Trial Outcomes & Findings for AZD9773 Dose Escalation Study (NCT NCT00615017)
NCT ID: NCT00615017
Last Updated: 2013-08-22
Results Overview
Change in creatinine values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) \[calculated as Day 28 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
70 participants
Primary outcome timeframe
End of study (Day 28)
Results posted on
2013-08-22
Participant Flow
The first patient was enrolled on January 18, 2008 and the last patient had their last visit on July 30, 2009. Patients were randomised at 17 centres in the United States of America
70 adult patients with severe sepsis, clinical evidence of infection requiring parenteral antibiotics, meeting systemic inflammatory response syndrome criteria, and with cardiovascular/respiratory dysfunction were randomised to receive AZD9773 (2 single dose and 3 multiple dose cohorts) in a double-blind, placebo controlled, dose escalation study
Participant milestones
| Measure |
AZD9773 Cohort 5 (750/250 Units/kg)
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
AZD9773: single infusion of 50 units/kg
|
AZD9773 Cohort 2 (250 Units/kg)
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
23
|
8
|
9
|
12
|
10
|
|
Overall Study
COMPLETED
|
7
|
20
|
8
|
8
|
7
|
9
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
0
|
1
|
5
|
1
|
Reasons for withdrawal
| Measure |
AZD9773 Cohort 5 (750/250 Units/kg)
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
AZD9773: single infusion of 50 units/kg
|
AZD9773 Cohort 2 (250 Units/kg)
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
1
|
2
|
0
|
|
Overall Study
Death
|
1
|
1
|
0
|
0
|
2
|
0
|
|
Overall Study
Sepsis resolved
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Transferred out of Intensive Care Unit
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Physician discontinued drug
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
AZD9773 Dose Escalation Study
Baseline characteristics by cohort
| Measure |
AZD9773 Cohort 1 (50 Units/kg)
n=8 Participants
AZD9773: single infusion of 50 units/kg
|
AZD9773 Cohort 2 (250 Units/kg)
n=9 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=12 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=10 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=8 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=23 Participants
Placebo
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age Continuous
|
53 Year
STANDARD_DEVIATION 11.8 • n=5 Participants
|
49.7 Year
STANDARD_DEVIATION 15 • n=7 Participants
|
55.1 Year
STANDARD_DEVIATION 10.8 • n=5 Participants
|
53 Year
STANDARD_DEVIATION 17.9 • n=4 Participants
|
63.5 Year
STANDARD_DEVIATION 16.1 • n=21 Participants
|
58.9 Year
STANDARD_DEVIATION 17.4 • n=8 Participants
|
56.1 Year
STANDARD_DEVIATION 15.5 • n=8 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
12 Participants
n=8 Participants
|
38 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
11 Participants
n=8 Participants
|
32 Participants
n=8 Participants
|
|
Mechanical ventilation
Yes
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
20 Participants
n=8 Participants
|
60 Participants
n=8 Participants
|
|
Mechanical ventilation
No
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
7 Participants
n=8 Participants
|
|
Mechanical ventilation
Missing
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
|
Organ failure site
Cardiovascular
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
7 Participants
n=8 Participants
|
19 Participants
n=8 Participants
|
|
Organ failure site
Pulmonary dysfunction
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
13 Participants
n=8 Participants
|
|
Organ failure site
Cardiovascular and pulmonary dysfunction
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
13 Participants
n=8 Participants
|
38 Participants
n=8 Participants
|
|
Shock
Yes
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
20 Participants
n=8 Participants
|
56 Participants
n=8 Participants
|
|
Shock
No
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
14 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: End of study (Day 28)Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in creatinine values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) \[calculated as Day 28 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=4 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=7 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=8 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=6 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=15 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=5 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Creatinine Values
|
-196.8 μmol/L
Full Range -681 • Interval -681.0 to 0.0
|
-25.1 μmol/L
Full Range -126 • Interval -126.0 to 44.0
|
-10.9 μmol/L
Full Range -68 • Interval -68.0 to 167.0
|
159.0 μmol/L
Full Range -89 • Interval -89.0 to 1087.0
|
-57.4 μmol/L
Full Range -191 • Interval -191.0 to 18.0
|
-78.6 μmol/L
Full Range -239 • Interval -239.0 to 8.0
|
PRIMARY outcome
Timeframe: End of study (Day 28)Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in alanine aminotransferase values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) \[calculated as Day 28 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=3 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=7 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=7 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=6 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=15 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=5 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Alanine Aminotransferase Values
|
0.017 μkat/L
Full Range -0.25 • Interval -0.25 to 0.43
|
-3.133 μkat/L
Full Range -20.62 • Interval -20.62 to -0.03
|
-0.520 μkat/L
Full Range -2.05 • Interval -2.05 to 0.0
|
-0.825 μkat/L
Full Range -4.53 • Interval -4.53 to 0.38
|
-0.111 μkat/L
Full Range -0.79 • Interval -0.79 to 0.2
|
-0.998 μkat/L
Full Range -3.24 • Interval -3.24 to 0.16
|
PRIMARY outcome
Timeframe: End of study (Day 28)Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in aspartate aminotransferase values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) \[calculated as Day 28 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=3 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=7 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=7 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=6 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=15 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=5 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Aspartate Aminotransferase Values
|
-0.213 μkat/L
Full Range -0.43 • Interval -0.43 to 0.15
|
-3.647 μkat/L
Full Range -21.36 • Interval -21.36 to -0.02
|
-0.926 μkat/L
Full Range -3.27 • Interval -3.27 to 0.2
|
-0.998 μkat/L
Full Range -3.29 • Interval -3.29 to 0.11
|
-0.253 μkat/L
Full Range -1.54 • Interval -1.54 to 0.15
|
-2.298 μkat/L
Full Range -5.56 • Interval -5.56 to -0.04
|
PRIMARY outcome
Timeframe: End of study (Day 28)Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in bilirubin values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) \[calculated as Day 28 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=3 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=7 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=7 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=6 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=15 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=5 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Bilirubin Values
|
-13.10 μmol/L
Full Range -34.2 • Interval -34.2 to 0.0
|
-10.04 μmol/L
Full Range -49.6 • Interval -49.6 to 0.0
|
-23.71 μmol/L
Full Range -71.8 • Interval -71.8 to 0.0
|
-2.58 μmol/L
Full Range -29.1 • Interval -29.1 to 30.8
|
-10.00 μmol/L
Full Range -37.6 • Interval -37.6 to 4.2
|
-11.30 μmol/L
Full Range -17.1 • Interval -17.1 to -5.2
|
PRIMARY outcome
Timeframe: End of study (Day 28)Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in haemoglobin values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) \[calculated as Day 28 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=4 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=6 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=4 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=5 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=13 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=5 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Haemoglobin Values
|
-16.3 g/L
Full Range -42 • Interval -42.0 to 21.0
|
-0.8 g/L
Full Range -31 • Interval -31.0 to 33.0
|
6.5 g/L
Full Range -5 • Interval -5.0 to 17.0
|
-13.8 g/L
Full Range -35 • Interval -35.0 to 4.0
|
-4.5 g/L
Full Range -47 • Interval -47.0 to 32.0
|
7 g/L
Full Range -18 • Interval -18.0 to 31.0
|
PRIMARY outcome
Timeframe: End of study (Day 28)Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in white blood cell values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) \[calculated as Day 28 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=4 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=6 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=4 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=5 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=13 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=5 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in White Blood Cell Values
|
-8.975 10^9 cells/L
Full Range -22.58 • Interval -22.58 to 2.18
|
0.413 10^9 cells/L
Full Range -8.11 • Interval -8.11 to 14.84
|
-0.225 10^9 cells/L
Full Range -5.60 • Interval -5.6 to 2.86
|
-3.482 10^9 cells/L
Full Range -13.42 • Interval -13.42 to 5.82
|
-9.987 10^9 cells/L
Full Range -26.40 • Interval -26.4 to 3.34
|
-17.552 10^9 cells/L
Full Range -46.67 • Interval -46.67 to -6.11
|
PRIMARY outcome
Timeframe: End of study (Day 28)Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in platelet count values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) \[calculated as Day 28 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=3 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=5 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=4 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=4 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=13 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=5 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Platelet Count Values
|
117.3 10^9/L
Full Range 18 • Interval 18.0 to 176.0
|
162 10^9/L
Full Range -56 • Interval -56.0 to 474.0
|
72.3 10^9/L
Full Range -114 • Interval -114.0 to 159.0
|
252.5 10^9/L
Full Range 40 • Interval 40.0 to 591.0
|
145.1 10^9/L
Full Range -232 • Interval -232.0 to 735.0
|
287 10^9/L
Full Range -41 • Interval -41.0 to 650.0
|
PRIMARY outcome
Timeframe: Day 7Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in prothrombin time values from baseline (pre-infusion) to Day 7 \[calculated as Day 7 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=4 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=6 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=7 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=5 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=17 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=5 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Prothrombin Time Values
|
0.53 sec
Full Range -0.8 • Interval -0.8 to 2.2
|
-1.00 sec
Full Range -2.4 • Interval -2.4 to 0.0
|
-5.31 sec
Full Range -14.7 • Interval -14.7 to 0.4
|
4.36 sec
Full Range -23.8 • Interval -23.8 to 49.4
|
1.68 sec
Full Range -7.5 • Interval -7.5 to 32.0
|
-3.20 sec
Full Range -8.6 • Interval -8.6 to 2.2
|
PRIMARY outcome
Timeframe: Day 6Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in troponin I values from baseline (pre-infusion) to Day 6 \[calculated as Day 6 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=3 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=4 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=9 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=3 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=19 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=8 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Troponin I
|
-9.523 μg/L
Full Range -28.58 • Interval -28.58 to 0.01
|
-0.630 μg/L
Full Range -1.61 • Interval -1.61 to 0.1
|
-1.434 μg/L
Full Range -7.21 • Interval -7.21 to 0.04
|
-0.027 μg/L
Full Range -0.07 • Interval -0.07 to 0.0
|
-0.735 μg/L
Full Range -6.77 • Interval -6.77 to 3.68
|
-16.454 μg/L
Full Range -127.37 • Interval -127.37 to 0.26
|
PRIMARY outcome
Timeframe: Day 1 (end of infusion) for Cohorts 1 and 2; Day 5 (end of infusion) for Cohorts 3 to 5 and placeboPopulation: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in QTcF from baseline (pre-infusion) to Day 1 (end of infusion) for Cohorts 1 and 2 \[calculated as Day 1 mean minus baseline mean\] and Day 5 (end of infusion) for Cohorts 3 to 5 and placebo \[calculated as Day 5 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=9 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=6 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=9 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=6 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=13 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=7 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in QT With Fridericia Correction (QTcF), Where QT is Measured by ECG, and is the Time Interval Between the Start of the Q Wave and the End of the T Wave in the Heart's Electrical Cycle.
|
3.6 msec
Full Range -35 • Interval -35.0 to 63.0
|
-21.5 msec
Full Range -43 • Interval -43.0 to -1.0
|
-9.2 msec
Full Range -47 • Interval -47.0 to 44.0
|
21.4 msec
Full Range -32 • Interval -32.0 to 66.0
|
-3.4 msec
Full Range -61 • Interval -61.0 to 29.0
|
-9.9 msec
Full Range -37 • Interval -37.0 to 9.0
|
PRIMARY outcome
Timeframe: Day 14Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in calculated mean arterial pressure from baseline (pre-infusion) to Day 14 \[calculated as Day 14 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=6 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=4 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=6 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=5 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=11 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=3 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Calculated Mean Arterial Blood Pressure
|
7.3 mmHg
Full Range 2 • Interval 2.0 to 13.0
|
5.3 mmHg
Full Range -19 • Interval -19.0 to 34.0
|
28.7 mmHg
Full Range 4 • Interval 4.0 to 65.0
|
6.8 mmHg
Full Range -9 • Interval -9.0 to 22.0
|
18 mmHg
Full Range -4 • Interval -4.0 to 44.0
|
20 mmHg
Full Range 3 • Interval 3.0 to 32.0
|
PRIMARY outcome
Timeframe: Day 6Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in body weight from baseline (pre-infusion) to Day 6 \[calculated as Day 6 mean minus baseline mean\]. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=6 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=3 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=5 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=5 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=12 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=7 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Body Weight
|
0.2 kg
Full Range -7 • Interval -7.0 to 10.0
|
4 kg
Full Range 1 • Interval 1.0 to 8.0
|
7.4 kg
Full Range -10 • Interval -10.0 to 25.0
|
0.2 kg
Full Range -11 • Interval -11.0 to 14.0
|
9.9 kg
Full Range 0 • Interval 0.0 to 35.0
|
1.3 kg
Full Range -2 • Interval -2.0 to 9.0
|
SECONDARY outcome
Timeframe: End of study (Day 28)The number of patients who had died at Day 28. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=9 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=12 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=10 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=8 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=23 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=8 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
28-Day Mortality
|
4 Participants
|
5 Participants
|
1 Participants
|
1 Participants
|
6 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Day 6Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Change in SOFA (Sequential Organ Failure Assessment) scores from baseline (pre-infusion) to Day 6 \[calculated as Day 6 mean minus baseline mean\]. The SOFA score is out of a maximum of 24 (units on a scale 0 to 24). The higher the score, the worse the organ system functioning. Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=3 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=3 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=6 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=3 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=9 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=2 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Sequential Organ Failure Assessment (SOFA) Scores
|
-2 units on a scale (0 to 24)
Full Range -5 • Interval -5.0 to 0.0
|
-3.3 units on a scale (0 to 24)
Full Range -5 • Interval -5.0 to -2.0
|
-3 units on a scale (0 to 24)
Full Range -7 • Interval -7.0 to 7.0
|
-6 units on a scale (0 to 24)
Full Range -11 • Interval -11.0 to -2.0
|
-4.3 units on a scale (0 to 24)
Full Range -8 • Interval -8.0 to 2.0
|
-6 units on a scale (0 to 24)
Full Range -7 • Interval -7.0 to -5.0
|
SECONDARY outcome
Timeframe: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, and 12h post-(last) infusion]Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
AUC(0-12) for single dose AZD9773 serum total Fabs (cohorts 1 and 2). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=8 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=7 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Area Under the Serum Concentration-time Curve From 0 to 12 Hours (AUC(0-12)) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
|
581.01 μg.h/mL
Interval 197.6 to 1561.8
|
—
|
—
|
—
|
—
|
125.22 μg.h/mL
Interval 68.6 to 545.3
|
SECONDARY outcome
Timeframe: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
t1/2 of single dose AZD9773 serum total Fabs (cohorts 1 and 2). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=6 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=7 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Terminal Half-life (t1/2) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
|
19.76 Hours
Full Range 10.5 • Interval 10.5 to 25.6
|
—
|
—
|
—
|
—
|
17.97 Hours
Full Range 7.8 • Interval 7.8 to 30.1
|
SECONDARY outcome
Timeframe: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
CL of single dose AZD9773 serum total Fabs (cohorts 1 and 2). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=6 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=7 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Total Apparent Clearance (CL) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
|
7.61 mL/min/kg
Full Range 0.8 • Interval 0.8 to 16.7
|
—
|
—
|
—
|
—
|
6.11 mL/min/kg
Full Range 1.2 • Interval 1.2 to 11.5
|
SECONDARY outcome
Timeframe: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last) infusion]Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
AUC(0-12) of loading dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=8 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=9 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=5 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
AUC(0-12) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
|
—
|
449.18 μg.h/mL
Interval 230.2 to 828.8
|
691.53 μg.h/mL
Interval 474.6 to 1024.7
|
1872.73 μg.h/mL
Interval 1391.2 to 2559.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
Cinf of loading dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=8 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=9 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=5 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Maximum (End of Infusion) Serum Concentration (Cinf) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3,4 and 5)
|
—
|
107.84 μg/mL
Interval 72.3 to 197.0
|
160.09 μg/mL
Interval 130.0 to 208.0
|
351.52 μg/mL
Interval 286.0 to 443.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]Population: Participants analyzed relates to the number of evaluable patients at the specified time point.
tmax of loading dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=8 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=9 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=5 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Time to Reach Cinf (Tmax) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
|
—
|
0.92 Hours
Interval 0.5 to 1.4
|
1.08 Hours
Interval 0.9 to 1.7
|
1.12 Hours
Interval 1.1 to 1.3
|
—
|
—
|
SECONDARY outcome
Timeframe: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusionPopulation: Participants analyzed relates to the number of evaluable patients at the specified time point.
AUC(0-12) of maintenance dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=6 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=7 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=4 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
AUC(0-12) of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
|
—
|
162.82 μg.h/mL
Interval 66.3 to 440.4
|
251.59 μg.h/mL
Interval 102.4 to 531.7
|
980.95 μg.h/mL
Interval 646.0 to 1524.2
|
—
|
—
|
SECONDARY outcome
Timeframe: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusionPopulation: Participants analyzed relates to the number of evaluable patients at the specified time point.
Cinf of maintenance dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=6 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=7 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=4 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Cinf of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
|
—
|
28.37 μg/mL
Interval 14.6 to 58.4
|
42.51 μg/mL
Interval 8.9 to 71.1
|
151.76 μg/mL
Interval 129.0 to 184.0
|
—
|
—
|
SECONDARY outcome
Timeframe: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusionPopulation: Participants analyzed relates to the number of evaluable patients at the specified time point.
tmax of maintenance dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=6 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=7 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=4 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Tmax of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
|
—
|
0.54 Hours
Interval 0.0 to 0.7
|
1.00 Hours
Interval 0.4 to 8.5
|
0.74 Hours
Interval 0.5 to 1.6
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 hoursPopulation: Participants analyzed relates to the number of evaluable patients at the specified time point.
Number of patients below tumour necrosis factor (TNF)-alpha limit of quantification (LOQ) at 24 hours (n\< LOQ) measured by ELISA (LOQ = 1.3 pg/mL). Safety analysis set (ie all patients who started study drug infusion).
Outcome measures
| Measure |
AZD9773 Cohort 2 (250 Units/kg)
n=9 Participants
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=10 Participants
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=9 Participants
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=5 Participants
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=22 Participants
Placebo
|
AZD9773 Cohort 1 (50 Units/kg)
n=7 Participants
AZD9773: single infusion of 50 units/kg
|
|---|---|---|---|---|---|---|
|
Number of Patients Below Tumour Necrosis Factor (TNF)-Alpha Limit of Quantification (LOQ) at 24 Hours (n< LOQ)
|
3.0 Participants
|
5.0 Participants
|
6.0 Participants
|
4.0 Participants
|
0.0 Participants
|
1.0 Participants
|
Adverse Events
AZD9773 Cohort 1 (50 Units/kg)
Serious events: 3 serious events
Other events: 8 other events
Deaths: 0 deaths
AZD9773 Cohort 2 (250 Units/kg)
Serious events: 6 serious events
Other events: 8 other events
Deaths: 0 deaths
AZD9773 Cohort 3 (250/50 Units/kg)
Serious events: 7 serious events
Other events: 11 other events
Deaths: 0 deaths
AZD9773 Cohort 4 (500/100 Units/kg)
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
AZD9773 Cohort 5 (750/250 Units/kg)
Serious events: 4 serious events
Other events: 7 other events
Deaths: 0 deaths
Placebo
Serious events: 13 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AZD9773 Cohort 1 (50 Units/kg)
n=8 participants at risk
AZD9773: single infusion of 50 units/kg
|
AZD9773 Cohort 2 (250 Units/kg)
n=9 participants at risk
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=12 participants at risk
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=10 participants at risk
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=8 participants at risk
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=23 participants at risk
Placebo
|
|---|---|---|---|---|---|---|
|
Infections and infestations
Sepsis
|
12.5%
1/8 • Number of events 1
|
0.00%
0/9
|
25.0%
3/12 • Number of events 3
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
12.5%
1/8 • Number of events 1
|
11.1%
1/9 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
0.00%
0/8
|
13.0%
3/23 • Number of events 3
|
|
Infections and infestations
Septic Shock
|
0.00%
0/8
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8 • Number of events 1
|
8.7%
2/23 • Number of events 2
|
|
Infections and infestations
Empyema
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Endocarditis
|
0.00%
0/8
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Cellulitis
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8 • Number of events 1
|
4.3%
1/23 • Number of events 2
|
|
Cardiac disorders
Cardiac Arrest
|
12.5%
1/8 • Number of events 1
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23 • Number of events 2
|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10 • Number of events 1
|
0.00%
0/8
|
4.3%
1/23 • Number of events 1
|
|
Cardiac disorders
Cardiac Failure
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Cardiac disorders
Supraventricular Tachycardia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10 • Number of events 1
|
0.00%
0/8
|
8.7%
2/23 • Number of events 2
|
|
Cardiac disorders
Atrial Fibrillation
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10 • Number of events 1
|
0.00%
0/8
|
17.4%
4/23 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.00%
0/8
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8 • Number of events 1
|
4.3%
1/23 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
20.0%
2/10 • Number of events 2
|
0.00%
0/8
|
13.0%
3/23 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia Aspiration
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10 • Number of events 1
|
0.00%
0/8
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23 • Number of events 2
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/8
|
4.3%
1/23 • Number of events 1
|
|
Vascular disorders
Shock
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Vascular disorders
Shock Haemorrhagic
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23 • Number of events 1
|
|
Vascular disorders
Peripheral Ischaemia
|
0.00%
0/8
|
0.00%
0/9
|
16.7%
2/12 • Number of events 2
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23 • Number of events 1
|
|
Gastrointestinal disorders
Enterocutaneous Fistula
|
0.00%
0/8
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8 • Number of events 1
|
0.00%
0/23
|
|
Gastrointestinal disorders
Intestinal Ischaemia
|
0.00%
0/8
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8 • Number of events 1
|
4.3%
1/23 • Number of events 1
|
|
Gastrointestinal disorders
Intestinal Perforation
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23 • Number of events 1
|
|
Injury, poisoning and procedural complications
Medical Device Complication
|
0.00%
0/8
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Metabolism and nutrition disorders
Acidosis
|
0.00%
0/8
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Neoplasm Malignant
|
0.00%
0/8
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Nervous system disorders
Cerebral Infarction
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Nervous system disorders
Haemorrhage Intracranial
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Toxic Epidermal Necrolysis
|
12.5%
1/8 • Number of events 1
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Musculoskeletal and connective tissue disorders
Muscle Haemorrhage
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23 • Number of events 1
|
Other adverse events
| Measure |
AZD9773 Cohort 1 (50 Units/kg)
n=8 participants at risk
AZD9773: single infusion of 50 units/kg
|
AZD9773 Cohort 2 (250 Units/kg)
n=9 participants at risk
AZD9773: single infusion of 250 units/kg
|
AZD9773 Cohort 3 (250/50 Units/kg)
n=12 participants at risk
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
|
AZD9773 Cohort 4 (500/100 Units/kg)
n=10 participants at risk
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
|
AZD9773 Cohort 5 (750/250 Units/kg)
n=8 participants at risk
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
|
Placebo
n=23 participants at risk
Placebo
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
12.5%
1/8 • Number of events 1
|
33.3%
3/9 • Number of events 3
|
16.7%
2/12 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
25.0%
2/8 • Number of events 3
|
17.4%
4/23 • Number of events 4
|
|
Blood and lymphatic system disorders
Hypercoagulation
|
12.5%
1/8 • Number of events 1
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8 • Number of events 1
|
0.00%
0/23
|
|
Blood and lymphatic system disorders
Leucocytosis
|
12.5%
1/8 • Number of events 1
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
10.0%
1/10 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
8.7%
2/23 • Number of events 2
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
12.5%
1/8 • Number of events 1
|
0.00%
0/9
|
16.7%
2/12 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
8.7%
2/23 • Number of events 2
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/8
|
0.00%
0/9
|
16.7%
2/12 • Number of events 2
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23 • Number of events 1
|
|
Blood and lymphatic system disorders
Heparin-Induced Thrombocytopenia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10 • Number of events 1
|
0.00%
0/8
|
4.3%
1/23 • Number of events 1
|
|
Blood and lymphatic system disorders
Thrombocythaemia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
13.0%
3/23 • Number of events 3
|
|
Cardiac disorders
Atrial Flutter
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
4.3%
1/23
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
20.0%
2/10
|
0.00%
0/8
|
13.0%
3/23
|
|
Cardiac disorders
Bundle Branch Block Right
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Cardiac disorders
Supraventricular Tachycardia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Cardiac disorders
Ventricular Tachycardia
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Endocrine disorders
Adrenal Insufficiency
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Eye disorders
Conjunctivitis
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Eye disorders
Scleral Haemorrhage
|
25.0%
2/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Eye disorders
Scleral Oedema
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Gastrointestinal disorders
Abdominal Compartment Syndrome
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
2/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
12.5%
1/8
|
17.4%
4/23
|
|
Gastrointestinal disorders
Gastric Ulcer
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
4.3%
1/23
|
|
Gastrointestinal disorders
Nausea
|
12.5%
1/8
|
11.1%
1/9
|
8.3%
1/12
|
10.0%
1/10
|
12.5%
1/8
|
13.0%
3/23
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Gastrointestinal disorders
Constipation
|
25.0%
2/8
|
22.2%
2/9
|
16.7%
2/12
|
10.0%
1/10
|
0.00%
0/8
|
26.1%
6/23
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Gastrointestinal disorders
Dysphagia
|
12.5%
1/8
|
0.00%
0/9
|
8.3%
1/12
|
10.0%
1/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Gastrointestinal disorders
Gastrointestinal Motility Disorder
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Gastrointestinal disorders
Intestinal Ischaemia
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
4.3%
1/23
|
|
Gastrointestinal disorders
Rectal Haemorrhage
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Gastrointestinal disorders
Salivary Hypersecretion
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
2/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
General disorders
General Oedema
|
0.00%
0/8
|
11.1%
1/9
|
25.0%
3/12
|
20.0%
2/10
|
37.5%
3/8
|
13.0%
3/23
|
|
General disorders
Asthenia
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
12.5%
1/8
|
4.3%
1/23
|
|
General disorders
Hypothermia
|
0.00%
0/8
|
0.00%
0/9
|
16.7%
2/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
General disorders
Oedema Periheral
|
25.0%
2/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
17.4%
4/23
|
|
General disorders
Chest Pain
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
General disorders
Chills
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
General disorders
Face Oedema
|
0.00%
0/8
|
0.00%
0/9
|
16.7%
2/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
General disorders
Multi-Organ Failure
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
General disorders
Pain
|
12.5%
1/8
|
0.00%
0/9
|
8.3%
1/12
|
10.0%
1/10
|
0.00%
0/8
|
17.4%
4/23
|
|
General disorders
Pyrexia
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
4.3%
1/23
|
|
Hepatobiliary disorders
Ischaemic Hepatitis
|
12.5%
1/8
|
0.00%
0/9
|
8.3%
1/12
|
10.0%
1/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Infections and infestations
Enterobacter Pneumonia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Infections and infestations
Infected Skin Ulcer
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Infections and infestations
Pelvic Abscess
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Infections and infestations
Sinusitis
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Infections and infestations
Systemic Candida
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Infections and infestations
Tracheobronchitis
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Infections and infestations
Urinary Tract Infection Enterococcal
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Candiduria
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Central Line Infection
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Clostridial Infection
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Clostridium Difficile Colitis
|
0.00%
0/8
|
11.1%
1/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Infections and infestations
Escherichia Urinary Tract Infection
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Fungal Skin Infection
|
12.5%
1/8
|
11.1%
1/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Gangrene
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Herpes Simplex
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Lung Infection Pseudomonal
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Oral Herpes
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Infections and infestations
Pneumonia Bacterial
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
10.0%
1/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Infections and infestations
Pneumonia Escherichia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Pneumonia Staphylococcal
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Infections and infestations
Urinary Tract Infection
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Infections and infestations
Vulvovaginal Mycotic Infection
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Injury, poisoning and procedural complications
Bloody Airway Discharge
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Injury, poisoning and procedural complications
Procedural Hypotension
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Injury, poisoning and procedural complications
Endotracheal Intubation Complication
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Injury, poisoning and procedural complications
Excoriation
|
12.5%
1/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Injury, poisoning and procedural complications
Gastrointestinal Stoma Complication
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Injury, poisoning and procedural complications
Skin Laceration
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Investigations
Airway Peak Pressure Increased
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Investigations
Blood Albumin Decreased
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Investigations
Blood Alkaline Phosphatase Decreased
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Investigations
Blood Phosphorus Decreased
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Investigations
Blood Sodium Decreased
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Investigations
Aspartate Aminotransferase Increased
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Investigations
Blood Creatine Phosphokinase Increased
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Investigations
Blood Lactate Dehydrogenase Increased
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Investigations
Brain Natriuretic Peptide Increased
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Investigations
Breath Sounds Abnormal
|
0.00%
0/8
|
11.1%
1/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Investigations
Clostridium Difficile Toxin Test Positive
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Investigations
Ejection Fraction Decreased
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Investigations
Fibrin D Dimer Increased
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Investigations
Haemoglobin Decreased
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Investigations
Hepatic Enzyme Increased
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Investigations
Oxygen Saturation Decreased
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Investigations
Troponin Increased
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Investigations
Urinary Sediment Present
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Investigations
Urine Output Decreased
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
12.5%
1/8
|
11.1%
1/9
|
8.3%
1/12
|
40.0%
4/10
|
37.5%
3/8
|
8.7%
2/23
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
12.5%
1/8
|
11.1%
1/9
|
0.00%
0/12
|
30.0%
3/10
|
25.0%
2/8
|
8.7%
2/23
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
8.7%
2/23
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
25.0%
2/8
|
11.1%
1/9
|
0.00%
0/12
|
20.0%
2/10
|
12.5%
1/8
|
8.7%
2/23
|
|
Metabolism and nutrition disorders
Feeding Disorder
|
12.5%
1/8
|
22.2%
2/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Metabolism and nutrition disorders
Fluid Overload
|
0.00%
0/8
|
22.2%
2/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
25.0%
2/8
|
11.1%
1/9
|
0.00%
0/12
|
20.0%
2/10
|
0.00%
0/8
|
30.4%
7/23
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/8
|
11.1%
1/9
|
16.7%
2/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Metabolism and nutrition disorders
Lactic Acidosis
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Metabolism and nutrition disorders
Metabolic Acidosis
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Nervous system disorders
Aphasia
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Nervous system disorders
Convulsion
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Nervous system disorders
Depressed Level Of Consciousness
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Nervous system disorders
Headache
|
12.5%
1/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Nervous system disorders
Unresponsive To Stimuli
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Psychiatric disorders
Agitation
|
25.0%
2/8
|
22.2%
2/9
|
8.3%
1/12
|
30.0%
3/10
|
12.5%
1/8
|
17.4%
4/23
|
|
Psychiatric disorders
Anxiety
|
12.5%
1/8
|
0.00%
0/9
|
16.7%
2/12
|
0.00%
0/10
|
12.5%
1/8
|
8.7%
2/23
|
|
Psychiatric disorders
Confusional State
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Psychiatric disorders
Depression
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Psychiatric disorders
Hallucination
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Psychiatric disorders
Insomnia
|
12.5%
1/8
|
22.2%
2/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Psychiatric disorders
Mental Status Changes
|
12.5%
1/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Renal and urinary disorders
Renal Failure Acute
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Renal and urinary disorders
Renal Failure
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Renal and urinary disorders
Renal Impairment
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Reproductive system and breast disorders
Scrotal Oedema
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
8.7%
2/23
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Lung Disorder
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
13.0%
3/23
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Congestion
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Oedema
|
12.5%
1/8
|
11.1%
1/9
|
8.3%
1/12
|
10.0%
1/10
|
0.00%
0/8
|
13.0%
3/23
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Alkalosis
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Distress
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Rhonchi
|
12.5%
1/8
|
11.1%
1/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
12.5%
1/8
|
22.2%
2/9
|
0.00%
0/12
|
10.0%
1/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Skin and subcutaneous tissue disorders
Decubitus Ulcer
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
20.0%
2/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Drug Eruption
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
12.5%
1/8
|
26.1%
6/23
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.5%
1/8
|
0.00%
0/9
|
8.3%
1/12
|
10.0%
1/10
|
12.5%
1/8
|
8.7%
2/23
|
|
Skin and subcutaneous tissue disorders
Rash Maculo-Papular
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Skin Discolouration
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Skin Disorder
|
0.00%
0/8
|
11.1%
1/9
|
8.3%
1/12
|
10.0%
1/10
|
12.5%
1/8
|
8.7%
2/23
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
4.3%
1/23
|
|
Skin and subcutaneous tissue disorders
Periorbital Oedema
|
12.5%
1/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/8
|
0.00%
0/9
|
8.3%
1/12
|
0.00%
0/10
|
0.00%
0/8
|
0.00%
0/23
|
|
Vascular disorders
Hypertension
|
0.00%
0/8
|
11.1%
1/9
|
0.00%
0/12
|
20.0%
2/10
|
12.5%
1/8
|
0.00%
0/23
|
|
Vascular disorders
Hypotension
|
0.00%
0/8
|
11.1%
1/9
|
16.7%
2/12
|
10.0%
1/10
|
12.5%
1/8
|
8.7%
2/23
|
|
Vascular disorders
Peripheral Coldness
|
0.00%
0/8
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/10
|
12.5%
1/8
|
0.00%
0/23
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60