AZD9773 Dose Escalation Study
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT00615017
Collaborator
(none)
70
26
6
18
2.7
0.1
Study Details
Study Description
Brief Summary
This is a double-blind, placebo-controlled, multi-center, dose-escalation study to assess the safety, tolerability, Pharmacokinetics and Pharmacodynamics of single and multiple ascending intravenous infusions of CytoFab (AZD9773) in adult patients with severe sepsis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
70 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Placebo-controlled, Double-blind, Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics and Pharmacodynamics of Single and Multiple Intravenous Infusions of CytoFab (AZD9773) in Patients With Severe Sepsis
Study Start Date
:
Jan 1, 2008
Actual Primary Completion Date
:
Jul 1, 2009
Actual Study Completion Date
:
Jul 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AZD9773 cohort 1 (50 units/kg) AZD9773: single infusion of 50 units/kg |
Drug: AZD9773 (CytoFab)
intravenous infusions
|
| Experimental: AZD9773 cohort 2 (250 units/kg) AZD9773: single infusion of 250 units/kg |
Drug: AZD9773 (CytoFab)
intravenous infusions
|
| Experimental: AZD9773 cohort 3 (250/50 units/kg) AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs |
Drug: AZD9773 (CytoFab)
intravenous infusions
|
| Experimental: AZD9773 cohort 4 (500/100 units/kg) AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs |
Drug: AZD9773 (CytoFab)
intravenous infusions
|
| Experimental: AZD9773 cohort 5 (750/250 units/kg) AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs |
Drug: AZD9773 (CytoFab)
intravenous infusions
|
| Placebo Comparator: Placebo Placebo |
Other: Placebo
Placebo
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Creatinine Values [End of study (Day 28)]
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).
- Change From Baseline in Alanine Aminotransferase Values [End of study (Day 28)]
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).
- Change From Baseline in Aspartate Aminotransferase Values [End of study (Day 28)]
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).
- Change From Baseline in Bilirubin Values [End of study (Day 28)]
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).
- Change From Baseline in Haemoglobin Values [End of study (Day 28)]
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).
- Change From Baseline in White Blood Cell Values [End of study (Day 28)]
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).
- Change From Baseline in Platelet Count Values [End of study (Day 28)]
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).
- Change From Baseline in Prothrombin Time Values [Day 7]
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).
- Change From Baseline in Troponin I [Day 6]
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).
- 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. [Day 1 (end of infusion) for Cohorts 1 and 2; Day 5 (end of infusion) for Cohorts 3 to 5 and placebo]
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).
- Change From Baseline in Calculated Mean Arterial Blood Pressure [Day 14]
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).
- Change From Baseline in Body Weight [Day 6]
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).
Secondary Outcome Measures
- 28-Day Mortality [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).
- Change From Baseline in Sequential Organ Failure Assessment (SOFA) Scores [Day 6]
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).
- 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) [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]]
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).
- Terminal Half-life (t1/2) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2) [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]]
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).
- Total Apparent Clearance (CL) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2) [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]]
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).
- AUC(0-12) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) [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]]
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).
- Maximum (End of Infusion) Serum Concentration (Cinf) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3,4 and 5) [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]]
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).
- Time to Reach Cinf (Tmax) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) [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]]
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).
- AUC(0-12) of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) [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 infusion]
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).
- Cinf of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) [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 infusion]
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).
- Tmax of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) [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 infusion]
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).
- Number of Patients Below Tumour Necrosis Factor (TNF)-Alpha Limit of Quantification (LOQ) at 24 Hours (n< LOQ) [24 hours]
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).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Clinical evidence of infection requiring treatment with parenteral antibiotics
-
Patients must meet multiple Systemic Inflammatory Response Syndrome (SIRS) criteria
-
Patients must meet criteria for cardiovascular and/or respiratory dysfunction
-
Sepsis (infection plus SIRS criteria) must be present prior to organ dysfunction
Exclusion Criteria:
-
Moribund and death is considered imminent, or patient not expected to survive 90 days because of underlying medical condition, or classified as Do Not Resuscitate or Do Not Treat
-
Patient cannot attain a MAP >60 mmHg when measured via an arterial line and/or a Systolic Blood Pressure (SBP) >80 mmHg in the presence of vasopressors and iv fluids for a period of ≥2 hours
-
Receiving immunosuppressants, or high dose steroids within 2 months of provision of informed consent
-
Any history of hypersensitivity reaction to sheep products, latex, papain or papaya, or chymopapain or previously administered antivenom manufactured using ovine serum, digoxin immune fab (DigiFab™ , DIGIBIND® ), crotalidae polyvalent immune fab (ovine) (CroFab™ ), or other sheep derived product.
-
Treatment with anti Tumor-Necrosis-Factor (anti-TNF) antibodies within 8 weeks before provision of written informed consent.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Birmingham | Alabama | United States | |
| 2 | Research Site | Newark | Delaware | United States | |
| 3 | Research Site | Bay Pines | Florida | United States | |
| 4 | Research Site | Miami | Florida | United States | |
| 5 | Research Site | Chicago | Illinois | United States | |
| 6 | Research Site | Oak Park | Illinois | United States | |
| 7 | Research Site | Peoria | Illinois | United States | |
| 8 | Research Site | Indianapolis | Indiana | United States | |
| 9 | Research Site | Iowa City | Iowa | United States | |
| 10 | Research Site | Hazard | Kentucky | United States | |
| 11 | Research Site | Lexington | Kentucky | United States | |
| 12 | Research Site | Baltimore | Maryland | United States | |
| 13 | Research Site | Kansas City | Missouri | United States | |
| 14 | Research Site | Camden | New Jersey | United States | |
| 15 | Research Site | Newark | New Jersey | United States | |
| 16 | Research Site | Brooklyn | New York | United States | |
| 17 | Research Site | New York | New York | United States | |
| 18 | Research Site | Rochester | New York | United States | |
| 19 | Research Site | Durham | North Carolina | United States | |
| 20 | Research Site | Greensboro | North Carolina | United States | |
| 21 | Research Site | Winston Salem | North Carolina | United States | |
| 22 | Research Site | Columbus | Ohio | United States | |
| 23 | Research Site | Oklahoma City | Oklahoma | United States | |
| 24 | Research Site | Nashville | Tennessee | United States | |
| 25 | Research Site | Galveston | Texas | United States | |
| 26 | Research Site | Houston | Texas | United States |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Study Director: Steven Simonson, MD, AstraZeneca
- Study Director: Wayne Dankner, MD, Parexel
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00615017
Other Study ID Numbers:
- D0620C00004
First Posted:
Feb 14, 2008
Last Update Posted:
Aug 22, 2013
Last Verified:
Jul 1, 2013
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 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 |
|---|---|
| Pre-assignment Detail | 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 |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Period Title: Overall Study | ||||||
| STARTED | 8 | 9 | 12 | 10 | 8 | 23 |
| COMPLETED | 8 | 8 | 7 | 9 | 7 | 20 |
| NOT COMPLETED | 0 | 1 | 5 | 1 | 1 | 3 |
Baseline Characteristics
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo | Total of all reporting groups |
| Overall Participants | 8 | 9 | 12 | 10 | 8 | 23 | 70 |
| Age (Year) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [Year] |
53
(11.8)
|
49.7
(15)
|
55.1
(10.8)
|
53
(17.9)
|
63.5
(16.1)
|
58.9
(17.4)
|
56.1
(15.5)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
2
25%
|
4
44.4%
|
7
58.3%
|
7
70%
|
6
75%
|
12
52.2%
|
38
54.3%
|
| Male |
6
75%
|
5
55.6%
|
5
41.7%
|
3
30%
|
2
25%
|
11
47.8%
|
32
45.7%
|
| Mechanical ventilation (Number) [Number] | |||||||
| Yes |
7
87.5%
|
8
88.9%
|
9
75%
|
8
80%
|
8
100%
|
20
87%
|
60
85.7%
|
| No |
1
12.5%
|
0
0%
|
2
16.7%
|
1
10%
|
0
0%
|
3
13%
|
7
10%
|
| Missing |
0
0%
|
1
11.1%
|
1
8.3%
|
1
10%
|
0
0%
|
0
0%
|
3
4.3%
|
| Organ failure site (Number) [Number] | |||||||
| Cardiovascular |
2
25%
|
2
22.2%
|
3
25%
|
3
30%
|
2
25%
|
7
30.4%
|
19
27.1%
|
| Pulmonary dysfunction |
2
25%
|
2
22.2%
|
3
25%
|
1
10%
|
2
25%
|
3
13%
|
13
18.6%
|
| Cardiovascular and pulmonary dysfunction |
4
50%
|
5
55.6%
|
6
50%
|
6
60%
|
4
50%
|
13
56.5%
|
38
54.3%
|
| Shock (Number) [Number] | |||||||
| Yes |
5
62.5%
|
6
66.7%
|
9
75%
|
9
90%
|
7
87.5%
|
20
87%
|
56
80%
|
| No |
3
37.5%
|
3
33.3%
|
3
25%
|
1
10%
|
1
12.5%
|
3
13%
|
14
20%
|
Outcome Measures
| Title | Change From Baseline in Creatinine Values |
|---|---|
| Description | 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). |
| Time Frame | End of study (Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 5 | 4 | 7 | 8 | 6 | 15 |
| Mean (Full Range) [μmol/L] |
-78.6
(-239)
|
-196.8
(-681)
|
-25.1
(-126)
|
-10.9
(-68)
|
159.0
(-89)
|
-57.4
(-191)
|
| Title | Change From Baseline in Alanine Aminotransferase Values |
|---|---|
| Description | 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). |
| Time Frame | End of study (Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 5 | 3 | 7 | 7 | 6 | 15 |
| Mean (Full Range) [μkat/L] |
-0.998
(-3.24)
|
0.017
(-0.25)
|
-3.133
(-20.62)
|
-0.520
(-2.05)
|
-0.825
(-4.53)
|
-0.111
(-0.79)
|
| Title | Change From Baseline in Aspartate Aminotransferase Values |
|---|---|
| Description | 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). |
| Time Frame | End of study (Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 5 | 3 | 7 | 7 | 6 | 15 |
| Mean (Full Range) [μkat/L] |
-2.298
(-5.56)
|
-0.213
(-0.43)
|
-3.647
(-21.36)
|
-0.926
(-3.27)
|
-0.998
(-3.29)
|
-0.253
(-1.54)
|
| Title | Change From Baseline in Bilirubin Values |
|---|---|
| Description | 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). |
| Time Frame | End of study (Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 5 | 3 | 7 | 7 | 6 | 15 |
| Mean (Full Range) [μmol/L] |
-11.30
(-17.1)
|
-13.10
(-34.2)
|
-10.04
(-49.6)
|
-23.71
(-71.8)
|
-2.58
(-29.1)
|
-10.00
(-37.6)
|
| Title | Change From Baseline in Haemoglobin Values |
|---|---|
| Description | 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). |
| Time Frame | End of study (Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 5 | 4 | 6 | 4 | 5 | 13 |
| Mean (Full Range) [g/L] |
7
(-18)
|
-16.3
(-42)
|
-0.8
(-31)
|
6.5
(-5)
|
-13.8
(-35)
|
-4.5
(-47)
|
| Title | Change From Baseline in White Blood Cell Values |
|---|---|
| Description | 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). |
| Time Frame | End of study (Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 5 | 4 | 6 | 4 | 5 | 13 |
| Mean (Full Range) [10^9 cells/L] |
-17.552
(-46.67)
|
-8.975
(-22.58)
|
0.413
(-8.11)
|
-0.225
(-5.60)
|
-3.482
(-13.42)
|
-9.987
(-26.40)
|
| Title | Change From Baseline in Platelet Count Values |
|---|---|
| Description | 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). |
| Time Frame | End of study (Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 5 | 3 | 5 | 4 | 4 | 13 |
| Mean (Full Range) [10^9/L] |
287
(-41)
|
117.3
(18)
|
162
(-56)
|
72.3
(-114)
|
252.5
(40)
|
145.1
(-232)
|
| Title | Change From Baseline in Prothrombin Time Values |
|---|---|
| Description | 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). |
| Time Frame | Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 5 | 4 | 6 | 7 | 5 | 17 |
| Mean (Full Range) [sec] |
-3.20
(-8.6)
|
0.53
(-0.8)
|
-1.00
(-2.4)
|
-5.31
(-14.7)
|
4.36
(-23.8)
|
1.68
(-7.5)
|
| Title | Change From Baseline in Troponin I |
|---|---|
| Description | 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). |
| Time Frame | Day 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 8 | 3 | 4 | 9 | 3 | 19 |
| Mean (Full Range) [μg/L] |
-16.454
(-127.37)
|
-9.523
(-28.58)
|
-0.630
(-1.61)
|
-1.434
(-7.21)
|
-0.027
(-0.07)
|
-0.735
(-6.77)
|
| Title | 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. |
|---|---|
| Description | 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). |
| Time Frame | Day 1 (end of infusion) for Cohorts 1 and 2; Day 5 (end of infusion) for Cohorts 3 to 5 and placebo |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 7 | 9 | 6 | 9 | 6 | 13 |
| Mean (Full Range) [msec] |
-9.9
(-37)
|
3.6
(-35)
|
-21.5
(-43)
|
-9.2
(-47)
|
21.4
(-32)
|
-3.4
(-61)
|
| Title | Change From Baseline in Calculated Mean Arterial Blood Pressure |
|---|---|
| Description | 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). |
| Time Frame | Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 3 | 6 | 4 | 6 | 5 | 11 |
| Mean (Full Range) [mmHg] |
20
(3)
|
7.3
(2)
|
5.3
(-19)
|
28.7
(4)
|
6.8
(-9)
|
18
(-4)
|
| Title | Change From Baseline in Body Weight |
|---|---|
| Description | 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). |
| Time Frame | Day 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 7 | 6 | 3 | 5 | 5 | 12 |
| Mean (Full Range) [kg] |
1.3
(-2)
|
0.2
(-7)
|
4
(1)
|
7.4
(-10)
|
0.2
(-11)
|
9.9
(0)
|
| Title | 28-Day Mortality |
|---|---|
| Description | The number of patients who had died at Day 28. Safety analysis set (ie all patients who started study drug infusion). |
| Time Frame | End of study (Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 8 | 9 | 12 | 10 | 8 | 23 |
| Number [Participants] |
2
25%
|
4
44.4%
|
5
41.7%
|
1
10%
|
1
12.5%
|
6
26.1%
|
| Title | Change From Baseline in Sequential Organ Failure Assessment (SOFA) Scores |
|---|---|
| Description | 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). |
| Time Frame | Day 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 2 | 3 | 3 | 6 | 3 | 9 |
| Mean (Full Range) [units on a scale (0 to 24)] |
-6
(-7)
|
-2
(-5)
|
-3.3
(-5)
|
-3
(-7)
|
-6
(-11)
|
-4.3
(-8)
|
| Title | 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) |
|---|---|
| Description | 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). |
| Time Frame | 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] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 7 | 8 | 0 | 0 | 0 | 0 |
| Geometric Mean (Full Range) [μg.h/mL] |
125.22
|
581.01
|
| Title | Terminal Half-life (t1/2) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2) |
|---|---|
| Description | 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). |
| Time Frame | 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] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 7 | 6 | 0 | 0 | 0 | 0 |
| Mean (Full Range) [Hours] |
17.97
(7.8)
|
19.76
(10.5)
|
| Title | Total Apparent Clearance (CL) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2) |
|---|---|
| Description | 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). |
| Time Frame | 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] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 7 | 6 | 0 | 0 | 0 | 0 |
| Mean (Full Range) [mL/min/kg] |
6.11
(1.2)
|
7.61
(0.8)
|
| Title | AUC(0-12) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) |
|---|---|
| Description | 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). |
| Time Frame | 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] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 0 | 0 | 8 | 9 | 5 | 0 |
| Geometric Mean (Full Range) [μg.h/mL] |
449.18
|
691.53
|
1872.73
|
| Title | Maximum (End of Infusion) Serum Concentration (Cinf) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3,4 and 5) |
|---|---|
| Description | 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). |
| Time Frame | 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] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 0 | 0 | 8 | 9 | 5 | 0 |
| Geometric Mean (Full Range) [μg/mL] |
107.84
|
160.09
|
351.52
|
| Title | Time to Reach Cinf (Tmax) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) |
|---|---|
| Description | 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). |
| Time Frame | 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] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 0 | 0 | 8 | 9 | 5 | 0 |
| Median (Full Range) [Hours] |
0.92
|
1.08
|
1.12
|
| Title | AUC(0-12) of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) |
|---|---|
| Description | 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). |
| Time Frame | 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 infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 0 | 0 | 6 | 7 | 4 | 0 |
| Geometric Mean (Full Range) [μg.h/mL] |
162.82
|
251.59
|
980.95
|
| Title | Cinf of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) |
|---|---|
| Description | 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). |
| Time Frame | 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 infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 0 | 0 | 6 | 7 | 4 | 0 |
| Geometric Mean (Full Range) [μg/mL] |
28.37
|
42.51
|
151.76
|
| Title | Tmax of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) |
|---|---|
| Description | 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). |
| Time Frame | 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 infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 0 | 0 | 6 | 7 | 4 | 0 |
| Median (Full Range) [Hours] |
0.54
|
1.00
|
0.74
|
| Title | Number of Patients Below Tumour Necrosis Factor (TNF)-Alpha Limit of Quantification (LOQ) at 24 Hours (n< LOQ) |
|---|---|
| Description | 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). |
| Time Frame | 24 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed relates to the number of evaluable patients at the specified time point. |
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo |
| Measure Participants | 7 | 9 | 10 | 9 | 5 | 22 |
| Number [Participants] |
1.0
12.5%
|
3.0
33.3%
|
5.0
41.7%
|
6.0
60%
|
4.0
50%
|
0.0
0%
|
Adverse Events
| Time Frame | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||
| Arm/Group Title | AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo | ||||||
| Arm/Group Description | AZD9773: single infusion of 50 units/kg | AZD9773: single infusion of 250 units/kg | AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs | AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs | AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs | Placebo | ||||||
All Cause Mortality |
||||||||||||
| AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||
Serious Adverse Events |
||||||||||||
| AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/8 (37.5%) | 6/9 (66.7%) | 7/12 (58.3%) | 3/10 (30%) | 4/8 (50%) | 13/23 (56.5%) | ||||||
| Cardiac disorders | ||||||||||||
| Cardiac Arrest | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 2/23 (8.7%) | 2 |
| Acute Myocardial Infarction | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 1/23 (4.3%) | 1 |
| Cardiac Failure | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/23 (0%) | 0 |
| Supraventricular Tachycardia | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 2/23 (8.7%) | 2 |
| Atrial Fibrillation | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 4/23 (17.4%) | 4 |
| Gastrointestinal disorders | ||||||||||||
| Enterocutaneous Fistula | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 | 0/23 (0%) | 0 |
| Intestinal Ischaemia | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 | 1/23 (4.3%) | 1 |
| Intestinal Perforation | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 1/23 (4.3%) | 1 |
| Infections and infestations | ||||||||||||
| Sepsis | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 3/12 (25%) | 3 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 1/23 (4.3%) | 1 |
| Pneumonia | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 3/23 (13%) | 3 |
| Septic Shock | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 | 2/23 (8.7%) | 2 |
| Empyema | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/23 (0%) | 0 |
| Endocarditis | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/23 (0%) | 0 |
| Cellulitis | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 | 1/23 (4.3%) | 2 |
| Injury, poisoning and procedural complications | ||||||||||||
| Medical Device Complication | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/23 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| Acidosis | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 1/23 (4.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Muscle Haemorrhage | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 1/23 (4.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Lung Neoplasm Malignant | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/23 (0%) | 0 |
| Nervous system disorders | ||||||||||||
| Cerebral Infarction | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/23 (0%) | 0 |
| Haemorrhage Intracranial | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 1/23 (4.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Pulmonary Embolism | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 | 1/23 (4.3%) | 1 |
| Respiratory Failure | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 2/10 (20%) | 2 | 0/8 (0%) | 0 | 3/23 (13%) | 3 |
| Pneumonia Aspiration | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 0/23 (0%) | 0 |
| Hypoxia | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 2/23 (8.7%) | 2 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| Toxic Epidermal Necrolysis | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/23 (0%) | 0 |
| Vascular disorders | ||||||||||||
| Deep Vein Thrombosis | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 2 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 1/23 (4.3%) | 1 |
| Shock | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/23 (0%) | 0 |
| Shock Haemorrhagic | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 1/23 (4.3%) | 1 |
| Peripheral Ischaemia | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/12 (16.7%) | 2 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 1/23 (4.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||
| AZD9773 Cohort 1 (50 Units/kg) | AZD9773 Cohort 2 (250 Units/kg) | AZD9773 Cohort 3 (250/50 Units/kg) | AZD9773 Cohort 4 (500/100 Units/kg) | AZD9773 Cohort 5 (750/250 Units/kg) | Placebo | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/8 (100%) | 8/9 (88.9%) | 11/12 (91.7%) | 7/10 (70%) | 7/8 (87.5%) | 22/23 (95.7%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 1/8 (12.5%) | 1 | 3/9 (33.3%) | 3 | 2/12 (16.7%) | 2 | 1/10 (10%) | 1 | 2/8 (25%) | 3 | 4/23 (17.4%) | 4 |
| Hypercoagulation | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 | 0/23 (0%) | 0 |
| Leucocytosis | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 1/8 (12.5%) | 1 | 2/23 (8.7%) | 2 |
| Thrombocytopenia | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 2/12 (16.7%) | 2 | 1/10 (10%) | 1 | 1/8 (12.5%) | 1 | 2/23 (8.7%) | 2 |
| Coagulopathy | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/12 (16.7%) | 2 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 1/23 (4.3%) | 1 |
| Heparin-Induced Thrombocytopenia | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 1/23 (4.3%) | 1 |
| Thrombocythaemia | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 3/23 (13%) | 3 |
| Cardiac disorders | ||||||||||||
| Atrial Flutter | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 1/23 (4.3%) | ||||||
| Arrhythmia | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Bradycardia | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 2/10 (20%) | 0/8 (0%) | 3/23 (13%) | ||||||
| Bundle Branch Block Right | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Supraventricular Tachycardia | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Tachycardia | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Ventricular Tachycardia | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Endocrine disorders | ||||||||||||
| Adrenal Insufficiency | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Hypothyroidism | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Eye disorders | ||||||||||||
| Conjunctivitis | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Scleral Haemorrhage | 2/8 (25%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Scleral Oedema | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Abdominal Compartment Syndrome | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Cheilitis | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Diarrhoea | 2/8 (25%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 1/8 (12.5%) | 4/23 (17.4%) | ||||||
| Gastric Ulcer | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 1/23 (4.3%) | ||||||
| Nausea | 1/8 (12.5%) | 1/9 (11.1%) | 1/12 (8.3%) | 1/10 (10%) | 1/8 (12.5%) | 3/23 (13%) | ||||||
| Abdominal Pain | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Constipation | 2/8 (25%) | 2/9 (22.2%) | 2/12 (16.7%) | 1/10 (10%) | 0/8 (0%) | 6/23 (26.1%) | ||||||
| Dyspepsia | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Dysphagia | 1/8 (12.5%) | 0/9 (0%) | 1/12 (8.3%) | 1/10 (10%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Flatulence | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Gastrointestinal Motility Disorder | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Ileus | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Intestinal Ischaemia | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 1/23 (4.3%) | ||||||
| Rectal Haemorrhage | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Salivary Hypersecretion | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Vomiting | 2/8 (25%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| General disorders | ||||||||||||
| General Oedema | 0/8 (0%) | 1/9 (11.1%) | 3/12 (25%) | 2/10 (20%) | 3/8 (37.5%) | 3/23 (13%) | ||||||
| Asthenia | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 1/8 (12.5%) | 1/23 (4.3%) | ||||||
| Hypothermia | 0/8 (0%) | 0/9 (0%) | 2/12 (16.7%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Oedema Periheral | 2/8 (25%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 4/23 (17.4%) | ||||||
| Chest Pain | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Chills | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Face Oedema | 0/8 (0%) | 0/9 (0%) | 2/12 (16.7%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Multi-Organ Failure | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Pain | 1/8 (12.5%) | 0/9 (0%) | 1/12 (8.3%) | 1/10 (10%) | 0/8 (0%) | 4/23 (17.4%) | ||||||
| Pyrexia | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Hepatobiliary disorders | ||||||||||||
| Hyperbilirubinaemia | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 1/23 (4.3%) | ||||||
| Ischaemic Hepatitis | 1/8 (12.5%) | 0/9 (0%) | 1/12 (8.3%) | 1/10 (10%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Cholelithiasis | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Jaundice | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Infections and infestations | ||||||||||||
| Enterobacter Pneumonia | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Infected Skin Ulcer | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Pelvic Abscess | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Sinusitis | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Systemic Candida | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Tracheobronchitis | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Urinary Tract Infection Enterococcal | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Bacteraemia | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Candiduria | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Central Line Infection | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Clostridial Infection | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Clostridium Difficile Colitis | 0/8 (0%) | 1/9 (11.1%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Escherichia Urinary Tract Infection | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Fungal Skin Infection | 1/8 (12.5%) | 1/9 (11.1%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Gangrene | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Herpes Simplex | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Lung Infection Pseudomonal | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Oral Herpes | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Pneumonia Bacterial | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 1/10 (10%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Pneumonia Escherichia | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Pneumonia Staphylococcal | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Urinary Tract Infection | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Vulvovaginal Mycotic Infection | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Injury, poisoning and procedural complications | ||||||||||||
| Bloody Airway Discharge | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Procedural Hypotension | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Contusion | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Endotracheal Intubation Complication | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Excoriation | 1/8 (12.5%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Fall | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Gastrointestinal Stoma Complication | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Skin Laceration | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Investigations | ||||||||||||
| Airway Peak Pressure Increased | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Blood Albumin Decreased | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Blood Alkaline Phosphatase Decreased | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Blood Phosphorus Decreased | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Blood Sodium Decreased | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Aspartate Aminotransferase Increased | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Blood Creatine Phosphokinase Increased | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Blood Lactate Dehydrogenase Increased | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Brain Natriuretic Peptide Increased | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Breath Sounds Abnormal | 0/8 (0%) | 1/9 (11.1%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Clostridium Difficile Toxin Test Positive | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Ejection Fraction Decreased | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Fibrin D Dimer Increased | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Haemoglobin Decreased | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Hepatic Enzyme Increased | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Oxygen Saturation Decreased | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Troponin Increased | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Urinary Sediment Present | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Urine Output Decreased | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Metabolism and nutrition disorders | ||||||||||||
| Hypoglycaemia | 1/8 (12.5%) | 1/9 (11.1%) | 1/12 (8.3%) | 4/10 (40%) | 3/8 (37.5%) | 2/23 (8.7%) | ||||||
| Hypernatraemia | 1/8 (12.5%) | 1/9 (11.1%) | 0/12 (0%) | 3/10 (30%) | 2/8 (25%) | 2/23 (8.7%) | ||||||
| Hypercalcaemia | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Hyperglycaemia | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 2/23 (8.7%) | ||||||
| Hypermagnesaemia | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Hypophosphataemia | 2/8 (25%) | 1/9 (11.1%) | 0/12 (0%) | 2/10 (20%) | 1/8 (12.5%) | 2/23 (8.7%) | ||||||
| Feeding Disorder | 1/8 (12.5%) | 2/9 (22.2%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Fluid Overload | 0/8 (0%) | 2/9 (22.2%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Hyperkalaemia | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Hypokalaemia | 2/8 (25%) | 1/9 (11.1%) | 0/12 (0%) | 2/10 (20%) | 0/8 (0%) | 7/23 (30.4%) | ||||||
| Hypomagnesaemia | 0/8 (0%) | 1/9 (11.1%) | 2/12 (16.7%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Hyponatraemia | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Lactic Acidosis | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Malnutrition | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Metabolic Acidosis | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Musculoskeletal Pain | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Pain In Extremity | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Nervous system disorders | ||||||||||||
| Aphasia | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Convulsion | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Depressed Level Of Consciousness | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Headache | 1/8 (12.5%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Unresponsive To Stimuli | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Psychiatric disorders | ||||||||||||
| Agitation | 2/8 (25%) | 2/9 (22.2%) | 1/12 (8.3%) | 3/10 (30%) | 1/8 (12.5%) | 4/23 (17.4%) | ||||||
| Anxiety | 1/8 (12.5%) | 0/9 (0%) | 2/12 (16.7%) | 0/10 (0%) | 1/8 (12.5%) | 2/23 (8.7%) | ||||||
| Confusional State | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Depression | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Disorientation | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Hallucination | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Insomnia | 1/8 (12.5%) | 2/9 (22.2%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Mental Status Changes | 1/8 (12.5%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Renal and urinary disorders | ||||||||||||
| Renal Failure Acute | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Renal Failure | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Renal Impairment | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Reproductive system and breast disorders | ||||||||||||
| Menorrhagia | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Scrotal Oedema | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 2/23 (8.7%) | ||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Aspiration | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Atelectasis | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Dyspnoea | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Hiccups | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Lung Disorder | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Nasal Congestion | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Oropharyngeal Pain | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Pleural Effusion | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 3/23 (13%) | ||||||
| Pulmonary Congestion | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Pulmonary Oedema | 1/8 (12.5%) | 1/9 (11.1%) | 1/12 (8.3%) | 1/10 (10%) | 0/8 (0%) | 3/23 (13%) | ||||||
| Respiratory Alkalosis | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Respiratory Distress | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Rhonchi | 1/8 (12.5%) | 1/9 (11.1%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Wheezing | 1/8 (12.5%) | 2/9 (22.2%) | 0/12 (0%) | 1/10 (10%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Skin and subcutaneous tissue disorders | ||||||||||||
| Decubitus Ulcer | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 2/10 (20%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Drug Eruption | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Erythema | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 1/8 (12.5%) | 6/23 (26.1%) | ||||||
| Rash | 1/8 (12.5%) | 0/9 (0%) | 1/12 (8.3%) | 1/10 (10%) | 1/8 (12.5%) | 2/23 (8.7%) | ||||||
| Rash Maculo-Papular | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Skin Discolouration | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Skin Disorder | 0/8 (0%) | 1/9 (11.1%) | 1/12 (8.3%) | 1/10 (10%) | 1/8 (12.5%) | 2/23 (8.7%) | ||||||
| Blister | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 1/23 (4.3%) | ||||||
| Periorbital Oedema | 1/8 (12.5%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Petechiae | 0/8 (0%) | 0/9 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/8 (0%) | 0/23 (0%) | ||||||
| Vascular disorders | ||||||||||||
| Hypertension | 0/8 (0%) | 1/9 (11.1%) | 0/12 (0%) | 2/10 (20%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
| Hypotension | 0/8 (0%) | 1/9 (11.1%) | 2/12 (16.7%) | 1/10 (10%) | 1/8 (12.5%) | 2/23 (8.7%) | ||||||
| Peripheral Coldness | 0/8 (0%) | 0/9 (0%) | 0/12 (0%) | 0/10 (0%) | 1/8 (12.5%) | 0/23 (0%) | ||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Justin Lindemann |
|---|---|
| Organization | AstraZeneca |
| Phone | |
| ClinicalTrialTransparency@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00615017
Other Study ID Numbers:
- D0620C00004
First Posted:
Feb 14, 2008
Last Update Posted:
Aug 22, 2013
Last Verified:
Jul 1, 2013