 Participants	18 participants n=21 Participants
Region of Enrollment Bulgaria	0 participants n=5 Participants	47 participants n=7 Participants	47 participants n=5 Participants	46 participants n=4 Participants	140 participants n=21 Participants
Region of Enrollment France	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	1 participants n=4 Participants	3 participants n=21 Participants
Region of Enrollment Germany	0 participants n=5 Participants	28 participants n=7 Participants	30 participants n=5 Participants	28 participants n=4 Participants	86 participants n=21 Participants
Renal function from Interactive Web Response System (IWRS) Normal renal function	4 participants n=5 Participants	195 participants n=7 Participants	192 participants n=5 Participants	191 participants n=4 Participants	582 participants n=21 Participants
Renal function from Interactive Web Response System (IWRS) Mild renal impairment	5 participants n=5 Participants	224 participants n=7 Participants	229 participants n=5 Participants	227 participants n=4 Participants	685 participants n=21 Participants

PRIMARY outcome

Timeframe: From baseline (before first infusion) to Day 29.

Population: The Safety population (SP) comprised all subjects who were randomized into the main study or PK/PD substudy and received at least a partial infusion of the investigational product.

A clinically important change in drug-induced liver injury is defined as a change (from baseline) in alanine aminotransferase (ALT) greater than 3 times the upper limit of normal (ULN) or a change in total bilirubin greater than 2 times ULN, that is confirmed upon repeat measurement.

Outcome measures

Measure	CSL112 (2 g) n=415 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=416 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=413 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Percent of Participants With Clinically Important Change in Drug-induced Liver Injury	1.0 percentage of participants	0.5 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: From baseline (before first infusion) to Day 29.

Population: SP

A clinically important change in renal status is defined as a serum creatinine (Cr) increase to ≥ 1.5 x the baseline value that is confirmed upon repeat measurement.

Outcome measures

Measure	CSL112 (2 g) n=415 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=416 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=413 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Percent of Participants With Clinically Important Change in Renal Status	0 percentage of participants	0.7 percentage of participants	0.2 percentage of participants

SECONDARY outcome

Timeframe: From the start of the first infusion up to approximately 382 days

Population: The Intent-to-Treat (ITT) population comprised all subjects who were randomized to one of the three treatment groups for the Main Study or PK/PD substudy.

The MACE is a 4-component composite comprised of the time to the first of the following events: CV death, nonfatal myocardial infarction, ischemic stroke (non-hemorrhagic), and hospitalization for unstable angina.

Outcome measures

Measure	CSL112 (2 g) n=419 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=421 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=418 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
The Percentage of Participants With a Time-to-first Major Adverse Cardiovascular Event (MACE)	6.4 percentage of participants	5.7 percentage of participants	5.5 percentage of participants

SECONDARY outcome

Timeframe: Before first infusion and end of first infusion

Population: The pharmacokinetic population (PK) comprised all subjects who received at least 1 infusion of investigational product and had at least 1 post baseline measurable plasma concentration of apoA-I or PC.

Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) are analytes of CSL112

Outcome measures

Measure	CSL112 (2 g) n=396 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=404 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=403 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants apoA-I	35.9 mg/dL Standard Deviation 22.13	136.1 mg/dL Standard Deviation 54.37	-4.7 mg/dL Standard Deviation 13.46
Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants PC	57.7 mg/dL Standard Deviation 31.12	180.4 mg/dL Standard Deviation 74.4	-1.2 mg/dL Standard Deviation 20.43

SECONDARY outcome

Timeframe: Before first infusion and end of fourth infusion

Population: PK

Outcome measures

Measure	CSL112 (2 g) n=366 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=370 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=370 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants apoA-I	52.1 mg/dL Standard Deviation 55.03	158.0 mg/dL Standard Deviation 55.07	5.4 mg/dL Standard Deviation 26.47
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants PC	48.7 mg/dL Standard Deviation 55.75	186.8 mg/dL Standard Deviation 79.39	-12.9 mg/dL Standard Deviation 42.05

SECONDARY outcome

Timeframe: Before first infusion and end of first infusion

Population: PK

apoA-I and PC are analytes of CSL112

Outcome measures

Measure	CSL112 (2 g) n=185 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=175 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=183 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function apoA-I	36.0 mg/dL Standard Deviation 25.35	134.5 mg/dL Standard Deviation 48.25	-4.0 mg/dL Standard Deviation 16.95
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function PC	58.0 mg/dL Standard Deviation 37.06	177.4 mg/dL Standard Deviation 67.93	-1.3 mg/dL Standard Deviation 25.74

SECONDARY outcome

Timeframe: Before first infusion and end of fourth infusion

Population: PK

apoA-I and PC are analytes of CSL112

Outcome measures

Measure	CSL112 (2 g) n=173 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=160 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=171 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function apoA-I	54.7 mg/dL Standard Deviation 74.94	154.3 mg/dL Standard Deviation 53.64	4.8 mg/dL Standard Deviation 28.19
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function PC	47.6 mg/dL Standard Deviation 64.67	182.0 mg/dL Standard Deviation 80.74	-12.3 mg/dL Standard Deviation 44.89

SECONDARY outcome

Timeframe: Before first infusion and end of first infusion

Population: PK

apoA-I and PC are analytes of CSL112

Outcome measures

Measure	CSL112 (2 g) n=189 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=212 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=203 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment apoA-I	35.9 mg/dL Standard Deviation 19.05	135.5 mg/dL Standard Deviation 59.05	-5.3 mg/dL Standard Deviation 9.7
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment PC	57.8 mg/dL Standard Deviation 24.71	180.6 mg/dL Standard Deviation 79.50	-0.8 mg/dL Standard Deviation 14.95

SECONDARY outcome

Timeframe: Before first infusion and end of fourth infusion

Population: PK

apoA-I and PC are analytes of CSL112

Outcome measures

Measure	CSL112 (2 g) n=171 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=195 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=183 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment apoA-I	49.3 mg/dL Standard Deviation 27.63	158.4 mg/dL Standard Deviation 56.19	6.0 mg/dL Standard Deviation 25.68
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment PC	50.6 mg/dL Standard Deviation 47.17	188.3 mg/dL Standard Deviation 79.39	-13.2 mg/dL Standard Deviation 40.08

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: The Pharmacokinetic/Pharmacodynamic (PK/PD) population was a subset of subjects from the main study who consented to participate in the PK/PD substudy.

Cmax is the maximal plasma concentration.

Outcome measures

Measure	CSL112 (2 g) n=24 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=21 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=18 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants apoA-I	42.6 mg/dL Standard Deviation 11.2	147.4 mg/dL Standard Deviation 31.9	7.1 mg/dL Standard Deviation 7.9
Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants PC	67.7 mg/dL Standard Deviation 19.2	196.4 mg/dL Standard Deviation 36.2	11.1 mg/dL Standard Deviation 15.2

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Cmax is the maximal plasma concentration.

Outcome measures

Measure	CSL112 (2 g) n=22 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=19 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=17 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants apoA-I	57.6 mg/dL Standard Deviation 19.5	164.3 mg/dL Standard Deviation 33.4	12.7 mg/dL Standard Deviation 19.5
Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants PC	59.0 mg/dL Standard Deviation 34.2	187.4 mg/dL Standard Deviation 49.9	9.1 mg/dL Standard Deviation 43.1

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Cmax is the maximal plasma concentration.

Outcome measures

Measure	CSL112 (2 g) n=13 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=10 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=13 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function apoA-I	40.9 mg/dL Standard Deviation 12.0	135.1 mg/dL Standard Deviation 22.8	7.8 mg/dL Standard Deviation 8.3
Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function PC	61.9 mg/dL Standard Deviation 21.0	184.9 mg/dL Standard Deviation 31.5	13.0 mg/dL Standard Deviation 16.5

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Cmax is the maximal plasma concentration.

Outcome measures

Measure	CSL112 (2 g) n=12 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=8 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=12 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function apoA-I	60.8 mg/dL Standard Deviation 19.2	149.0 mg/dL Standard Deviation 26.9	17.5 mg/dL Standard Deviation 20.3
Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function PC	45.8 mg/dL Standard Deviation 26.4	176.1 mg/dL Standard Deviation 54.0	20.1 mg/dL Standard Deviation 44.2

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Cmax is the maximal plasma concentration.

Outcome measures

Measure	CSL112 (2 g) n=11 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=10 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=5 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment apoA-I	44.6 mg/dL Standard Deviation 10.2	160.7 mg/dL Standard Deviation 37.0	5.2 mg/dL Standard Deviation 7.3
Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment PC	74.6 mg/dL Standard Deviation 14.7	211.3 mg/dL Standard Deviation 37.5	6.0 mg/dL Standard Deviation 10.8

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Cmax is the maximal plasma concentration.

Outcome measures

Measure	CSL112 (2 g) n=10 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=10 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=5 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment apoA-I	53.7 mg/dL Standard Deviation 20.1	169.7 mg/dL Standard Deviation 29.3	1.0 mg/dL Standard Deviation 12.1
Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment PC	74.8 mg/dL Standard Deviation 37.0	190.4 mg/dL Standard Deviation 46.7	-17.4 mg/dL Standard Deviation 28.9

SECONDARY outcome

Timeframe: Before and for 7 days after the first infusion

Population: PK/PD

Tmax is time to maximal plasma concentration

Outcome measures

Measure	CSL112 (2 g) n=24 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=21 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=18 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants apoA-I	2.23 hours Interval 1.7 to 236.9	2.17 hours Interval 2.0 to 4.0	46.8 hours Interval 0.0 to 216.3
Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants PC	2.23 hours Interval 1.7 to 8.4	2.17 hours Interval 2.0 to 4.0	5.29 hours Interval 0.0 to 188.9

SECONDARY outcome

Timeframe: Before and for 7 days after the fourth infusion

Population: PK/PD

Tmax is time to maximal plasma concentration

Outcome measures

Measure	CSL112 (2 g) n=22 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=19 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=17 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants apoA-I	2.13 hours Interval 2.0 to 23.5	2.25 hours Interval 2.0 to 4.2	119 hours Interval 0.0 to 332.9
Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants PC	2.17 hours Interval 2.0 to 53.1	2.25 hours Interval 2.0 to 4.2	46.93 hours Interval 0.0 to 187.3

SECONDARY outcome

Timeframe: Before and for 7 days after the first infusion

Population: PK/PD

Tmax is time to maximal plasma concentration

Outcome measures

Measure	CSL112 (2 g) n=13 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=10 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=13 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function apoA-I	2.25 hours Interval 1.7 to 236.9	2.17 hours Interval 2.0 to 3.4	96.1 hours Interval 0.0 to 216.3
Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function PC	2.22 hours Interval 1.7 to 8.4	2.17 hours Interval 2.0 to 3.4	8.1 hours Interval 0.0 to 188.9

SECONDARY outcome

Timeframe: Before and for 7 days after the fourth infusion

Population: PK/PD

Tmax is time to maximal plasma concentration

Outcome measures

Measure	CSL112 (2 g) n=12 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=8 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=12 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function apoA-I	2.13 hours Interval 2.1 to 3.5	2.17 hours Interval 2.0 to 2.4	119.3 hours Interval 0.0 to 332.9
Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function PC	2.17 hours Interval 2.1 to 53.1	2.17 hours Interval 2.0 to 2.4	29 hours Interval 0.0 to 187.3

SECONDARY outcome

Timeframe: Before and for 7 days after the first infusion

Population: PK/PD

Tmax is time to maximal plasma concentration

Outcome measures

Measure	CSL112 (2 g) n=11 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=10 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=5 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment apoA-I	2.18 hours Interval 2.1 to 3.4	2.22 hours Interval 2.1 to 4.0	0 hours Interval 0.0 to 117.9
Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment PC	2.28 hours Interval 2.1 to 5.0	2.22 hours Interval 2.1 to 4.0	0 hours Interval 0.0 to 5.3

SECONDARY outcome

Timeframe: Before and for 7 days after the fourth infusion

Population: PK/PD

Tmax is time to maximal plasma concentration

Outcome measures

Measure	CSL112 (2 g) n=10 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=10 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=5 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment PC	2.17 hours Interval 2.0 to 8.0	2.25 hours Interval 2.1 to 4.2	48.3 hours Interval 9.0 to 166.5
Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment apoA-I	2.17 hours Interval 2.0 to 23.5	2.25 hours Interval 2.1 to 4.2	72.5 hours Interval 0.0 to 166.5

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline [AUC0 - last]

Outcome measures

Measure	CSL112 (2 g) n=24 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=21 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=18 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants apoA-I	1703 mg•h/dL Standard Deviation 2149	4819 mg•h/dL Standard Deviation 2580	-766 mg•h/dL Standard Deviation 2248
Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants PC	-66.12 mg•h/dL Standard Deviation 3653	869 mg•h/dL Standard Deviation 3796	-2096 mg•h/dL Standard Deviation 3372

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline [AUC0 - last]

Outcome measures

Measure	CSL112 (2 g) n=22 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=19 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=17 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants apoA-I	4579 mg•h/dL Standard Deviation 2705	8985 mg•h/dL Standard Deviation 4263	747 mg•h/dL Standard Deviation 3226
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants PC	70.7 mg•h/dL Standard Deviation 5327	2499 mg•h/dL Standard Deviation 7662	-2185 mg•h/dL Standard Deviation 5189

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline [AUC0 - last]

Outcome measures

Measure	CSL112 (2 g) n=13 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=10 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=13 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function apoA-I	1278 mg•h/dL Standard Deviation 1742	3762 mg•h/dL Standard Deviation 2367	-516 mg•h/dL Standard Deviation 2091
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function PC	-1382 mg•h/dL Standard Deviation 2853	-137 mg•h/dL Standard Deviation 4057	-1337 mg•h/dL Standard Deviation 2590

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline [AUC0 - last]

Outcome measures

Measure	CSL112 (2 g) n=12 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=8 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=12 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function apoA-I	4513 mg•h/dL Standard Deviation 2701	8609 mg•h/dL Standard Deviation 4500	1632 mg•h/dL Standard Deviation 3235
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function PC	-2130 mg•h/dL Standard Deviation 4691	3609 mg•h/dL Standard Deviation 10232	-542 mg•h/dL Standard Deviation 4480

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline [AUC0 - last]

Outcome measures

Measure	CSL112 (2 g) n=11 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=10 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=5 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment apoA-I	2205 mg•h/dL Standard Deviation 2543	5917 mg•h/dL Standard Deviation 2568	-1416 mg•h/dL Standard Deviation 2763
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment PC	1489 mg•h/dL Standard Deviation 4003	1828 mg•h/dL Standard Deviation 3661	-4068 mg•h/dL Standard Deviation 4634

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline [AUC0 - last]

Outcome measures

Measure	CSL112 (2 g) n=10 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=10 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=5 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment apoA-I	4659 mg•h/dL Standard Deviation 2854	8786 mg•h/dL Standard Deviation 4201	-1376 mg•h/dL Standard Deviation 2205
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment PC	2712 mg•h/dL Standard Deviation 5010	1541 mg•h/dL Standard Deviation 5815	-6128 mg•h/dL Standard Deviation 4998

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

AUC from baseline to time point t (AUC0-t)

Outcome measures

Measure	CSL112 (2 g) n=24 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=21 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=18 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants apoA-I (0-24h)	496 mg•h/dL Standard Deviation 212	1929 mg•h/dL Standard Deviation 557	-168 mg•h/dL Standard Deviation 158
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants apoA-I (0-48h)	731 mg•h/dL Standard Deviation 447	2903 mg•h/dL Standard Deviation 944	-331 mg•h/dL Standard Deviation 375
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants apoA-I (0-72h)	880 mg•h/dL Standard Deviation 726	3516 mg•h/dL Standard Deviation 1248	-439 mg•h/dL Standard Deviation 632
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants apoA-I (0-96h)	1006 mg•h/dL Standard Deviation 1104	3943 mg•h/dL Standard Deviation 1581	-541 mg•h/dL Standard Deviation 940
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants apoA-I (0-168h)	1009 mg•h/dL Standard Deviation 1761	4734 mg•h/dL Standard Deviation 2382	-452 mg•h/dL Standard Deviation 1498
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants PC (0-24h)	508 mg•h/dL Standard Deviation 349	1545 mg•h/dL Standard Deviation 552	-92 mg•h/dL Standard Deviation 229
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants PC (0-48h)	466 mg•h/dL Standard Deviation 744	1627 mg•h/dL Standard Deviation 872	-315 mg•h/dL Standard Deviation 522
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants PC (0-72h)	418 mg•h/dL Standard Deviation 1251	1713 mg•h/dL Standard Deviation 1209	-549 mg•h/dL Standard Deviation 886
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants PC (0-96h)	389 mg•h/dL Standard Deviation 1841	1712 mg•h/dL Standard Deviation 1694	-780 mg•h/dL Standard Deviation 1346
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants PC (0-168h)	-405 mg•h/dL Standard Deviation 3636	1273 mg•h/dL Standard Deviation 2764	-1494 mg•h/dL Standard Deviation 2501

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

AUC from baseline to time point t (AUC0-t)

Outcome measures

Measure	CSL112 (2 g) n=22 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=19 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=17 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants apoA-I (0-24h)	881 mg•h/dL Standard Deviation 422	2392 mg•h/dL Standard Deviation 655	-57 mg•h/dL Standard Deviation 377
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants apoA-I (0-48h)	1593 mg•h/dL Standard Deviation 798	3913 mg•h/dL Standard Deviation 1235	-55 mg•h/dL Standard Deviation 759
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants apoA-I (0-72h)	2195 mg•h/dL Standard Deviation 1177	5050 mg•h/dL Standard Deviation 1794	-6 mg•h/dL Standard Deviation 1160
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants apoA-I (0-96h)	2741 mg•h/dL Standard Deviation 1526	6000 mg•h/dL Standard Deviation 2292	90 mg•h/dL Standard Deviation 1590
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants apoA-I (0-168h)	3997 mg•h/dL Standard Deviation 2655	8865 mg•h/dL Standard Deviation 3200	1635 mg•h/dL Standard Deviation 3540
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants PC (0-24h)	462 mg•h/dL Standard Deviation 681	1564 mg•h/dL Standard Deviation 1051	-488 mg•h/dL Standard Deviation 772
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants PC (0-48h)	472 mg•h/dL Standard Deviation 1293	1765 mg•h/dL Standard Deviation 1948	-902 mg•h/dL Standard Deviation 1433
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants PC (0-72h)	509 mg•h/dL Standard Deviation 1989	1899 mg•h/dL Standard Deviation 2823	-1173 mg•h/dL Standard Deviation 2168
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants PC (0-96h)	518 mg•h/dL Standard Deviation 2679	1951 mg•h/dL Standard Deviation 3681	-1417 mg•h/dL Standard Deviation 2894
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants PC (0-168h)	-625 mg•h/dL Standard Deviation 4963	2655 mg•h/dL Standard Deviation 6024	-442 mg•h/dL Standard Deviation 6319

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

AUC from baseline to time point t (AUC0-t)

Outcome measures

Measure	CSL112 (2 g) n=13 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=10 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=13 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function apoA-I (0-24h)	418 mg•h/dL Standard Deviation 117	1653 mg•h/dL Standard Deviation 496	-149 mg•h/dL Standard Deviation 123
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function apoA-I (0-48h)	547 mg•h/dL Standard Deviation 204	2521 mg•h/dL Standard Deviation 955	-316 mg•h/dL Standard Deviation 332
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function apoA-I (0-72h)	628 mg•h/dL Standard Deviation 337	3064 mg•h/dL Standard Deviation 1280	-435 mg•h/dL Standard Deviation 579
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function apoA-I (0-96h)	692 mg•h/dL Standard Deviation 554	3342 mg•h/dL Standard Deviation 1642	-528 mg•h/dL Standard Deviation 883
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function apoA-I (0-168h)	821 mg•h/dL Standard Deviation 1387	3780 mg•h/dL Standard Deviation 2353	-275 mg•h/dL Standard Deviation 1461
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function PC (0-24h)	364 mg•h/dL Standard Deviation 245	1347 mg•h/dL Standard Deviation 661	-46 mg•h/dL Standard Deviation 160
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function PC (0-48h)	145 mg•h/dL Standard Deviation 536	1294 mg•h/dL Standard Deviation 1025	-235 mg•h/dL Standard Deviation 441
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function PC (0-72h)	-38 mg•h/dL Standard Deviation 946	1325 mg•h/dL Standard Deviation 1421	-426 mg•h/dL Standard Deviation 759
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function PC (0-96h)	-256 mg•h/dL Standard Deviation 1415	1218 mg•h/dL Standard Deviation 2005	-569 mg•h/dL Standard Deviation 1162
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function PC (0-168h)	-1511 mg•h/dL Standard Deviation 3053	437 mg•h/dL Standard Deviation 2061	-1089 mg•h/dL Standard Deviation 2188

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

AUC from baseline to time point t (AUC0-t)

Outcome measures

Measure	CSL112 (2 g) n=12 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=8 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=12 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function apoA-I (0-168h)	3811 mg•h/dL Standard Deviation 2706	8342 mg•h/dL Standard Deviation 2549	2486 mg•h/dL Standard Deviation 2804
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function PC (0-24h)	189 mg•h/dL Standard Deviation 483	1524 mg•h/dL Standard Deviation 1388	-295 mg•h/dL Standard Deviation 819
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function PC (0-48h)	-59 mg•h/dL Standard Deviation 952	1796 mg•h/dL Standard Deviation 2613	-523 mg•h/dL Standard Deviation 1446
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function PC (0-72h)	-306 mg•h/dL Standard Deviation 1544	2000 mg•h/dL Standard Deviation 3773	-605 mg•h/dL Standard Deviation 2133
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function PC (0-96h)	-573 mg•h/dL Standard Deviation 2204	2078 mg•h/dL Standard Deviation 4905	-633 mg•h/dL Standard Deviation 2772
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function PC (0-168h)	-3853 mg•h/dL Standard Deviation 3242	4584 mg•h/dL Standard Deviation 7822	1253 mg•h/dL Standard Deviation 4446
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function apoA-I (0-24h)	929 mg•h/dL Standard Deviation 396	2098 mg•h/dL Standard Deviation 463	20 mg•h/dL Standard Deviation 417
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function apoA-I (0-48h)	1668 mg•h/dL Standard Deviation 753	3459 mg•h/dL Standard Deviation 1001	105 mg•h/dL Standard Deviation 820
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function apoA-I (0-72h)	2252 mg•h/dL Standard Deviation 1116	4497 mg•h/dL Standard Deviation 1478	249 mg•h/dL Standard Deviation 1232
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function apoA-I (0-96h)	2769 mg•h/dL Standard Deviation 1473	5360 mg•h/dL Standard Deviation 1909	459 mg•h/dL Standard Deviation 1666

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

AUC from baseline to time point t (AUC0-t)

Outcome measures

Measure	CSL112 (2 g) n=11 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=10 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=5 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment apoA-I (0-24h)	589 mg•h/dL Standard Deviation 263	2219 mg•h/dL Standard Deviation 515	-218 mg•h/dL Standard Deviation 238
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment apoA-I (0-48h)	949 mg•h/dL Standard Deviation 560	3308 mg•h/dL Standard Deviation 847	-370 mg•h/dL Standard Deviation 514
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment apoA-I (0-72h)	1179 mg•h/dL Standard Deviation 946	3998 mg•h/dL Standard Deviation 1152	-451 mg•h/dL Standard Deviation 834
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment apoA-I (0-96h)	1376 mg•h/dL Standard Deviation 1468	4517 mg•h/dL Standard Deviation 1465	-576 mg•h/dL Standard Deviation 1188
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment apoA-I (0-168h)	1196 mg•h/dL Standard Deviation 2155	5624 mg•h/dL Standard Deviation 2293	-865 mg•h/dL Standard Deviation 1824
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment PC (0-24h)	678 mg•h/dL Standard Deviation 386	1777 mg•h/dL Standard Deviation 353	-212 mg•h/dL Standard Deviation 348
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment PC (0-48h)	845 mg•h/dL Standard Deviation 797	1968 mg•h/dL Standard Deviation 623	-523 mg•h/dL Standard Deviation 705
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment PC (0-72h)	956 mg•h/dL Standard Deviation 1393	2093 mg•h/dL Standard Deviation 950	-871 mg•h/dL Standard Deviation 1196
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment PC (0-96h)	1227 mg•h/dL Standard Deviation 2058	2194 mg•h/dL Standard Deviation 1351	-1329 mg•h/dL Standard Deviation 1769
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment PC (0-168h)	1018 mg•h/dL Standard Deviation 4052	2004 mg•h/dL Standard Deviation 3214	2203 mg•h/dL Standard Deviation 3197

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

AUC from baseline to time point t (AUC0-t)

Outcome measures

Measure	CSL112 (2 g) n=10 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=10 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=5 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment apoA-I (0-24h)	823 mg•h/dL Standard Deviation 466	2469 mg•h/dL Standard Deviation 573	-243 mg•h/dL Standard Deviation 170
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment apoA-I (0-48h)	1503 mg•h/dL Standard Deviation 881	4049 mg•h/dL Standard Deviation 1221	-440 mg•h/dL Standard Deviation 436
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment apoA-I (0-72h)	2128 mg•h/dL Standard Deviation 1304	5226 mg•h/dL Standard Deviation 1910	-617 mg•h/dL Standard Deviation 741
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment apoA-I (0-96h)	2707 mg•h/dL Standard Deviation 1669	6212 mg•h/dL Standard Deviation 2503	-796 mg•h/dL Standard Deviation 1045
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment apoA-I (0-168h)	4229 mg•h/dL Standard Deviation 2754	8840 mg•h/dL Standard Deviation 3678	-4322 mg•h/dL Standard Deviation 0
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment PC (0-24h)	789 mg•h/dL Standard Deviation 760	1518 mg•h/dL Standard Deviation 799	-950 mg•h/dL Standard Deviation 405
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment PC (0-48h)	1110 mg•h/dL Standard Deviation 1402	1650 mg•h/dL Standard Deviation 1474	-1810 mg•h/dL Standard Deviation 1001
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment PC (0-72h)	1487 mg•h/dL Standard Deviation 2090	1726 mg•h/dL Standard Deviation 2176	-2536 mg•h/dL Standard Deviation 1731
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment PC (0-96h)	1826 mg•h/dL Standard Deviation 2706	1751 mg•h/dL Standard Deviation 2867	-3297 mg•h/dL Standard Deviation 2471
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment PC (0-168h)	2603 mg•h/dL Standard Deviation 4295	1316 mg•h/dL Standard Deviation 4998	-12308 mg•h/dL Standard Deviation 0

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

AUC0-∞ is plasma area under the curve (AUC0-infinity)

Outcome measures

Measure	CSL112 (2 g) n=6 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=16 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=1 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for All Participants apoA-I	1425 mg•h/dL Standard Deviation 1297	6090 mg•h/dL Standard Deviation 3642	—
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for All Participants PC	1850 mg•h/dL Standard Deviation 3120	1678 mg•h/dL Standard Deviation 651	6979 mg•h/dL Standard Deviation 0

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

AUC0-∞ is plasma area under the curve (AUC0-infinity)

Outcome measures

Measure	CSL112 (2 g) n=10 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=15 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=1 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for All Participants apoA-I	15540 mg•h/dL Standard Deviation 19437	13570 mg•h/dL Standard Deviation 6965	4615 mg•h/dL Standard Deviation 0
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for All Participants PC	2015 mg•h/dL Standard Deviation 2855	12863 mg•h/dL Standard Deviation 16731	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

AUC0-∞ is plasma area under the curve (AUC0-infinity)

Outcome measures

Measure	CSL112 (2 g) n=3 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=8 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Normal Renal Function apoA-I	589 mg•h/dL Standard Deviation 17	4505 mg•h/dL Standard Deviation 2528	—
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Normal Renal Function PC	490 mg•h/dL Standard Deviation 1540	1596 mg•h/dL Standard Deviation 785	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

AUC0-∞ is plasma area under the curve (AUC0-infinity)

Outcome measures

Measure	CSL112 (2 g) n=7 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=5 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=1 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function apoA-I	17079 mg•h/dL Standard Deviation 23224	12422 mg•h/dL Standard Deviation 7399	4615 mg•h/dL Standard Deviation 0
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function PC	638 mg•h/dL Standard Deviation 566	16142 mg•h/dL Standard Deviation 17777	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

AUC0-∞ is plasma area under the curve (AUC0-infinity)

Outcome measures

Measure	CSL112 (2 g) n=4 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=7 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=1 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment apoA-I	1842 mg•h/dL Standard Deviation 1451	8032 mg•h/dL Standard Deviation 4220	—
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment PC	3210 mg•h/dL Standard Deviation 4052	1761 mg•h/dL Standard Deviation 566	6979 mg•h/dL Standard Deviation 0

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

AUC0-∞ is plasma area under the curve (AUC0-infinity)

Outcome measures

Measure	CSL112 (2 g) n=3 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=9 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment apoA-I	11951 mg•h/dL Standard Deviation 7374	13157 mg•h/dL Standard Deviation 6734	—
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment PC	4769 mg•h/dL Standard Deviation 4128	12827 mg•h/dL Standard Deviation 18453	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=6 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=16 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=1 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for All Participants apoA-I	46.4 hours Standard Deviation 33.1	53.9 hours Standard Deviation 38.7	—
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for All Participants PC	32.9 hours Standard Deviation 29.6	9.7 hours Standard Deviation 7.2	241.2 hours Standard Deviation 0

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=10 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=15 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=1 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for All Participants apoA-I	269.1 hours Standard Deviation 292	103.6 hours Standard Deviation 61.1	145 hours Standard Deviation 0
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for All Participants PC	21.5 hours Standard Deviation 20.6	156.3 hours Standard Deviation 245.8	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=3 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=8 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Normal Renal Function apoA-I	7.5 hours Standard Deviation 1.7	41.4 hours Standard Deviation 24.1	—
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Normal Renal Function PC	34 hours Standard Deviation 27.7	12.3 hours Standard Deviation 8.9	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=7 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=5 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=1 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function apoA-I	271.6 hours Standard Deviation 317.4	96.5 hours Standard Deviation 47.3	145 hours Standard Deviation 0
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function PC	9.1 hours Standard Deviation 9.3	121.1 hours Standard Deviation 102.7	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=4 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=7 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=1 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment apoA-I	65.9 hours Standard Deviation 17.5	66.4 hours Standard Deviation 51.4	—
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment PC	31.8 hours Standard Deviation 37.7	7.1 hours Standard Deviation 4.4	241.2 hours Standard Deviation 0

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=3 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=9 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment apoA-I	263.1 hours Standard Deviation 285.4	99.2 hours Standard Deviation 68.2	—
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment PC	46.3 hours Standard Deviation 2.2	185.6 hours Standard Deviation 306.5	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=6 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=16 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for All Participants apoA-I	0.29 L/h Standard Deviation 0.27	0.15 L/h Standard Deviation 0.13	—
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for All Participants PC	0.32 L/h Standard Deviation 0.26	0.61 L/h Standard Deviation 0.26	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=17 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=16 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for All Participants apoA-I	0.09 L/h Standard Deviation 0.1	0.07 L/h Standard Deviation 0.02	—
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for All Participants PC	0.11 L/h Standard Deviation 0.09	0.57 L/h Standard Deviation 1.12	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=2 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=8 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Normal Renal Function apoA-I	0.33 L/h Standard Deviation 0.01	0.19 L/h Standard Deviation 0.17	—
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Normal Renal Function PC	0.41 L/h Standard Deviation 0.38	0.68 L/h Standard Deviation 0.35	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=10 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=6 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function apoA-I	0.11 L/h Standard Deviation 0.12	0.08 L/h Standard Deviation 0.02	—
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function PC	0.24 L/h Standard Deviation 0	0.19 L/h Standard Deviation 0.12	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=4 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=7 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment apoA-I	0.27 L/h Standard Deviation 0.35	0.09 L/h Standard Deviation 0.05	—
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment PC	0.26 L/h Standard Deviation 0.23	0.54 L/h Standard Deviation 0.13	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=7 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=9 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment apoA-I	0.05 L/h Standard Deviation 0.02	0.08 L/h Standard Deviation 0.03	—
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment PC	0.08 L/h Standard Deviation 0.07	1.01 L/h Standard Deviation 1.63	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=6 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=16 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Volume of Distribution at Steady State (Vss) for apoA-I and PC After First Infusion for All Participants apoA-I	33.4 Liters Standard Deviation 64.7	7.4 Liters Standard Deviation 3.1	—
Change From Baseline in Plasma Volume of Distribution at Steady State (Vss) for apoA-I and PC After First Infusion for All Participants PC	6.1 Liters Standard Deviation 4.4	14.4 Liters Standard Deviation 33.3	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=10 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=15 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for All Participants apoA-I	18.7 Liters Standard Deviation 16.6	9.4 Liters Standard Deviation 4.7	—
Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for All Participants PC	10.7 Liters Standard Deviation 7.5	58.3 Liters Standard Deviation 94.9	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=2 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=8 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Normal Renal Function apoA-I	3.8 Liters Standard Deviation 0.9	8.1 Liters Standard Deviation 3.8	—
Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Normal Renal Function PC	8.3 Liters Standard Deviation 7.7	24.7 Liters Standard Deviation 47.2	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=7 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=5 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function apoA-I	18.7 Liters Standard Deviation 16.1	9.4 Liters Standard Deviation 2.5	—
Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function PC	11.4 Liters Standard Deviation 8.3	17 Liters Standard Deviation 10.3	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after first infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=4 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=7 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment apoA-I	48.2 Liters Standard Deviation 78.1	6.4 Liters Standard Deviation 2.3	—
Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment PC	4.7 Liters Standard Deviation 1.3	4 Liters Standard Deviation 1.5	—

SECONDARY outcome

Timeframe: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion

Population: PK/PD

Outcome measures

Measure	CSL112 (2 g) n=3 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=9 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment apoA-I	18.7 Liters Standard Deviation 21.3	9.4 Liters Standard Deviation 5.9	—
Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment PC	9.3 Liters Standard Deviation 8.2	83.1 Liters Standard Deviation 114	—

SECONDARY outcome

Timeframe: From the start of first infusion, up to approximately Day 382

Population: SP

The overall percentage of subjects:

• with adverse events (AEs), including local tolerability events, that begin during or within 1 hour of an infusion; or
• with AEs considered to be causally related to the test product; or
• who experience an AE for which the incidence rate 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.

Outcome measures

Measure	CSL112 (2 g) n=415 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=416 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=413 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Percent of Participants With the Occurrence of Suspected Adverse Drug Reactions	31.8 percentage of participants	28.4 percentage of participants	23.5 percentage of participants

SECONDARY outcome

Timeframe: From the start of first infusion, up to approximately Day 382

Population: SP

Outcome measures

Measure	CSL112 (2 g) n=415 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=416 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=413 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Percent of Participants With Any Adverse Event (AE)	50.6 percentage of participants	51.4 percentage of participants	49.6 percentage of participants

SECONDARY outcome

Timeframe: From the start of first infusion, up to approximately Day 112

Population: SP

The number of subjects who experience bleeding events as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al, 2011)

Outcome measures

Measure	CSL112 (2 g) n=415 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=416 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=413 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Percent of Participants Who Experience Bleeding Events	9.2 percentage of participants	9.1 percentage of participants	12.3 percentage of participants

SECONDARY outcome

Timeframe: Before first infusion, up to approximately Day 112

Population: SP

Outcome measures

Measure	CSL112 (2 g) n=377 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=389 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=380 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Change From Baseline in Serum Antibodies to CSL112 and apoA-I Anti-CSL112 antibody	0 Titer Standard Deviation 0.14	0 Titer Standard Deviation 0.2	0 Titer Standard Deviation 0.2
Change From Baseline in Serum Antibodies to CSL112 and apoA-I Anti-apoA-I antibody	0 Titer Standard Deviation 0.09	0 Titer Standard Deviation 0.14	0 Titer Standard Deviation 0.1

SECONDARY outcome

Timeframe: Study Day 112

Population: Serology population are a random subset of participants that was selected and had their samples tested for the presence of parvovirus B19.

Outcome measures

Measure	CSL112 (2 g) n=60 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=60 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=60 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19 IgG	40 participants	48 participants	44 participants
Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19 IgM	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Study Day 112

Population: Serology population

Outcome measures

Measure	CSL112 (2 g) n=60 Participants CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	CSL112 (6 g) n=60 Participants CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks. CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.	Placebo n=60 Participants Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion. Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
Number of Participants With Parvovirus B19 DNA in Serum Not detected	57 participants	60 participants	59 participants
Number of Participants With Parvovirus B19 DNA in Serum < 101 IU/mL	1 participants	0 participants	1 participants
Number of Participants With Parvovirus B19 DNA in Serum Missing	2 participants	0 participants	0 participants

Adverse Events

Safety Lead-in [CSL112 (2 g)]

Serious events: 1 serious events

Other events: 2 other events

Deaths: 1 deaths

CSL112 (2 g)

Serious events: 66 serious events

Other events: 15 other events

Deaths: 5 deaths

CSL112 (6 g)

Serious events: 54 serious events

Other events: 23 other events

Deaths: 4 deaths

Placebo

Serious events: 55 serious events

Other events: 9 other events

Deaths: 1 deaths

Serious adverse events

Measure	Safety Lead-in [CSL112 (2 g)] n=9 participants at risk In the safety lead-in, a small number of subjects (evenly stratified between subjects with normal renal function or mild renal impairment) were administered a single, 2 g infusion of CSL112.	CSL112 (2 g) n=415 participants at risk CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks.	CSL112 (6 g) n=416 participants at risk CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks.	Placebo n=413 participants at risk Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion.
Vascular disorders Deep vein thrombosis	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Vascular disorders Hypertension	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Vascular disorders Hypotension	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 2 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Vascular disorders Shock haemorrhagic	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Vascular disorders Arterial haemorrhage	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Vascular disorders Hypertensive crisis	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Vascular disorders Peripheral artery occlusion	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.48% 2/413 • Number of events 2 • Up to 382 days for each participant
Vascular disorders Thrombosis	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal neoplasm	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
General disorders Chest pain	0.00% 0/9 • Up to 382 days for each participant	2.2% 9/415 • Number of events 10 • Up to 382 days for each participant	0.96% 4/416 • Number of events 4 • Up to 382 days for each participant	1.2% 5/413 • Number of events 5 • Up to 382 days for each participant
General disorders Non-cardiac chest pain	0.00% 0/9 • Up to 382 days for each participant	0.48% 2/415 • Number of events 2 • Up to 382 days for each participant	0.96% 4/416 • Number of events 4 • Up to 382 days for each participant	0.97% 4/413 • Number of events 6 • Up to 382 days for each participant
General disorders Asthenia	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
General disorders Multiple organ dysfunction syndrome	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
General disorders Pyrexia	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
General disorders Vascular stent restenosis	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.48% 2/413 • Number of events 3 • Up to 382 days for each participant
General disorders Vascular stent thrombosis	11.1% 1/9 • Number of events 1 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Psychiatric disorders Anxiety	0.00% 0/9 • Up to 382 days for each participant	0.48% 2/415 • Number of events 2 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Psychiatric disorders Depressed mood	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Psychiatric disorders Depression	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Psychiatric disorders Mental disorder	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Reproductive system and breast disorders Ovarian cyst	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Injury, poisoning and procedural complications Contusion	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Injury, poisoning and procedural complications Coronary artery restenosis	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Injury, poisoning and procedural complications Fall	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Injury, poisoning and procedural complications Pubis fracture	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Injury, poisoning and procedural complications Rib fracture	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 2 • Up to 382 days for each participant
Investigations Ejection fraction decreased	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Angina pectoris	0.00% 0/9 • Up to 382 days for each participant	1.2% 5/415 • Number of events 5 • Up to 382 days for each participant	1.4% 6/416 • Number of events 7 • Up to 382 days for each participant	1.2% 5/413 • Number of events 6 • Up to 382 days for each participant
Cardiac disorders Angina unstable	0.00% 0/9 • Up to 382 days for each participant	1.4% 6/415 • Number of events 6 • Up to 382 days for each participant	0.72% 3/416 • Number of events 3 • Up to 382 days for each participant	0.97% 4/413 • Number of events 5 • Up to 382 days for each participant
Cardiac disorders Atrial fibrillation	0.00% 0/9 • Up to 382 days for each participant	0.72% 3/415 • Number of events 3 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Cardiac disorders Coronary artery stenosis	0.00% 0/9 • Up to 382 days for each participant	0.72% 3/415 • Number of events 4 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Cardiac disorders Myocardial infarction	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.72% 3/416 • Number of events 3 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Ventricular tachycardia	0.00% 0/9 • Up to 382 days for each participant	0.72% 3/415 • Number of events 3 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Cardiac disorders Cardiac failure congestive	0.00% 0/9 • Up to 382 days for each participant	0.48% 2/415 • Number of events 4 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.48% 2/413 • Number of events 2 • Up to 382 days for each participant
Cardiac disorders Acute coronary syndrome	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Atrial tachycardia	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Bradycardia	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Cardiac aneurysm	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Cardiac arrest	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Cardiac asthma	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Cardiac ventricular thrombosis	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Intracardiac thrombus	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Myocardial ischaemia	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Palpitations	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Cardiac disorders Prinzmetal angina	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 2 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Sinus bradycardia	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Ventricular fibrillation	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Ventricular septal defect acquired	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Cardiac failure acute	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Cardiac disorders Cardiomyopathy	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Cardiac disorders Coronary artery dissection	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Cardiac disorders Coronary artery occlusion	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Cardiac disorders Mitral valve incompetence	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Cardiac disorders Supraventricular tachycardia	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Cardiac disorders Cardiac failure	11.1% 1/9 • Number of events 1 • Up to 382 days for each participant	0.72% 3/415 • Number of events 3 • Up to 382 days for each participant	0.72% 3/416 • Number of events 4 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Congenital, familial and genetic disorders Arteriovenous malformation	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	11.1% 1/9 • Number of events 1 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/9 • Up to 382 days for each participant	0.48% 2/415 • Number of events 2 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Pharyngeal oedema	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/9 • Up to 382 days for each participant	0.48% 2/415 • Number of events 2 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Nervous system disorders Syncope	0.00% 0/9 • Up to 382 days for each participant	0.48% 2/415 • Number of events 2 • Up to 382 days for each participant	0.48% 2/416 • Number of events 2 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Nervous system disorders Paraesthesia	0.00% 0/9 • Up to 382 days for each participant	0.72% 3/415 • Number of events 4 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Nervous system disorders Carotid artery stenosis	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Nervous system disorders Basal ganglia haemorrhage	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Nervous system disorders Carotid artery disease	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Nervous system disorders Cerebrovascular accident	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 2 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Nervous system disorders Diabetic neuropathy	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Nervous system disorders Hypoxic-ischaemic encephalopathy	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Nervous system disorders Lumbar radiculopathy	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Nervous system disorders Sciatica	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Nervous system disorders Cerebral ischaemia	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Nervous system disorders Cluster headache	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Nervous system disorders Dizziness	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Nervous system disorders Presyncope	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Eye disorders Visual impairment	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Ear and labyrinth disorders Vertigo	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.48% 2/416 • Number of events 3 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Gastritis	0.00% 0/9 • Up to 382 days for each participant	0.48% 2/415 • Number of events 2 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Gastrointestinal disorders Abdominal pain	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Abdominal pain upper	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Chronic gastritis	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Crohn's disease	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Diarrhoea	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 3 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Mechanical ileus	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Nausea	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Pancreatitis acute	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Retroperitoneal haematoma	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Vomiting	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 2 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Gastrointestinal disorders Intestinal haemorrhage	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Gastrointestinal disorders Pancreatitis	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Renal and urinary disorders Acute kidney injury	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Renal and urinary disorders Postrenal failure	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Hepatobiliary disorders Cholelithiasis	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Hepatobiliary disorders Cholestasis	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Musculoskeletal and connective tissue disorders Fasciitis	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Musculoskeletal and connective tissue disorders Polymyalgia rheumatica	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Endocrine disorders Hyperthyroidism	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Infections and infestations Bronchitis	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Infections and infestations Urinary tract infection	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Infections and infestations Clostridial infection	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Infections and infestations Clostridium difficile colitis	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Infections and infestations Escherichia urinary tract infection	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.24% 1/416 • Number of events 1 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Infections and infestations Gastroenteritis	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Infections and infestations Haematoma infection	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Infections and infestations Oral fungal infection	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Infections and infestations Pneumonia	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 2 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.48% 2/413 • Number of events 2 • Up to 382 days for each participant
Infections and infestations Sepsis	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Infections and infestations Septic shock	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Infections and infestations Staphylococcal infection	0.00% 0/9 • Up to 382 days for each participant	0.24% 1/415 • Number of events 1 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Infections and infestations Nasopharyngitis	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Infections and infestations Postoperative abscess	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Infections and infestations Soft tissue infection	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant
Infections and infestations Urosepsis	0.00% 0/9 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.24% 1/413 • Number of events 1 • Up to 382 days for each participant

Other adverse events

Measure	Safety Lead-in [CSL112 (2 g)] n=9 participants at risk In the safety lead-in, a small number of subjects (evenly stratified between subjects with normal renal function or mild renal impairment) were administered a single, 2 g infusion of CSL112.	CSL112 (2 g) n=415 participants at risk CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks.	CSL112 (6 g) n=416 participants at risk CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks.	Placebo n=413 participants at risk Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion.
Vascular disorders Hypertension	11.1% 1/9 • Number of events 1 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Angina pectoris	11.1% 1/9 • Number of events 1 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Cardiac disorders Extrasystoles	11.1% 1/9 • Number of events 1 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/9 • Up to 382 days for each participant	3.6% 15/415 • Number of events 19 • Up to 382 days for each participant	5.5% 23/416 • Number of events 24 • Up to 382 days for each participant	2.2% 9/413 • Number of events 10 • Up to 382 days for each participant
Nervous system disorders Syncope	11.1% 1/9 • Number of events 1 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant
Skin and subcutaneous tissue disorders Skin exfoliation	11.1% 1/9 • Number of events 1 • Up to 382 days for each participant	0.00% 0/415 • Up to 382 days for each participant	0.00% 0/416 • Up to 382 days for each participant	0.00% 0/413 • Up to 382 days for each participant

Additional Information

Trial Registration Coordinator

CSLBehring

Phone: 610-878-4000

Email: clinicaltrials@cslbehring.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place