Trial Outcomes & Findings for A Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of TIN816 in Patients at Risk for Acute Kidney Injury Following Cardiac Surgery. (NCT NCT05524051)

Last Updated: 2026-04-02

Results Overview

The log-transformed ratio of the highest serum creatinine value up to and including Study Day 6 vs baseline was analysed by a linear model. The estimated mean and 90% confidence interval of the difference in log-transformed ratios vs baseline between each TIN816 treatment group and placebo were then back-transformed to obtain the geometric mean ratio. The geometric mean ratio (GMR) represents the ratio between TIN816 and placebo geometric mean estimates for the serum creatinine Day 6 to baseline geometric mean estimates.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

102 participants

Primary outcome timeframe

Baseline, Day 1 - Day 6

Results posted on

2026-04-02

Participant Flow

Participants were enrolled at 36 investigative sites in 15 countries. Participants were originally randomized in a ratio of 1:1 (TIN816 2 mg/kg:placebo). After a protocol amendment participants were randomized in a ratio of 3:1 (TIN816 4 mg/kg:placebo).

The study consisted of a pre-operative period (screening visit).

Participant milestones

Participant milestones
Measure	TIN816 2 mg/kg TIN816 2 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 4 mg/kg TIN816 4 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	Placebo Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.
Overall Study STARTED	22	43	37
Overall Study COMPLETED	19	37	32
Overall Study NOT COMPLETED	3	6	5

Reasons for withdrawal

Reasons for withdrawal
Measure	TIN816 2 mg/kg TIN816 2 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 4 mg/kg TIN816 4 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	Placebo Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.
Overall Study Withdrawal by Subject	2	1	3
Overall Study Death	0	3	0
Overall Study Lost to Follow-up	0	0	1
Overall Study Randomized but not treated	1	2	1

Baseline Characteristics

A Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of TIN816 in Patients at Risk for Acute Kidney Injury Following Cardiac Surgery.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TIN816 2 mg/kg n=21 Participants TIN816 2 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 4 mg/kg n=41 Participants TIN816 4 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	Placebo n=36 Participants Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.	Total n=98 Participants Total of all reporting groups
Age, Continuous	70.7 years STANDARD_DEVIATION 7.99 • n=5 Participants	70.3 years STANDARD_DEVIATION 8.01 • n=5 Participants	71.9 years STANDARD_DEVIATION 6.85 • n=10 Participants	71.0 years STANDARD_DEVIATION 7.56 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	8 Participants n=5 Participants	9 Participants n=10 Participants	27 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	33 Participants n=5 Participants	27 Participants n=10 Participants	71 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	1 Participants n=5 Participants	1 Participants n=10 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	8 Participants n=5 Participants	5 Participants n=10 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized White	17 Participants n=5 Participants	21 Participants n=5 Participants	15 Participants n=10 Participants	53 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=5 Participants	0 Participants n=10 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	1 Participants n=5 Participants	10 Participants n=5 Participants	15 Participants n=10 Participants	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 1 - Day 6

Population: The pharmacodynamic (PD) analysis set included all participants with available PD data and without any protocol deviations with a relevant impact on PD data.

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 2 mg/kg n=21 Participants TIN816 2 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 4 mg/kg n=40 Participants TIN816 4 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.
Ratio of the Highest Serum Creatinine Value up to and Including Study Day 6 Versus Baseline	1.226 ratio Interval 1.08 to 1.39	1.215 ratio Interval 1.07 to 1.38	1.318 ratio Interval 1.18 to 1.48

SECONDARY outcome

Timeframe: Baseline, Day 8

Population: The safety analysis set included all participants who received any study treatment (TIN816 or Placebo).

AKI incidence over the first week after surgery (Day 1 to Day 8) was measured using the modified AKIN classification system, based on changes in serum creatinine compared to pre-operative value. Severity of AKI was assessed using three stages, with stage 1 being mild or least severe and stage 3 the most severe. Stage 1: Serum creatinine (SCr) ≥1.5 - \<2.0 x baseline within 7 days post-surgery Or ↑ SCr by ≥26.5 μmol/L (≥0.3 mg/dL) within 2 days post-surgery Stage 2: SCr ≥2.0 - \<3.0 x baseline within 7 days post-surgery Stage 3: SCr ≥3.0x baseline within 7 days post-surgery Or ↑ SCr to ≥353.6 μmol/L (4.0 mg/dL) AND by ≥44.2 μmol/L (0.5 mg/dL) within 7 days post-surgery Or Initiation of RRT within 7 days post-surgery

Outcome measures

Outcome measures
Measure	Placebo n=36 Participants Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 2 mg/kg n=21 Participants TIN816 2 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 4 mg/kg n=41 Participants TIN816 4 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.
Number of Participants With Maximum Acute Kidney Injury (AKI) Incidence Stages 1, 2 and 3 as Defined by Modified AKI Network Criteria No AKI	24 Participants	13 Participants	16 Participants
Number of Participants With Maximum Acute Kidney Injury (AKI) Incidence Stages 1, 2 and 3 as Defined by Modified AKI Network Criteria Stage 1	10 Participants	6 Participants	18 Participants
Number of Participants With Maximum Acute Kidney Injury (AKI) Incidence Stages 1, 2 and 3 as Defined by Modified AKI Network Criteria Stage 2	1 Participants	1 Participants	1 Participants
Number of Participants With Maximum Acute Kidney Injury (AKI) Incidence Stages 1, 2 and 3 as Defined by Modified AKI Network Criteria Stage 3	1 Participants	1 Participants	6 Participants

SECONDARY outcome

Timeframe: Day 1 pre-dose, Day 8, Day 30 and Day 90

Population: The immunogenicity (IG) analysis set included all participants with at least one available valid IG concentration measurement, who received any study drug and had no protocol deviations that impacted IG data.

Immunogenicity (IG) serum samples were collected to evaluate production of anti-TIN816 antibodies (anti-drug antibodies, ADAs).

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 2 mg/kg n=20 Participants TIN816 2 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 4 mg/kg n=40 Participants TIN816 4 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.
Number of Participants With Anti-TIN816 Antibodies Day 30 - positive	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-TIN816 Antibodies Day 1 pre-dose - positive	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-TIN816 Antibodies Day 8 - positive	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-TIN816 Antibodies Day 90 - positive	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Day 30

Population: The safety analysis set included all participants who received any study treatment (TIN816 or Placebo).

The number of participants having major adverse kidney event at Day 30 (MAKE30) was assessed using the following components: 1. death through day 30, 2. initiation of renal replacement therapy (RRT) through day 30, and 3. ≥25% reduction in eGFR from baseline to 30 days after surgery.

Outcome measures

Outcome measures
Measure	Placebo n=36 Participants Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 2 mg/kg n=21 Participants TIN816 2 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 4 mg/kg n=41 Participants TIN816 4 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.
Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 30 (MAKE30) Death through day 30	0 Participants	0 Participants	3 Participants
Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 30 (MAKE30) Participants with any MAKE30	6 Participants	4 Participants	11 Participants
Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 30 (MAKE30) Initiation of renal replacement therapy to day 30	1 Participants	0 Participants	3 Participants
Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 30 (MAKE30) ≥25% eGFR reduction from baseline to day 30	5 Participants	4 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline, Day 90

Population: The safety analysis set included all participants who received any study treatment (TIN816 or Placebo).

The number of participants having major adverse kidney event at Day 90 (MAKE90) was assessed using the following components: 1. death through day 90, 2. initiation of renal replacement therapy (RRT) through day 90, and 3. ≥25% reduction in eGFR from baseline to 90 days after surgery.

Outcome measures

Outcome measures
Measure	Placebo n=36 Participants Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 2 mg/kg n=21 Participants TIN816 2 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 4 mg/kg n=41 Participants TIN816 4 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.
Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 90 (MAKE90) Participants with any MAKE90	2 Participants	2 Participants	10 Participants
Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 90 (MAKE90) Death through day 90	0 Participants	0 Participants	3 Participants
Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 90 (MAKE90) Initiation of renal replacement therapy to day 90	1 Participants	0 Participants	3 Participants
Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 90 (MAKE90) ≥25% eGFR reduction from baseline to day 90	1 Participants	2 Participants	5 Participants

Adverse Events

TIN816 2 mg/kg

Serious events: 6 serious events

Other events: 17 other events

Deaths: 0 deaths

TIN816 4 mg/kg

Serious events: 16 serious events

Other events: 30 other events

Deaths: 3 deaths

Placebo

Serious events: 9 serious events

Other events: 26 other events

Deaths: 0 deaths

Total

Serious events: 31 serious events

Other events: 73 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	TIN816 2 mg/kg n=21 participants at risk TIN816 2 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	TIN816 4 mg/kg n=41 participants at risk TIN816 4 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	Placebo n=36 participants at risk Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.	Total n=98 participants at risk Total
Cardiac disorders Bradycardia	4.8% 1/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	7.3% 3/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	6.1% 6/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Cardiac disorders Cardiogenic shock	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.0% 2/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Cardiac disorders Sinus tachycardia	9.5% 2/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.4% 1/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.8% 1/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.1% 4/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Gastrointestinal disorders Constipation	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	7.3% 3/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	11.1% 4/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	7.1% 7/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Gastrointestinal disorders Diarrhoea	9.5% 2/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.4% 1/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.8% 1/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.1% 4/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Gastrointestinal disorders Functional gastrointestinal disorder	9.5% 2/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.0% 2/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Gastrointestinal disorders Nausea	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	7.3% 3/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	8.3% 3/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	6.1% 6/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Gastrointestinal disorders Vomiting	9.5% 2/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.9% 2/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.8% 1/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.1% 5/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Cardiac disorders Atrioventricular block complete	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.4% 1/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	3.1% 3/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Blood and lymphatic system disorders Anaemia	23.8% 5/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	26.8% 11/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	22.2% 8/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	24.5% 24/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Blood and lymphatic system disorders Leukocytosis	4.8% 1/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	12.2% 5/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.8% 1/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	7.1% 7/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Blood and lymphatic system disorders Thrombocytopenia	9.5% 2/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	9.8% 4/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	8.3% 3/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	9.2% 9/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Cardiac disorders Atrial fibrillation	28.6% 6/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	34.1% 14/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	13.9% 5/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	25.5% 25/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
General disorders Oedema peripheral	4.8% 1/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	8.3% 3/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.1% 4/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
General disorders Systemic inflammatory response syndrome	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.0% 2/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Hepatobiliary disorders Liver injury	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	7.3% 3/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	3.1% 3/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Infections and infestations Pneumonia	4.8% 1/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	9.8% 4/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.1% 5/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Infections and infestations Urinary tract infection	14.3% 3/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.9% 2/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.1% 5/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Injury, poisoning and procedural complications Anaemia postoperative	4.8% 1/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	7.3% 3/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.1% 4/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Injury, poisoning and procedural complications Procedural nausea	4.8% 1/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.4% 1/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.1% 4/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	9.8% 4/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.1% 4/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Injury, poisoning and procedural complications Vasoplegia syndrome	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.0% 2/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Investigations Blood bilirubin increased	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.0% 2/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Investigations Haemoglobin decreased	4.8% 1/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	3.1% 3/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Investigations Platelet count decreased	9.5% 2/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.9% 2/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	6.1% 6/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	7.3% 3/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.1% 5/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Metabolism and nutrition disorders Hypervolaemia	4.8% 1/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	9.8% 4/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	11.1% 4/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	9.2% 9/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Metabolism and nutrition disorders Hypokalaemia	9.5% 2/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.4% 1/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.8% 1/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.1% 4/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Psychiatric disorders Delirium	14.3% 3/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.9% 2/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	8.3% 3/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	8.2% 8/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Psychiatric disorders Insomnia	4.8% 1/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.9% 2/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.1% 5/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Renal and urinary disorders Acute kidney injury	14.3% 3/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	39.0% 16/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	25.0% 9/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	28.6% 28/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Renal and urinary disorders Proteinuria	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	7.3% 3/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	0.00% 0/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	3.1% 3/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.8% 1/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	9.8% 4/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	7.1% 7/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Respiratory, thoracic and mediastinal disorders Pneumothorax	4.8% 1/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.4% 1/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.1% 4/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.9% 2/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	5.6% 2/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.1% 4/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	9.5% 2/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.4% 1/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.8% 1/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.1% 4/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Vascular disorders Hypertension	0.00% 0/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	2.4% 1/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	8.3% 3/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	4.1% 4/98 • Adverse events were reported up to approximately 90 days after administration of study drug.
Vascular disorders Hypotension	9.5% 2/21 • Adverse events were reported up to approximately 90 days after administration of study drug.	12.2% 5/41 • Adverse events were reported up to approximately 90 days after administration of study drug.	13.9% 5/36 • Adverse events were reported up to approximately 90 days after administration of study drug.	12.2% 12/98 • Adverse events were reported up to approximately 90 days after administration of study drug.