Trial Outcomes & Findings for Investigating FE 202158 as Potential Primary Treatment in Patients With Early Septic Shock (NCT NCT01612676)

Last Updated: 2017-03-23

Results Overview

Mean arterial pressure (MAP) was measured intra-arterially on a continuous basis. Success percentage of patients maintaining target/adequate MAP (\>60 mmHg) without norepinephrine is presented.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points.

Results posted on

2017-03-23

Participant Flow

The patients were recruited at the respective intensive care units at four centers (3 in Belgium and 1 in Denmark) between 05 Jul 2012 to 15 Nov 2013.

Of the 159 patients screened, 31 patients were randomised and 30 patients were dosed. One patient in the 3.75 ng/kg/min dose group did not receive any study treatment due to an adverse event (elevation of troponin) recorded prior to infusion.

Participant milestones

Participant milestones
Measure	Infusion Regimen 1: 3.75 ng/kg/Min FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Overall Study STARTED	6	7	5	13
Overall Study Dosed	5	7	5	13
Overall Study COMPLETED	4	3	4	10
Overall Study NOT COMPLETED	2	4	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Infusion Regimen 1: 3.75 ng/kg/Min FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Overall Study Adverse Event	2	3	1	3
Overall Study Protocol Violation	0	1	0	0

Baseline Characteristics

Investigating FE 202158 as Potential Primary Treatment in Patients With Early Septic Shock

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Infusion Regimen 1 n=5 Participants FE 202158 0.1 mg/ml (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2 n=7 Participants FE 202158 0.1 mg/ml (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3 n=5 Participants FE 202158 0.1 mg/ml (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4 n=13 Participants FE 202158 0.1 mg/ml (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Total n=30 Participants Total of all reporting groups
Age, Continuous	69.0 years STANDARD_DEVIATION 12.7 • n=5 Participants	67.9 years STANDARD_DEVIATION 13.7 • n=7 Participants	64.8 years STANDARD_DEVIATION 10.1 • n=5 Participants	67.6 years STANDARD_DEVIATION 13.2 • n=4 Participants	67.4 years STANDARD_DEVIATION 12.2 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	10 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants	20 Participants n=21 Participants
Weight	66.6 kg STANDARD_DEVIATION 13.5 • n=5 Participants	74.7 kg STANDARD_DEVIATION 17.7 • n=7 Participants	81.3 kg STANDARD_DEVIATION 8.0 • n=5 Participants	78.9 kg STANDARD_DEVIATION 15.3 • n=4 Participants	76.3 kg STANDARD_DEVIATION 14.8 • n=21 Participants
Total Sequential Organ Failure Assessment Score	11 Score on scale STANDARD_DEVIATION 3.32 • n=5 Participants	10 Score on scale STANDARD_DEVIATION 2.31 • n=7 Participants	8.8 Score on scale STANDARD_DEVIATION 3.19 • n=5 Participants	9.31 Score on scale STANDARD_DEVIATION 3.01 • n=4 Participants	9.67 Score on scale STANDARD_DEVIATION 2.88 • n=21 Participants
Septic shock characteristic: Primary infection type Bacterial	4 patients n=5 Participants	6 patients n=7 Participants	3 patients n=5 Participants	12 patients n=4 Participants	25 patients n=21 Participants
Septic shock characteristic: Primary infection type Unknown	0 patients n=5 Participants	1 patients n=7 Participants	1 patients n=5 Participants	1 patients n=4 Participants	3 patients n=21 Participants
Septic shock characteristic: Primary infection type Other	1 patients n=5 Participants	0 patients n=7 Participants	1 patients n=5 Participants	0 patients n=4 Participants	2 patients n=21 Participants
Septic shock characteristic: Primary infection location Abdominal cavity	1 patients n=5 Participants	5 patients n=7 Participants	3 patients n=5 Participants	6 patients n=4 Participants	15 patients n=21 Participants
Septic shock characteristic: Primary infection location Lung	1 patients n=5 Participants	1 patients n=7 Participants	0 patients n=5 Participants	1 patients n=4 Participants	3 patients n=21 Participants
Septic shock characteristic: Primary infection location Urinary tract	0 patients n=5 Participants	1 patients n=7 Participants	1 patients n=5 Participants	4 patients n=4 Participants	6 patients n=21 Participants
Septic shock characteristic: Primary infection location Other	3 patients n=5 Participants	0 patients n=7 Participants	1 patients n=5 Participants	1 patients n=4 Participants	5 patients n=21 Participants
Septic shock characteristic: Primary infection location Unknown	0 patients n=5 Participants	0 patients n=7 Participants	0 patients n=5 Participants	1 patients n=4 Participants	1 patients n=21 Participants

PRIMARY outcome

Timeframe: Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points.

Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.

Mean arterial pressure (MAP) was measured intra-arterially on a continuous basis. Success percentage of patients maintaining target/adequate MAP (\>60 mmHg) without norepinephrine is presented.

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 1 (Post 1 h)	20.0 Percentage of patients Interval 4.4 to 49.0	42.9 Percentage of patients Interval 22.8 to 65.0	60.0 Percentage of patients Interval 32.7 to 83.1	7.7 Percentage of patients Interval 1.7 to 21.3
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 1 (Post 3 h)	20.0 Percentage of patients Interval 4.4 to 49.0	14.3 Percentage of patients Interval 3.1 to 37.1	60.0 Percentage of patients Interval 32.7 to 83.1	53.8 Percentage of patients Interval 38.7 to 68.4
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 1 (Post 6 h)	25.0 Percentage of patients Interval 5.4 to 58.2	14.3 Percentage of patients Interval 3.1 to 37.1	80.0 Percentage of patients Interval 51.0 to 95.6	76.9 Percentage of patients Interval 61.6 to 88.0
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 1 (Post 12 h)	60.0 Percentage of patients Interval 32.7 to 83.1	28.6 Percentage of patients Interval 12.0 to 51.7	80.0 Percentage of patients Interval 51.0 to 95.6	53.8 Percentage of patients Interval 38.7 to 68.4
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 1 (Post 18 h)	60.0 Percentage of patients Interval 32.7 to 83.1	42.9 Percentage of patients Interval 22.8 to 65.0	80.0 Percentage of patients Interval 51.0 to 95.6	66.7 Percentage of patients Interval 50.3 to 80.2
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 1 (Post 24 h)	80.0 Percentage of patients Interval 51.0 to 95.6	42.9 Percentage of patients Interval 22.8 to 65.0	80.0 Percentage of patients Interval 51.0 to 95.6	61.5 Percentage of patients Interval 46.1 to 75.2
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 2 (Post 36 h)	80.0 Percentage of patients Interval 51.0 to 95.6	66.7 Percentage of patients Interval 41.5 to 86.0	80.0 Percentage of patients Interval 51.0 to 95.6	61.5 Percentage of patients Interval 46.1 to 75.2
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 2 (Post 48 h)	80.0 Percentage of patients Interval 51.0 to 95.6	50.0 Percentage of patients Interval 26.9 to 73.1	80.0 Percentage of patients Interval 51.0 to 95.6	76.9 Percentage of patients Interval 61.6 to 88.0
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 3 (Post 72 h)	80.0 Percentage of patients Interval 51.0 to 95.6	66.7 Percentage of patients Interval 41.5 to 86.0	80.0 Percentage of patients Interval 51.0 to 95.6	69.2 Percentage of patients Interval 53.7 to 81.8
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 4 (Post 96 h)	80.0 Percentage of patients Interval 51.0 to 95.6	80.0 Percentage of patients Interval 51.0 to 95.6	80.0 Percentage of patients Interval 51.0 to 95.6	76.9 Percentage of patients Interval 61.6 to 88.0
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 5 (Post 120 h)	80.0 Percentage of patients Interval 51.0 to 95.6	80.0 Percentage of patients Interval 51.0 to 95.6	80.0 Percentage of patients Interval 51.0 to 95.6	84.6 Percentage of patients Interval 69.9 to 93.6
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 6 (Post 144 h)	80.0 Percentage of patients Interval 51.0 to 95.6	80.0 Percentage of patients Interval 51.0 to 95.6	80.0 Percentage of patients Interval 51.0 to 95.6	84.6 Percentage of patients Interval 69.9 to 93.6
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine Day 7 (Post 168 h)	80.0 Percentage of patients Interval 51.0 to 95.6	80.0 Percentage of patients Interval 51.0 to 95.6	80.0 Percentage of patients Interval 51.0 to 95.6	76.9 Percentage of patients Interval 61.6 to 88.0

PRIMARY outcome

Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.

Cumulative dose of FE 202158 was calculated from Day 1 up to Day 7.

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Cumulative Dose of FE 202158 Day 5 (Post 120 h)	4523.9 ng/kg Interval 3900.8 to 5146.9	12865.3 ng/kg Interval 9561.7 to 16168.9	7999.8 ng/kg Interval 4765.3 to 11234.3	6621.8 ng/kg Interval 5033.5 to 8210.1
Cumulative Dose of FE 202158 Day 6 (Post 144 h)	4523.9 ng/kg Interval 3900.8 to 5146.9	13543.7 ng/kg Interval 9724.0 to 17363.3	7999.8 ng/kg Interval 4765.3 to 11234.3	6696.5 ng/kg Interval 5052.9 to 8340.1
Cumulative Dose of FE 202158 Day 1 (Post 12 h)	2451 ng/kg Interval 2226.3 to 2675.8	3276.3 ng/kg Interval 2941.3 to 3611.3	2946 ng/kg Interval 2426.2 to 3465.8	2377 ng/kg Interval 2220.2 to 2533.7
Cumulative Dose of FE 202158 Day 1 (Post 24 h)	4217.4 ng/kg Interval 3736.5 to 4698.3	5502.2 ng/kg Interval 4698.7 to 6305.7	4927.3 ng/kg Interval 4064.8 to 5789.8	3818.8 ng/kg Interval 3429.6 to 4208.0
Cumulative Dose of FE 202158 Day 2 (Post 36 h)	4463.9 ng/kg Interval 3877.0 to 5050.7	7535.9 ng/kg Interval 6206.2 to 8865.7	5842 ng/kg Interval 4554.6 to 7129.4	4619.2 ng/kg Interval 4005.0 to 5233.4
Cumulative Dose of FE 202158 Day 2 (Post 48 h)	4523.9 ng/kg Interval 3900.8 to 5146.9	9185 ng/kg Interval 7405.2 to 10963.9	6716 ng/kg Interval 4674.3 to 8757.6	5225 ng/kg Interval 4401.7 to 6048.3
Cumulative Dose of FE 202158 Day 3 (Post 72 h)	4523.9 ng/kg Interval 3900.8 to 5146.9	11511.4 ng/kg Interval 9096.1 to 13926.7	7902 ng/kg Interval 4758.8 to 11045.1	5860.1 ng/kg Interval 4763.9 to 6956.4
Cumulative Dose of FE 202158 Day 4 (Post 96 h)	4523.9 ng/kg Interval 3900.8 to 5146.9	12204.6 ng/kg Interval 9365.7 to 15043.4	7999.8 ng/kg Interval 4765.3 to 11234.3	6298.6 ng/kg Interval 4939.5 to 7657.7
Cumulative Dose of FE 202158 Day 7 (Post 168 h)	4523.9 ng/kg Interval 3900.8 to 5146.9	13543.7 ng/kg Interval 9724.0 to 17363.3	7999.8 ng/kg Interval 4765.3 to 11234.3	7003.7 ng/kg Interval 5126.0 to 8881.5

PRIMARY outcome

Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.

Infusion rate of FE 202158 was presented from Day 1 up to Day 7.

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Infusion Rate of FE 202158 Day 1 (Post 12 h)	3.25 ng/kg/min Standard Deviation 1.29	4.13 ng/kg/min Standard Deviation 2.09	3.08 ng/kg/min Standard Deviation 2.56	2.43 ng/kg/min Standard Deviation 1.41
Infusion Rate of FE 202158 Day 1 (Post 24 h)	0.94 ng/kg/min Standard Deviation 1.88	3.39 ng/kg/min Standard Deviation 2.37	1.59 ng/kg/min Standard Deviation 2.19	1.39 ng/kg/min Standard Deviation 1.65
Infusion Rate of FE 202158 Day 2 (Post 36 h)	0.23 ng/kg/min Standard Deviation 0.47	2.66 ng/kg/min Standard Deviation 2.27	2.08 ng/kg/min Standard Deviation 2.77	1.25 ng/kg/min Standard Deviation 1.76
Infusion Rate of FE 202158 Day 2 (Post 48 h)	0.00 ng/kg/min Standard Deviation 0.00	2.51 ng/kg/min Standard Deviation 2.29	1.79 ng/kg/min Standard Deviation 3.57	0.69 ng/kg/min Standard Deviation 1.28
Infusion Rate of FE 202158 Day 3 (Post 72 h)	0.00 ng/kg/min Standard Deviation 0.00	0.82 ng/kg/min Standard Deviation 2.02	0.61 ng/kg/min Standard Deviation 1.22	0.39 ng/kg/min Standard Deviation 1.08
Infusion Rate of FE 202158 Day 4 (Post 96 h)	0.00 ng/kg/min Standard Deviation 0.00	0.00 ng/kg/min Standard Deviation 0.00	0.00 ng/kg/min Standard Deviation 0.00	0.33 ng/kg/min Standard Deviation 1.08
Infusion Rate of FE 202158 Day 5 (Post 120 h)	0.00 ng/kg/min Standard Deviation 0.00	0.99 ng/kg/min Standard Deviation 2.21	0.00 ng/kg/min Standard Deviation 0.00	0.00 ng/kg/min Standard Deviation 0.00
Infusion Rate of FE 202158 Day 6 (Post 144 h)	0.00 ng/kg/min Standard Deviation 0.00	0.00 ng/kg/min Standard Deviation 0.00	0.00 ng/kg/min Standard Deviation 0.00	0.00 ng/kg/min Standard Deviation 0.00
Infusion Rate of FE 202158 Day 7 (Post 168 h)	0.00 ng/kg/min Standard Deviation 0.00	0.00 ng/kg/min Standard Deviation 0.00	0.00 ng/kg/min Standard Deviation 0.00	0.33 ng/kg/min Standard Deviation 1.08

PRIMARY outcome

Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed. One patient in the 7.5 ng/kg/min group started the vasopressor support without prior administration of norepinephrine, and MAP was adequately controlled as needed.

Norepinephrine was infused as required to maintain the target mean arterial pressure, if the highest infusion rate allowed of experimental drug FE 202158 did not provide adequate vasopressor support. Cumulative dose of norepinephrine was calculated from Day 1 up to Day 7.

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=4 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Cumulative Dose of Norepinephrine Day 1 (Post 12 h)	358.1 µg/kg Interval 91.8 to 624.3	172.1 µg/kg Interval 96.5 to 247.8	118.0 µg/kg Interval 12.7 to 223.3	73.1 µg/kg Interval 47.2 to 99.0
Cumulative Dose of Norepinephrine Day 1 (Post 24 h)	720.8 µg/kg Interval 131.8 to 1309.7	338.0 µg/kg Interval 171.5 to 504.6	357.5 µg/kg Interval 17.8 to 697.2	149.5 µg/kg Interval 90.4 to 208.6
Cumulative Dose of Norepinephrine Day 2 (Post 36 h)	720.8 µg/kg Interval 131.8 to 1309.7	406.2 µg/kg Interval 214.7 to 597.6	778.2 µg/kg Interval 26.9 to 1529.5	197.8 µg/kg Interval 111.4 to 284.2
Cumulative Dose of Norepinephrine Day 2 (Post 48 h)	720.8 µg/kg Interval 131.8 to 1309.7	495.5 µg/kg Interval 296.4 to 694.5	778.4 µg/kg Interval 27.2 to 1529.7	232.8 µg/kg Interval 120.6 to 345.1
Cumulative Dose of Norepinephrine Day 3 (Post 72 h)	720.8 µg/kg Interval 131.8 to 1309.7	669.0 µg/kg Interval 390.8 to 947.2	778.4 µg/kg Interval 27.2 to 1529.7	279.1 µg/kg Interval 129.5 to 428.7
Cumulative Dose of Norepinephrine Day 4 (Post 96 h)	720.8 µg/kg Interval 131.8 to 1309.7	829.6 µg/kg Interval 438.1 to 1221.1	778.4 µg/kg Interval 27.2 to 1529.7	303.1 µg/kg Interval 133.6 to 472.6
Cumulative Dose of Norepinephrine Day 5 (Post 120 h)	720.8 µg/kg Interval 131.8 to 1309.7	1039.5 µg/kg Interval 473.7 to 1605.2	778.4 µg/kg Interval 27.2 to 1529.7	307.8 µg/kg Interval 134.4 to 481.2
Cumulative Dose of Norepinephrine Day 6 (Post 144 h)	720.8 µg/kg Interval 131.8 to 1309.7	1152.0 µg/kg Interval 489.2 to 1814.7	778.4 µg/kg Interval 27.2 to 1529.7	307.8 µg/kg Interval 134.4 to 481.2
Cumulative Dose of Norepinephrine Day 7 (Post 168 h)	720.8 µg/kg Interval 131.8 to 1309.7	1152.0 µg/kg Interval 489.2 to 1814.7	778.4 µg/kg Interval 27.2 to 1529.7	311.1 µg/kg Interval 134.9 to 487.2

PRIMARY outcome

Norepinephrine was infused as required to maintain the target mean arterial pressure, if the highest infusion rate allowed of experimental drug FE 202158 did not provide adequate vasopressor support. Infusion rates and all changes in infusion rates of norepinephrine were recorded continuously during the 7 day maximum treatment period.

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=4 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Infusion Rate of Norepinephrine Day 4 (Post 96 h)	0.000 µg/kg/min Standard Deviation 0.000	0.184 µg/kg/min Standard Deviation 0.411	0.000 µg/kg/min Standard Deviation 0.000	0.005 µg/kg/min Standard Deviation 0.016
Infusion Rate of Norepinephrine Day 5 (Post 120 h)	0.000 µg/kg/min Standard Deviation 0.000	0.172 µg/kg/min Standard Deviation 0.385	0.000 µg/kg/min Standard Deviation 0.000	0.000 µg/kg/min Standard Deviation 0.000
Infusion Rate of Norepinephrine Day 6 (144 h)	0.000 µg/kg/min Standard Deviation 0.000	0.000 µg/kg/min Standard Deviation 0.000	0.000 µg/kg/min Standard Deviation 0.000	0.000 µg/kg/min Standard Deviation 0.000
Infusion Rate of Norepinephrine Day 2 (Post 36 h)	0.000 µg/kg/min Standard Deviation 0.000	0.049 µg/kg/min Standard Deviation 0.101	0.000 µg/kg/min Standard Deviation 0.000	0.061 µg/kg/min Standard Deviation 0.171
Infusion Rate of Norepinephrine Day 2 (Post 48 h)	0.000 µg/kg/min Standard Deviation 0.000	0.105 µg/kg/min Standard Deviation 0.215	0.004 µg/kg/min Standard Deviation 0.008	0.057 µg/kg/min Standard Deviation 0.188
Infusion Rate of Norepinephrine Day 3 (Post 72 h)	0.000 µg/kg/min Standard Deviation 0.000	0.120 µg/kg/min Standard Deviation 0.270	0.000 µg/kg/min Standard Deviation 0.000	0.024 µg/kg/min Standard Deviation 0.079
Infusion Rate of Norepinephrine Day 1 (Post 12 h)	0.341 µg/kg/min Standard Deviation 0.691	0.281 µg/kg/min Standard Deviation 0.444	0.215 µg/kg/min Standard Deviation 0.405	0.111 µg/kg/min Standard Deviation 0.197
Infusion Rate of Norepinephrine Day 1 (Post 24 h)	0.010 µg/kg/min Standard Deviation 0.020	0.222 µg/kg/min Standard Deviation 0.402	0.639 µg/kg/min Standard Deviation 1.280	0.089 µg/kg/min Standard Deviation 0.188
Infusion Rate of Norepinephrine Day 7 (Post 168 h)	0.000 µg/kg/min Standard Deviation 0.000	0.000 µg/kg/min Standard Deviation 0.000	0.000 µg/kg/min Standard Deviation 0.000	0.006 µg/kg/min Standard Deviation 0.021

PRIMARY outcome

Timeframe: Day 1 up to Day 28

Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.

The Kaplan-Meyer estimation of time to out of septic shock was estimated where time to (first) septic shock resolution was defined as time of end of infusion regimen. Intermittent off treatment periods were regarded as part of the shock duration. Time to all but one patient out of septic shock is presented.

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=30 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Time to Septic Shock Resolution 3.75 ng/kg/min (n=5)	23 Hours	—	—	—
Time to Septic Shock Resolution 5.0 ng/kg/min (n=7)	75 Hours	—	—	—
Time to Septic Shock Resolution 7.5 ng/kg/min (n=5)	37 Hours	—	—	—
Time to Septic Shock Resolution Modified 3.75 ng/kg/min (n=13)	89 Hours	—	—	—

SECONDARY outcome

Timeframe: Day 1 up to Day 7 post-infusion (Data collected on Day 1 at 24 h, Day 2 at 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points.

Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.

The urinary output was recorded every 24 hours up to Day 7, or as long as the patient was in intensive care unit.

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Urinary Output Day 1 (Post 24 h)	24.9 mL/kg Interval 16.0 to 33.8	21.8 mL/kg Interval 16.4 to 27.2	36.0 mL/kg Interval 27.0 to 45.1	24.1 mL/kg Interval 20.2 to 28.0
Urinary Output Day 2 (Post 48 h)	42.9 mL/kg Interval 26.7 to 59.1	31.0 mL/kg Interval 23.9 to 38.0	55.9 mL/kg Interval 41.8 to 69.9	48.1 mL/kg Interval 36.6 to 59.5
Urinary Output Day 3 (Post 72 h)	57.3 mL/kg Interval 32.3 to 82.3	43.2 mL/kg Interval 32.3 to 54.1	79.2 mL/kg Interval 58.0 to 100.4	72.3 mL/kg Interval 53.7 to 91.0
Urinary Output Day 4 (Post 96 h)	68.0 mL/kg Interval 37.6 to 98.4	58.8 mL/kg Interval 42.1 to 75.4	100.5 mL/kg Interval 74.4 to 126.7	94.0 mL/kg Interval 69.4 to 118.7
Urinary Output Day 5 (Post 120 h)	74.3 mL/kg Interval 42.3 to 106.3	73.3 mL/kg Interval 51.1 to 95.6	125.2 mL/kg Interval 94.3 to 156.1	106.2 mL/kg Interval 79.2 to 133.2
Urinary Output Day 6 (Post 144 h)	81.8 mL/kg Interval 46.6 to 116.9	85.9 mL/kg Interval 58.2 to 113.5	139.8 mL/kg Interval 104.7 to 175.0	111.9 mL/kg Interval 84.8 to 139.1
Urinary Output Day 7 (Post 168 h)	82.0 mL/kg Interval 46.8 to 117.2	96.1 mL/kg Interval 64.2 to 128.0	144.7 mL/kg Interval 108.2 to 181.2	115.1 mL/kg Interval 87.7 to 142.5

SECONDARY outcome

Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.

The fluid balance (accumulated input/output) was recorded in 24-hour collecting periods when the patient was in the intensive care unit and during the infusion of FE 202158.

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Fluid Balance Day 1 (Post 24 h)	50 mL/kg Interval 23.0 to 77.0	72 mL/kg Interval 60.0 to 85.0	62 mL/kg Interval 50.0 to 74.0	61 mL/kg Interval 52.0 to 69.0
Fluid Balance Day 2 (Post 48 h)	69 mL/kg Interval 34.0 to 103.0	128 mL/kg Interval 103.0 to 153.0	96 mL/kg Interval 78.0 to 113.0	75 mL/kg Interval 66.0 to 85.0
Fluid Balance Day 3 (Post 72 h)	75 mL/kg Interval 32.0 to 118.0	173 mL/kg Interval 141.0 to 206.0	115 mL/kg Interval 94.0 to 135.0	72 mL/kg Interval 61.0 to 83.0
Fluid Balance Day 4 (Post 96 h)	76 mL/kg Interval 30.0 to 122.0	189 mL/kg Interval 153.0 to 226.0	107 mL/kg Interval 90.0 to 124.0	68 mL/kg Interval 57.0 to 79.0
Fluid Balance Day 5 (Post 120 h)	80 mL/kg Interval 31.0 to 130.0	209 mL/kg Interval 172.0 to 247.0	90 mL/kg Interval 78.0 to 102.0	69 mL/kg Interval 57.0 to 81.0
Fluid Balance Day 6 (Post 144 h)	84 mL/kg Interval 31.0 to 138.0	209 mL/kg Interval 166.0 to 252.0	88 mL/kg Interval 75.0 to 100.0	76 mL/kg Interval 61.0 to 91.0
Fluid Balance Day 7 (Post 168 h)	90 mL/kg Interval 33.0 to 147.0	220 mL/kg Interval 174.0 to 267.0	98 mL/kg Interval 77.0 to 119.0	78 mL/kg Interval 62.0 to 95.0

SECONDARY outcome

Timeframe: Day 1 up to Day 2

Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.

Investigator reported outcome on FE 202158 performance. Answers were graded on a visual analogue scale (VAS) from 0 to 10, 0 being the worst and 10 being the best outcome.

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Summary of Investigator Reported Outcomes Onset of action adequate to reach target MAP	4.4 Score on scale Standard Deviation 3.78	3.57 Score on scale Standard Deviation 2.51	9.0 Score on scale Standard Deviation 1.22	7.85 Score on scale Standard Deviation 2.54
Summary of Investigator Reported Outcomes MAP maintained within desired boundaries (Day 1)	6.8 Score on scale Standard Deviation 2.77	3.86 Score on scale Standard Deviation 2.67	9 Score on scale Standard Deviation 1.22	7.69 Score on scale Standard Deviation 3.66
Summary of Investigator Reported Outcomes MAP maintained within desired boundaries (Day 2)	10 Score on scale Standard Deviation 0	4 Score on scale Standard Deviation 2.35	8.75 Score on scale Standard Deviation 1.26	6.71 Score on scale Standard Deviation 3.77
Summary of Investigator Reported Outcomes Confidence to use FE 202158 as primary treatment	6.5 Score on scale Standard Deviation 1.91	5.5 Score on scale Standard Deviation 2.43	9.5 Score on scale Standard Deviation 0.577	8.18 Score on scale Standard Deviation 2.44

SECONDARY outcome

Timeframe: Day 1 up to Day 28

Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.

Percentage of all the "Days alive and out/free of" intensive care unit, hospital, dialysis, or ventilation within Day 28 were summarized. Patients dying before or at Day 28 were counted as zero.

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Morbidity Assessment Days alive and out of intensive care unit	51.6 percentage of days within 28 days	31.4 percentage of days within 28 days	61.2 percentage of days within 28 days	58.8 percentage of days within 28 days
Morbidity Assessment Days alive and out of hospital	12.8 percentage of days within 28 days	3.6 percentage of days within 28 days	17.8 percentage of days within 28 days	26.2 percentage of days within 28 days
Morbidity Assessment Days alive and free of dialysis	60 percentage of days within 28 days	38.6 percentage of days within 28 days	80 percentage of days within 28 days	76.7 percentage of days within 28 days
Morbidity Assessment Days alive and free of ventilation	58.8 percentage of days within 28 days	39.6 percentage of days within 28 days	75.6 percentage of days within 28 days	73.9 percentage of days within 28 days

SECONDARY outcome

Timeframe: Day 1 up to Day 28

Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.

Collection of data on graded morbidity was performed on Day 28 in addition to the collection of data on time of stay in intensive care unit and hospital.

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Graded Morbidity Alive and out of hospital	2 patients	0 patients	2 patients	6 patients
Graded Morbidity In hospital (not intensive care unit)	1 patients	2 patients	2 patients	4 patients
Graded Morbidity In intensive care unit	1 patients	1 patients	0 patients	0 patients
Graded Morbidity Dead	1 patients	2 patients	1 patients	3 patients

SECONDARY outcome

Timeframe: Day 1 up to Day 28

Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.

Collection of data on mortality was performed on Day 28 in addition to the collection of data on time of stay in intensive care unit and hospital.

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Mortality Alive	4 patients	3 patients	4 patients	10 patients
Mortality Dead	1 patients	2 patients	1 patients	3 patients

SECONDARY outcome

Timeframe: Day 1 up to Day 7, and at follow-up assessments performed 24-72 hours after end of IMP infusion

Population: The safety analysis set comprised of all allocated and dosed patients and were analyzed according to the actual dosing regimen received.

Significant changes for vital signs (blood pressure, heart rate, mean arterial pressure), electrocardiogram (ECG), and laboratory parameters (clinical chemistry, haematology, haemostasis, and urinary parameters).

Outcome measures

Outcome measures
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=5 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 Participants FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.
Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram Patients with adverse effects on lab parameters	0 patients	0 patients	0 patients	0 patients
Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram Patients with adverse effects on vital signs	0 patients	0 patients	0 patients	0 patients
Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram Patients with adverse effects on electrocardiogram	0 patients	0 patients	0 patients	0 patients

Adverse Events

Infusion Regimen 1: 3.75 ng/kg/Min

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Infusion Regimen 2: 5.0 ng/kg/Min

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Infusion Regimen 3: 7.5 ng/kg/Min

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Infusion Regimen 4: Modified 3.75 ng/kg/Min

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

Total

Serious events: 10 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 participants at risk FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 participants at risk FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=5 participants at risk FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 participants at risk FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Total n=30 participants at risk Summation of adverse events in all treatment arms
Cardiac disorders Cardiac arrest	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Cardiac disorders Cardiac failure	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Cardiac disorders Cardiogenic shock	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Cardiac disorders Myocardial ischemia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Cardiac disorders Right ventricular failure	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	6.7% 2/30 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Intestinal ischemia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Hepatobiliary disorders Hepatic congestion	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Infections and infestations Endocarditis	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Infections and infestations Septic shock	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Nervous system disorders Cerebral haemorrhage	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Surgical and medical procedures Colostomy	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Vascular disorders Distributive shock	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Vascular disorders Peripheral ischemia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Vascular disorders Shock	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.

Other adverse events

Other adverse events
Measure	Infusion Regimen 1: 3.75 ng/kg/Min n=5 participants at risk FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 2: 5.0 ng/kg/Min n=7 participants at risk FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 3: 7.5 ng/kg/Min n=5 participants at risk FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Infusion Regimen 4: Modified 3.75 ng/kg/Min n=13 participants at risk FE 202158 0.1 mg/mL (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days.	Total n=30 participants at risk Summation of adverse events in all treatment arms
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Blood and lymphatic system disorders Anaemia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	6.7% 2/30 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	6.7% 2/30 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Cardiac disorders Atrial fibrillation	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	28.6% 2/7 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	10.0% 3/30 • Number of events 3 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Cardiac disorders Bradycardia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Cardiac disorders Cardiac failure	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Cardiac disorders Cyanosis	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Cardiac disorders Myocardial depression	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Cardiac disorders Palpitations	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Cardiac disorders Supraventricular tachycardia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	6.7% 2/30 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Nausea	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	15.4% 2/13 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	6.7% 2/30 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Abdominal compartment syndrome	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Abdominal pain	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Colitis	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Diarrhoea	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Gastritis	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Mouth haemorrhage	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Gastrointestinal disorders Oesophageal perforation	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
General disorders Hypothermia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
General disorders Medical device complication	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
General disorders Oedema peripheral	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Hepatobiliary disorders Cholelithiasis	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Hepatobiliary disorders Cytolytic hepatitis	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Hepatobiliary disorders Hepatic congestion	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Infections and infestations Pneumonia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Injury, poisoning and procedural complications Overdose	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Investigations Blood potassium decreased	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Investigations Troponin increased	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Metabolism and nutrition disorders Hypoglycaemia	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	28.6% 2/7 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	16.7% 5/30 • Number of events 5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	28.6% 2/7 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	6.7% 2/30 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Metabolism and nutrition disorders Fluid overload	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Metabolism and nutrition disorders Metabolic alkalosis	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Psychiatric disorders Anxiety	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	6.7% 2/30 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Psychiatric disorders Confusional state	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Renal and urinary disorders Renal failure acute	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	6.7% 2/30 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Respiratory, thoracic and mediastinal disorders Dyspnoea	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Respiratory, thoracic and mediastinal disorders Hypoventilation	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Respiratory, thoracic and mediastinal disorders Laryngospasm	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Vascular disorders Peripheral ischaemia	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	6.7% 2/30 • Number of events 2 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Vascular disorders Aortic stenosis	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Vascular disorders Hypertension	20.0% 1/5 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Vascular disorders Hypotension	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/7 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	7.7% 1/13 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.
Vascular disorders Peripheral coldness	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	14.3% 1/7 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/5 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	0.00% 0/13 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.	3.3% 1/30 • Number of events 1 • Adverse events were recorded from start of study up to the end of trial on Day 28, or end of follow-up period as applicable. Collection of adverse events comprised the patient's positive response to questions about their health, symptoms spontaneously reported by the patient, and clinically relevant changes and abnormalities observed by the investigator.

Additional Information

Clinical Development Support

Ferring Pharmaceuticals

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
Publication restrictions are in place

Restriction type: OTHER