Trial Outcomes & Findings for Study to Evaluate the Efficacy of ASP1128 (MA-0217) in Subjects at Risk for Acute Kidney Injury (AKI) Following Coronary Artery Bypass Graft (CABG) and/or Valve Surgery (NCT NCT03941483)

NCT ID: NCT03941483

Last Updated: 2024-12-04

Results Overview

Development of AKI was based on SCr criteria from the kidney disease improving global outcomes (KDIGO) guideline (i.e., increase in SCr ≥ 0.3 milligram per deciliter (mg/dL) \[≥ 26.5 micromoles per liter {μmol/L}\] within any 48 hours or increase in SCr to ≥ 1.5 times baseline within 72 hours after end of surgery \[T0\]). Percentage of participants who developed AKI-SCr72h were reported.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 351 participants
• Primary outcome timeframe: From end of surgery up to 72 hrs
• Results posted on: 2024-12-04

Participant Flow

A total of 351 were enrolled in the study, of which 151 participants were randomized and 150 received treatment in double-blind treatment period, and the rest of 200 were enrolled in observational cohort.

Participants who underwent coronary artery bypass graft (CABG) and/or valve surgery and had a moderate or high risk for developing acute kidney injury (AKI) based on serum creatinine (SCr) kidney disease improving global outcomes (KDIGO) criteria (AKI-SCr) postsurgery were enrolled in the study. Randomization was stratified for estimated glomerular filtration rate (eGFR) at < 45 and ≥ 45 milliliter per minute (mL/min) per 1.73 square meter (m^2).

Participant milestones

Measure	ASP1128 Participants received ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Placebo Participants received placebo matched to ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Observational Cohort Participant with postoperative negative NephroCheck® (NC) (AKIRisk score was ≤ 0.3 nanogram per milliliter (ng/mL)\^2/1000 at all assessments between 2 to 22 hours after time point 0 (T0) were followed up for 90 days in observational cohort. Participants did not receive any intervention.
Overall Study STARTED	70	81	200
Overall Study Treated	69	81	0
Overall Study COMPLETED	61	71	185
Overall Study NOT COMPLETED	9	10	15

Reasons for withdrawal

Measure	ASP1128 Participants received ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Placebo Participants received placebo matched to ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Observational Cohort Participant with postoperative negative NephroCheck® (NC) (AKIRisk score was ≤ 0.3 nanogram per milliliter (ng/mL)\^2/1000 at all assessments between 2 to 22 hours after time point 0 (T0) were followed up for 90 days in observational cohort. Participants did not receive any intervention.
Overall Study Miscellaneous	2	3	0
Overall Study Study Terminated by Sponsor	1	0	0
Overall Study Withdrawal by Subject	1	4	1
Overall Study Lost to Follow-up	2	1	8
Overall Study Death	3	2	6

Baseline Characteristics

eGFR was meant to be collected for randomized participants (ASP1128 and Placebo) only.

Baseline characteristics by cohort

Measure	ASP1128 n=69 Participants Participants received ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Placebo n=81 Participants Participants received placebo matched to ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Observational Cohort n=200 Participants Participant with postoperative negative NephroCheck® (NC) (AKIRisk score was ≤ 0.3 ng/mL\^2/1000 at all assessments between 2 to 22 hours after time point 0 (T0) were followed up for 90 days in observational cohort. Participants did not receive any intervention.	Total n=350 Participants Total of all reporting groups
Age, Continuous	68.0 Years STANDARD_DEVIATION 8.3 • n=69 Participants	68.7 Years STANDARD_DEVIATION 9.4 • n=81 Participants	69.4 Years STANDARD_DEVIATION 8.8 • n=200 Participants	69 Years STANDARD_DEVIATION 8.8 • n=350 Participants
Sex: Female, Male Female	16 Participants n=69 Participants	7 Participants n=81 Participants	65 Participants n=200 Participants	88 Participants n=350 Participants
Sex: Female, Male Male	53 Participants n=69 Participants	74 Participants n=81 Participants	135 Participants n=200 Participants	262 Participants n=350 Participants
Race/Ethnicity, Customized Race · White	65 Participants n=69 Participants	79 Participants n=81 Participants	182 Participants n=200 Participants	326 Participants n=350 Participants
Race/Ethnicity, Customized Race · Black or African American	4 Participants n=69 Participants	1 Participants n=81 Participants	16 Participants n=200 Participants	21 Participants n=350 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=69 Participants	0 Participants n=81 Participants	0 Participants n=200 Participants	0 Participants n=350 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=69 Participants	1 Participants n=81 Participants	0 Participants n=200 Participants	1 Participants n=350 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=69 Participants	0 Participants n=81 Participants	1 Participants n=200 Participants	1 Participants n=350 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=69 Participants	0 Participants n=81 Participants	1 Participants n=200 Participants	1 Participants n=350 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	64 Participants n=69 Participants	76 Participants n=81 Participants	183 Participants n=200 Participants	323 Participants n=350 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	4 Participants n=69 Participants	5 Participants n=81 Participants	15 Participants n=200 Participants	24 Participants n=350 Participants
Race/Ethnicity, Customized Ethnicity · Missing	1 Participants n=69 Participants	0 Participants n=81 Participants	2 Participants n=200 Participants	3 Participants n=350 Participants
Estimated Glomerular Filtration Rate (eGFR) for randomization <45 mL/min per 1.73 m^2	3 Participants n=69 Participants • eGFR was meant to be collected for randomized participants (ASP1128 and Placebo) only.	9 Participants n=81 Participants • eGFR was meant to be collected for randomized participants (ASP1128 and Placebo) only.	—	12 Participants n=150 Participants • eGFR was meant to be collected for randomized participants (ASP1128 and Placebo) only.
Estimated Glomerular Filtration Rate (eGFR) for randomization >=45 mL/min per 1.73 m^2	66 Participants n=69 Participants • eGFR was meant to be collected for randomized participants (ASP1128 and Placebo) only.	72 Participants n=81 Participants • eGFR was meant to be collected for randomized participants (ASP1128 and Placebo) only.	—	138 Participants n=150 Participants • eGFR was meant to be collected for randomized participants (ASP1128 and Placebo) only.

PRIMARY outcome

Timeframe: From end of surgery up to 72 hrs

Population: FAS consisted of all randomized participants who received at least 1 dose of study treatment. The outcome measure was planned to be analyzed for ASP1128 and Placebo only.

Development of AKI was based on SCr criteria from the kidney disease improving global outcomes (KDIGO) guideline (i.e., increase in SCr ≥ 0.3 milligram per deciliter (mg/dL) [≥ 26.5 micromoles per liter {μmol/L}] within any 48 hours or increase in SCr to ≥ 1.5 times baseline within 72 hours after end of surgery [T0]). Percentage of participants who developed AKI-SCr72h were reported.

Outcome measures

Measure	ASP1128 n=69 Participants Participants received ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Placebo n=81 Participants Participants received placebo matched to ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.
Percentage of Participants Developing AKI Based on Serum Creatinine (SCr) Criteria Within 72 Hrs From End of Surgery (AKI-SCr72h)	24.6 percentage of participants	21.0 percentage of participants

SECONDARY outcome

Timeframe: From end of surgery up to 7 days

Population: FAS Population. The outcome measure was planned to be analyzed for ASP1128 and Placebo only.

Development of AKI was based on SCr criteria from the KDIGO guideline (i.e., increase in SCr ≥ 0.3 mg/dL [≥ 26.5 μmol/L] within any 48 hours or increase in SCr to ≥ 1.5 times baseline within 7 days after T0). Percentage of participants who developed AKI-SCr7d were reported.

Outcome measures

Measure	ASP1128 n=69 Participants Participants received ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Placebo n=81 Participants Participants received placebo matched to ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.
Percentage of Participants Developing AKI Based on Serum Creatinine (SCr) Criteria Within 7 Days From End of Surgery (AKI-SCr7d)	30.4 percentage of participants	23.5 percentage of participants

SECONDARY outcome

Timeframe: From end of surgery up to 72 hrs

Population: FAS Population. The outcome measure was planned to be analyzed for ASP1128 and Placebo only.

Development of AKI was based on all captured criteria from KDIGO guideline (i.e., AKI-SCr stage 1 to 3: increase in SCr ≥ 0.3 mg/dL [≥ 26.5 μmol/L] within any 48 hours, increase in SCr to ≥ 1.5 times baseline, and/or AKI-urinary output (UO) stage 2 and 3: urine volume < 0.5 mL/kg per hour for 12 consecutive hours) within 72 hours after T0. Percentage of participants who developed AKI-KDIGO72h were reported.

Outcome measures

Measure	ASP1128 n=69 Participants Participants received ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Placebo n=81 Participants Participants received placebo matched to ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.
Percentage of Participants Developing AKI Based on All Captured Criteria Within 72 Hrs From End of Surgery (AKI-KDIGO72h)	79.7 percentage of participants	77.8 percentage of participants

SECONDARY outcome

Timeframe: From end of surgery up to 7 days

Population: FAS Population. The outcome measure was planned to be analyzed for ASP1128 and Placebo only.

Development of AKI was based on all captured criteria from KDIGO guideline (i.e., AKI-SCr stage 1 to 3: increase in SCr ≥ 0.3 mg/dL [≥ 26.5 μmol/L] within any 48 hours, increase in SCr to ≥ 1.5 times baseline, and/or AKI-urinary output (UO) stage 2 and 3: urine volume < 0.5 milliliter per kilogram (mL/kg) per hour for 12 consecutive hours) within 7 days after T0. Percentage of participants who developed AKI-KDIGO7d were reported.

Outcome measures

Measure	ASP1128 n=69 Participants Participants received ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Placebo n=81 Participants Participants received placebo matched to ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.
Percentage of Participants Developing AKI Based on All Captured Criteria Within 7 Days From End of Surgery (AKI-KDIGO7d)	88.4 percentage of participants	85.2 percentage of participants

SECONDARY outcome

Timeframe: From day of surgery up to 30 days

Population: FAS Population. The outcome measure was planned to be analyzed for ASP1128 and Placebo only.

MAKE30 was defined as all-cause mortality, renal replacement therapy (RRT) and/or ≥ 25% sustained reduction in estimated glomerular filtration rate (eGFR) based on SCr within 30 days after day of surgery. Percentage of participants with MAKE30 were reported.

Outcome measures

Measure	ASP1128 n=69 Participants Participants received ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Placebo n=81 Participants Participants received placebo matched to ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.
Percentage of Participants With Major Adverse Kidney Events (MAKE) Within 30 Days After Day of Surgery (MAKE30)	13.0 percentage of participants	11.1 percentage of participants

SECONDARY outcome

Timeframe: From day of surgery up to 90 days

Population: FAS Population. The outcome measure was planned to be analyzed for ASP1128 and Placebo only.

MAKE90 was defined as all-cause mortality, renal replacement therapy (RRT) and/or ≥ 25% sustained reduction in estimated glomerular filtration rate (eGFR) based on SCr within 90 days after day of surgery. Percentage of participants with MAKE90 were reported.

Outcome measures

Measure	ASP1128 n=69 Participants Participants received ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Placebo n=81 Participants Participants received placebo matched to ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.
Percentage of Participants With MAKE Within 90 Days After Day of Surgery (MAKE90)	15.9 percentage of participants	9.9 percentage of participants

Adverse Events

ASP1128

Serious events: 36 serious events

Other events: 29 other events

Deaths: 3 deaths

Placebo

Serious events: 45 serious events

Other events: 29 other events

Deaths: 2 deaths

Observational Cohort

Serious events: 34 serious events

Other events: 73 other events

Deaths: 6 deaths

Serious adverse events

Measure	ASP1128 n=69 participants at risk Participants received ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Placebo n=81 participants at risk Participants received placebo matched to ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Observational Cohort n=200 participants at risk Participant with postoperative negative NephroCheck® (NC) (AKIRisk score was ≤ 0.3 ng/mL\^2/1000 at all assessments between 2 to 22 hours after time point 0 (T0) were followed up for 90 days in observational cohort. Participants did not receive any intervention.
Blood and lymphatic system disorders Thrombocytopenia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Acute left ventricular failure	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Acute myocardial infarction	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Arrhythmia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Atrial fibrillation	11.6% 8/69 • Number of events 10 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	29.6% 24/81 • Number of events 26 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Atrial flutter	2.9% 2/69 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Atrioventricular block complete	2.9% 2/69 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	2.5% 2/81 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Cardiac arrest	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Cardiac failure	2.9% 2/69 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Cardiac failure acute	2.9% 2/69 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Cardiac failure congestive	4.3% 3/69 • Number of events 4 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Cardiac tamponade	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Cardiogenic shock	2.9% 2/69 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Nodal arrhythmia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Pericardial effusion	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Sinus node dysfunction	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Tachycardia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Ventricular tachycardia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Gastrointestinal disorders Dyspepsia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Gastrointestinal disorders Impaired gastric emptying	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Gastrointestinal disorders Intestinal ischaemia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Gastrointestinal disorders Megacolon	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
General disorders Multiple organ dysfunction syndrome	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Hepatobiliary disorders Hepatic failure	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Hepatobiliary disorders Hyperbilirubinaemia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Infections and infestations Abdominal abscess	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Infections and infestations Escherichia urinary tract infection	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	2.5% 2/81 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Infections and infestations Pneumonia	4.3% 3/69 • Number of events 4 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	2.5% 2/81 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Infections and infestations Sepsis	2.9% 2/69 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Infections and infestations Wound infection	2.9% 2/69 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Anaemia postoperative	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Brachial plexus injury	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Postoperative delirium	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Postoperative respiratory failure	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Postoperative thoracic procedure complication	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Procedural pneumothorax	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Investigations Aspartate aminotransferase increased	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Metabolism and nutrition disorders Dehydration	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Metabolism and nutrition disorders Fluid overload	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Metabolism and nutrition disorders Hypokalaemia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Metabolism and nutrition disorders Malnutrition	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Nervous system disorders Cerebrovascular accident	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Nervous system disorders Embolic stroke	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Nervous system disorders Encephalopathy	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Nervous system disorders Presyncope	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Nervous system disorders Seizure	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Nervous system disorders Unresponsive to stimuli	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Product Issues Lead dislodgement	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Psychiatric disorders Delirium	2.9% 2/69 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	2.5% 2/81 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Renal and urinary disorders Acute kidney injury	21.7% 15/69 • Number of events 15 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	13.6% 11/81 • Number of events 13 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	9.0% 18/200 • Number of events 21 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Renal and urinary disorders Chronic kidney disease	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Renal and urinary disorders Renal failure	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Reproductive system and breast disorders Prostatitis	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	10.1% 7/69 • Number of events 7 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	8.6% 7/81 • Number of events 8 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.5% 3/200 • Number of events 3 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Haemothorax	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	2.5% 2/81 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.5% 3/200 • Number of events 4 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.3% 3/69 • Number of events 3 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Surgical and medical procedures Wound drainage	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Vascular disorders Hypotension	2.9% 2/69 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Vascular disorders Hypovolaemic shock	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Vascular disorders Orthostatic hypotension	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Blood and lymphatic system disorders Anaemia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Blood and lymphatic system disorders Blood loss anaemia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Arteriospasm coronary	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Myocardial infarction	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Pulseless electrical activity	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Cardiac disorders Systolic anterior motion of mitral valve	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Gastrointestinal disorders Gastrointestinal ischaemia	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Gastrointestinal disorders Nausea	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Gastrointestinal disorders Vomiting	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
General disorders Death	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
General disorders Non-cardiac chest pain	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Infections and infestations Cellulitis	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Infections and infestations Wound abscess	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Agitation postoperative	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Cardiac valve replacement complication	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Investigations International normalised ratio increased	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Metabolism and nutrition disorders Lactic acidosis	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Nervous system disorders Cerebral ischaemia	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Nervous system disorders Hemiparesis	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.0% 2/200 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Nervous system disorders Hydrocephalus	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Nervous system disorders Metabolic encephalopathy	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Nervous system disorders Somnolence	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Nervous system disorders Syncope	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Renal and urinary disorders Renal atrophy	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Mediastinal haemorrhage	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.0% 2/200 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.9% 2/69 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Productive cough	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.50% 1/200 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.

Other adverse events

Measure	ASP1128 n=69 participants at risk Participants received ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Placebo n=81 participants at risk Participants received placebo matched to ASP1128 solution administered by 15 minutes intravenous infusion within 24 hours after the end of surgery and thereafter once daily for 2 days.	Observational Cohort n=200 participants at risk Participant with postoperative negative NephroCheck® (NC) (AKIRisk score was ≤ 0.3 ng/mL\^2/1000 at all assessments between 2 to 22 hours after time point 0 (T0) were followed up for 90 days in observational cohort. Participants did not receive any intervention.
Blood and lymphatic system disorders Anaemia	4.3% 3/69 • Number of events 3 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	8.6% 7/81 • Number of events 7 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	2.5% 5/200 • Number of events 10 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Blood and lymphatic system disorders Blood loss anaemia	5.8% 4/69 • Number of events 4 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	3.7% 3/81 • Number of events 3 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	10.0% 20/200 • Number of events 20 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Blood and lymphatic system disorders Thrombocytopenia	8.7% 6/69 • Number of events 6 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	2.5% 2/81 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	9.5% 19/200 • Number of events 19 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Gastrointestinal disorders Constipation	18.8% 13/69 • Number of events 13 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	16.0% 13/81 • Number of events 13 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	5.5% 11/200 • Number of events 11 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Gastrointestinal disorders Nausea	7.2% 5/69 • Number of events 5 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	9.9% 8/81 • Number of events 8 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	10.0% 20/200 • Number of events 20 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Metabolism and nutrition disorders Decreased appetite	5.8% 4/69 • Number of events 4 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Metabolism and nutrition disorders Hypocalcaemia	7.2% 5/69 • Number of events 5 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	2.5% 2/81 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	5.0% 10/200 • Number of events 10 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Metabolism and nutrition disorders Hypokalaemia	5.8% 4/69 • Number of events 4 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	3.7% 3/81 • Number of events 3 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.5% 3/200 • Number of events 3 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Psychiatric disorders Insomnia	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	6.2% 5/81 • Number of events 5 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/200 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	13.0% 9/69 • Number of events 9 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	2.5% 2/81 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.5% 3/200 • Number of events 3 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Vascular disorders Hypotension	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	6.2% 5/81 • Number of events 5 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	17.0% 34/200 • Number of events 34 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Blood and lymphatic system disorders Leukocytosis	2.9% 2/69 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	2.5% 2/81 • Number of events 2 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	5.5% 11/200 • Number of events 11 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Incision site pain	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	6.5% 13/200 • Number of events 13 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Injury, poisoning and procedural complications Procedural pain	4.3% 3/69 • Number of events 3 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	3.7% 3/81 • Number of events 3 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	23.0% 46/200 • Number of events 46 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	5.5% 11/200 • Number of events 11 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	0.00% 0/81 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	6.5% 13/200 • Number of events 13 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Metabolism and nutrition disorders Hyperglycaemia	4.3% 3/69 • Number of events 3 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	5.0% 10/200 • Number of events 10 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/69 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	4.9% 4/81 • Number of events 4 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	6.5% 13/200 • Number of events 13 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.
Vascular disorders Hypertension	1.4% 1/69 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	1.2% 1/81 • Number of events 1 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.	6.5% 13/200 • Number of events 13 • Randomization Cohort (ASP1128/Placebo): From first dosing up to end of study visit (up to 90 days) Observational Cohort: From enrollment up to end of study visit (up to 90 days) ASP1128/Placebo: Safety Analysis Set. Observational Cohort (OC): Participants in OC. For randomization cohort, AEs were collected until visit 9 (Day 30). For participants discontinued from study prior to visit 9, AEs were collected until Day 90. After visit 9 until visit 10(Day 90), only serious AEs were collected. For OC, AEs were collected until 24 hours after T0, however, AEs related to MAKE were collected until Day 90. All-cause mortality: All reported deaths after first dosing/enrollment.

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