Trial Outcomes & Findings for Dose Escalation, Combination Chemotherapy Safety Study of Birinapant (TL32711), in Subjects With Advanced or Metastatic Solid Tumors (NCT NCT01188499)
NCT ID: NCT01188499
Last Updated: 2016-05-30
Results Overview
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
176 participants
Primary outcome timeframe
1 Cycle (3-4 weeks)
Results posted on
2016-05-30
Participant Flow
Participant milestones
| Measure |
Arm 1: Carboplatin/Paclitaxel + Birinapant
Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 2: Irinotecan + Birinapant
Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 3: Docetaxel + Birinapant
Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 4: Gemcitabine + Birinapant
Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
|
Arm 5: Liposomal Doxorubicin + Birinapant
Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
24
|
83
|
33
|
18
|
18
|
|
Overall Study
COMPLETED
|
24
|
83
|
33
|
18
|
18
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Dose Escalation, Combination Chemotherapy Safety Study of Birinapant (TL32711), in Subjects With Advanced or Metastatic Solid Tumors
Baseline characteristics by cohort
| Measure |
Arm 1: Carboplatin/Paclitaxel + Birinapant
n=24 Participants
Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 2: Irinotecan + Birinapant
n=83 Participants
Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 3: Docetaxel + Birinapant
n=33 Participants
Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 4: Gemcitabine + Birinapant
n=18 Participants
Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
|
Arm 5: Liposomal Doxorubicin + Birinapant
n=18 Participants
Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
|
Total
n=176 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
63 years
STANDARD_DEVIATION 8.77 • n=5 Participants
|
59.6 years
STANDARD_DEVIATION 11.58 • n=7 Participants
|
60.7 years
STANDARD_DEVIATION 11.16 • n=5 Participants
|
56.7 years
STANDARD_DEVIATION 8.55 • n=4 Participants
|
56.5 years
STANDARD_DEVIATION 10.44 • n=21 Participants
|
59.7 years
STANDARD_DEVIATION 10.82 • n=8 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
91 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
85 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
8 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=5 Participants
|
81 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
168 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
23 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=5 Participants
|
71 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
151 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
83 participants
n=7 Participants
|
33 participants
n=5 Participants
|
18 participants
n=4 Participants
|
18 participants
n=21 Participants
|
176 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 1 Cycle (3-4 weeks)Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
Outcome measures
| Measure |
Arm 1: Carboplatin/Paclitaxel + TL32711
n=24 Participants
Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 2: Irinotecan + TL32711
n=83 Participants
Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 3: Docetaxel + TL32711
n=33 Participants
Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 4: Gemcitabine + TL32711
n=18 Participants
Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
|
Arm 5: Liposomal Doxorubicin
n=18 Participants
Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
|
|---|---|---|---|---|---|
|
Number of Subjects With Adverse Events as a Measure of Safety and Tolerability
|
24 participants
|
83 participants
|
33 participants
|
18 participants
|
18 participants
|
SECONDARY outcome
Timeframe: Every 2 cyclesPopulation: Intent-to-treat (ITT)
Tumor burden according to Response Evaluation Criteria in Solid Tumors (RECIST) and time to progression
Outcome measures
| Measure |
Arm 1: Carboplatin/Paclitaxel + TL32711
n=24 Participants
Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 2: Irinotecan + TL32711
n=83 Participants
Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 3: Docetaxel + TL32711
n=33 Participants
Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 4: Gemcitabine + TL32711
n=18 Participants
Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
|
Arm 5: Liposomal Doxorubicin
n=18 Participants
Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
|
|---|---|---|---|---|---|
|
Evaluation of Anti-tumor Efficacy
|
5 participants
|
8 participants
|
3 participants
|
2 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Cycle 1 and Cycle 2Measurement of TL32711 pharmacokinetics: Maximum plasma concentration (Cmax), area under the curve (AUC), half-life (t1/2) and assessment of translational biomarkers in plasma, PBMC's and tumor biopsies. Gene expression profiling of tumor tissue.
Outcome measures
Outcome data not reported
Adverse Events
Arm 1: Carboplatin/Paclitaxel + Birinapant
Serious events: 9 serious events
Other events: 24 other events
Deaths: 0 deaths
Arm 2: Irinotecan + Birinapant
Serious events: 41 serious events
Other events: 83 other events
Deaths: 0 deaths
Arm 3: Docetaxel + Birinapant
Serious events: 16 serious events
Other events: 33 other events
Deaths: 0 deaths
Arm 4: Gemcitabine + Birinapant
Serious events: 13 serious events
Other events: 18 other events
Deaths: 0 deaths
Arm 5: Liposomal Doxorubicin + Birinapant
Serious events: 9 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm 1: Carboplatin/Paclitaxel + Birinapant
n=24 participants at risk
Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 2: Irinotecan + Birinapant
n=83 participants at risk
Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 3: Docetaxel + Birinapant
n=33 participants at risk
Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 4: Gemcitabine + Birinapant
n=18 participants at risk
Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
|
Arm 5: Liposomal Doxorubicin + Birinapant
n=18 participants at risk
Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
|
|---|---|---|---|---|---|
|
Infections and infestations
Kidney infection
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
11.1%
2/18
|
0.00%
0/18
|
|
Infections and infestations
Pneumonia
|
12.5%
3/24
|
2.4%
2/83
|
15.2%
5/33
|
11.1%
2/18
|
5.6%
1/18
|
|
Blood and lymphatic system disorders
Anaemia
|
8.3%
2/24
|
3.6%
3/83
|
6.1%
2/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/24
|
8.4%
7/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/24
|
6.0%
5/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Leukocytosis
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/24
|
3.6%
3/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Cardiac disorders
Cardiac tamponade
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Cardiac disorders
Stress cardiomyopathy
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Congenital, familial and genetic disorders
Pyloric stenosis
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/24
|
4.8%
4/83
|
3.0%
1/33
|
0.00%
0/18
|
11.1%
2/18
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.2%
1/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Anal fissure
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/24
|
3.6%
3/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Constipation
|
8.3%
2/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/24
|
7.2%
6/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/24
|
2.4%
2/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Nausea
|
4.2%
1/24
|
2.4%
2/83
|
0.00%
0/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Reflux gastritis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
4.2%
1/24
|
3.6%
3/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Vomiting
|
4.2%
1/24
|
6.0%
5/83
|
0.00%
0/33
|
11.1%
2/18
|
11.1%
2/18
|
|
General disorders
Chest pain
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
General disorders
Death
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
General disorders
Disease progression
|
0.00%
0/24
|
4.8%
4/83
|
15.2%
5/33
|
5.6%
1/18
|
5.6%
1/18
|
|
General disorders
Generalized oedema
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
General disorders
Oedema peripheral
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
General disorders
Pain
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
General disorders
Pyrexia
|
0.00%
0/24
|
1.2%
1/83
|
6.1%
2/33
|
16.7%
3/18
|
5.6%
1/18
|
|
Hepatobiliary disorders
Bile duct stenosis
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Bronchitis
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Infections and infestations
Cholangitis suppurative
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Infections and infestations
Cystitis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Device related infection
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Empyema
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Escherichia bacteraemia
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Infections and infestations
Sepsis
|
4.2%
1/24
|
4.8%
4/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Infections and infestations
Septic shock
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/24
|
6.0%
5/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Injury, poisoning and procedural complications
Fall
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Investigations
International normalised ratio increased
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Dehydration
|
4.2%
1/24
|
9.6%
8/83
|
3.0%
1/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/24
|
0.00%
0/83
|
6.1%
2/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
11.1%
2/18
|
0.00%
0/18
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial tumour haemorrhage
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Nervous system disorders
Spinal cord compression
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Psychiatric disorders
Confusional state
|
4.2%
1/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/24
|
4.8%
4/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/24
|
2.4%
2/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial fistula
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
16.7%
3/18
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/24
|
4.8%
4/83
|
3.0%
1/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/24
|
1.2%
1/83
|
3.0%
1/33
|
5.6%
1/18
|
11.1%
2/18
|
|
Vascular disorders
Venous thrombosis limb
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/24
|
3.6%
3/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Caecitis
|
0.00%
0/24
|
2.4%
2/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
General disorders
Asthenia
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
General disorders
Fatigue
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Infections and infestations
Bacterial sepsis
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer stage IV
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Vascular disorders
Hypotension
|
0.00%
0/24
|
6.0%
5/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
Other adverse events
| Measure |
Arm 1: Carboplatin/Paclitaxel + Birinapant
n=24 participants at risk
Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 2: Irinotecan + Birinapant
n=83 participants at risk
Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 3: Docetaxel + Birinapant
n=33 participants at risk
Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
|
Arm 4: Gemcitabine + Birinapant
n=18 participants at risk
Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
|
Arm 5: Liposomal Doxorubicin + Birinapant
n=18 participants at risk
Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle).
TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
|
|---|---|---|---|---|---|
|
Ear and labyrinth disorders
External ear pain
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
6/24
|
69.9%
58/83
|
36.4%
12/33
|
27.8%
5/18
|
16.7%
3/18
|
|
Ear and labyrinth disorders
Hearing impaired
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Dry mouth
|
4.2%
1/24
|
8.4%
7/83
|
12.1%
4/33
|
11.1%
2/18
|
5.6%
1/18
|
|
Endocrine disorders
Cushingoid
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Eye disorders
Arcus lipoides
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Eye disorders
Eye irritation
|
4.2%
1/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Eye disorders
Lacrimation increased
|
12.5%
3/24
|
1.2%
1/83
|
12.1%
4/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Dyspepsia
|
8.3%
2/24
|
7.2%
6/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/24
|
2.4%
2/83
|
9.1%
3/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/24
|
6.0%
5/83
|
3.0%
1/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
12.5%
3/24
|
2.4%
2/83
|
3.0%
1/33
|
11.1%
2/18
|
11.1%
2/18
|
|
Gastrointestinal disorders
Gingival pain
|
4.2%
1/24
|
2.4%
2/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Eye disorders
Vision blurred
|
4.2%
1/24
|
2.4%
2/83
|
6.1%
2/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Abdominal discomfort
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
11.1%
2/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Abdominal distension
|
8.3%
2/24
|
3.6%
3/83
|
12.1%
4/33
|
33.3%
6/18
|
11.1%
2/18
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
4/24
|
38.6%
32/83
|
15.2%
5/33
|
27.8%
5/18
|
22.2%
4/18
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/24
|
2.4%
2/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Abdominal pain upper
|
16.7%
4/24
|
10.8%
9/83
|
15.2%
5/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Abdominal tenderness
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Ascites
|
8.3%
2/24
|
8.4%
7/83
|
12.1%
4/33
|
11.1%
2/18
|
16.7%
3/18
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Constipation
|
41.7%
10/24
|
30.1%
25/83
|
45.5%
15/33
|
27.8%
5/18
|
50.0%
9/18
|
|
Blood and lymphatic system disorders
Anaemia
|
66.7%
16/24
|
42.2%
35/83
|
39.4%
13/33
|
61.1%
11/18
|
22.2%
4/18
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/24
|
1.2%
1/83
|
3.0%
1/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/24
|
8.4%
7/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
16.7%
3/18
|
5.6%
1/18
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/24
|
9.6%
8/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
8.3%
2/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Neutropenia
|
29.2%
7/24
|
27.7%
23/83
|
30.3%
10/33
|
38.9%
7/18
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
45.8%
11/24
|
33.7%
28/83
|
21.2%
7/33
|
44.4%
8/18
|
11.1%
2/18
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/24
|
1.2%
1/83
|
3.0%
1/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Cardiac disorders
Cardiac tamponade
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Cardiac disorders
Palpitations
|
4.2%
1/24
|
1.2%
1/83
|
0.00%
0/33
|
11.1%
2/18
|
5.6%
1/18
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Cardiac disorders
Stress cardiomyopathy
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Cardiac disorders
Tachycardia
|
20.8%
5/24
|
7.2%
6/83
|
12.1%
4/33
|
16.7%
3/18
|
11.1%
2/18
|
|
Cardiac disorders
Ventricular extrasystoles
|
8.3%
2/24
|
2.4%
2/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Haemorrhoids
|
4.2%
1/24
|
1.2%
1/83
|
3.0%
1/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Mucous stools
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Nausea
|
58.3%
14/24
|
74.7%
62/83
|
48.5%
16/33
|
50.0%
9/18
|
61.1%
11/18
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Oral pain
|
4.2%
1/24
|
4.8%
4/83
|
9.1%
3/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
8.3%
2/24
|
1.2%
1/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Reflux gastritis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Stomatitis
|
12.5%
3/24
|
13.3%
11/83
|
15.2%
5/33
|
22.2%
4/18
|
11.1%
2/18
|
|
Gastrointestinal disorders
Tongue ulceration
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
8/24
|
56.6%
47/83
|
27.3%
9/33
|
55.6%
10/18
|
38.9%
7/18
|
|
General disorders
Asthenia
|
37.5%
9/24
|
27.7%
23/83
|
30.3%
10/33
|
38.9%
7/18
|
27.8%
5/18
|
|
General disorders
Catheter site reaction
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
General disorders
Chest discomfort
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
General disorders
Chest pain
|
4.2%
1/24
|
3.6%
3/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
General disorders
Chills
|
25.0%
6/24
|
16.9%
14/83
|
12.1%
4/33
|
11.1%
2/18
|
11.1%
2/18
|
|
General disorders
Device occlusion
|
4.2%
1/24
|
6.0%
5/83
|
6.1%
2/33
|
5.6%
1/18
|
0.00%
0/18
|
|
General disorders
Disease progression
|
0.00%
0/24
|
4.8%
4/83
|
15.2%
5/33
|
5.6%
1/18
|
5.6%
1/18
|
|
General disorders
Early satiety
|
0.00%
0/24
|
3.6%
3/83
|
6.1%
2/33
|
5.6%
1/18
|
5.6%
1/18
|
|
General disorders
Face oedema
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
General disorders
Fatigue
|
70.8%
17/24
|
68.7%
57/83
|
63.6%
21/33
|
72.2%
13/18
|
72.2%
13/18
|
|
General disorders
Generalized oedema
|
0.00%
0/24
|
2.4%
2/83
|
3.0%
1/33
|
5.6%
1/18
|
0.00%
0/18
|
|
General disorders
Influenza like illness
|
4.2%
1/24
|
1.2%
1/83
|
3.0%
1/33
|
5.6%
1/18
|
0.00%
0/18
|
|
General disorders
Infusion related reaction
|
12.5%
3/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
General disorders
Infusion site reaction
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
General disorders
Localised oedema
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
General disorders
Malaise
|
4.2%
1/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
5.6%
1/18
|
|
General disorders
Mucosal inflammation
|
0.00%
0/24
|
2.4%
2/83
|
30.3%
10/33
|
11.1%
2/18
|
5.6%
1/18
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/24
|
2.4%
2/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
General disorders
Oedema peripheral
|
37.5%
9/24
|
33.7%
28/83
|
45.5%
15/33
|
50.0%
9/18
|
50.0%
9/18
|
|
General disorders
Pain
|
8.3%
2/24
|
3.6%
3/83
|
6.1%
2/33
|
5.6%
1/18
|
0.00%
0/18
|
|
General disorders
Pyrexia
|
25.0%
6/24
|
19.3%
16/83
|
18.2%
6/33
|
44.4%
8/18
|
22.2%
4/18
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/24
|
1.2%
1/83
|
6.1%
2/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Immune system disorders
Drug hypersensitivity
|
12.5%
3/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Bronchitis
|
8.3%
2/24
|
0.00%
0/83
|
3.0%
1/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Candidiasis
|
0.00%
0/24
|
7.2%
6/83
|
15.2%
5/33
|
0.00%
0/18
|
11.1%
2/18
|
|
Infections and infestations
Cellulitis
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Cystitis
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Device related infection
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Empyema
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Folliculitis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Infections and infestations
Fungal infection
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Fungal skin infection
|
0.00%
0/24
|
2.4%
2/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Infections and infestations
Herpes zoster
|
8.3%
2/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Infections and infestations
Kidney infection
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/24
|
2.4%
2/83
|
3.0%
1/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Pneumonia
|
16.7%
4/24
|
3.6%
3/83
|
9.1%
3/33
|
5.6%
1/18
|
11.1%
2/18
|
|
Infections and infestations
Rhinitis
|
8.3%
2/24
|
7.2%
6/83
|
9.1%
3/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Sepsis
|
4.2%
1/24
|
4.8%
4/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Infections and infestations
Septic shock
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Infections and infestations
Sinusitis
|
8.3%
2/24
|
1.2%
1/83
|
6.1%
2/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Infections and infestations
Upper respiratory tract infection
|
12.5%
3/24
|
6.0%
5/83
|
9.1%
3/33
|
5.6%
1/18
|
11.1%
2/18
|
|
Infections and infestations
Urinary tract infection
|
12.5%
3/24
|
14.5%
12/83
|
9.1%
3/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Urosepsis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Vaginal infection
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Infections and infestations
Vulvovaginal candidiasis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Injury, poisoning and procedural complications
Contusion
|
8.3%
2/24
|
6.0%
5/83
|
3.0%
1/33
|
16.7%
3/18
|
0.00%
0/18
|
|
Injury, poisoning and procedural complications
Excoriation
|
8.3%
2/24
|
3.6%
3/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Injury, poisoning and procedural complications
Fall
|
12.5%
3/24
|
2.4%
2/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Injury, poisoning and procedural complications
Feeding tube complication
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Injury, poisoning and procedural complications
Post procedural oedema
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Investigations
Activated partial thromboplastin time prolonged
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Investigations
Alanine aminotransferase increased
|
4.2%
1/24
|
4.8%
4/83
|
6.1%
2/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Investigations
Aspartate aminotransferase increased
|
4.2%
1/24
|
7.2%
6/83
|
6.1%
2/33
|
11.1%
2/18
|
0.00%
0/18
|
|
Investigations
Bacterial test positive
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Investigations
Blood alkaline phosphatase increased
|
4.2%
1/24
|
7.2%
6/83
|
3.0%
1/33
|
16.7%
3/18
|
5.6%
1/18
|
|
Investigations
Blood bilirubin increased
|
4.2%
1/24
|
9.6%
8/83
|
0.00%
0/33
|
16.7%
3/18
|
11.1%
2/18
|
|
Investigations
Blood creatinine increased
|
12.5%
3/24
|
13.3%
11/83
|
9.1%
3/33
|
16.7%
3/18
|
0.00%
0/18
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/24
|
8.4%
7/83
|
15.2%
5/33
|
11.1%
2/18
|
16.7%
3/18
|
|
Investigations
Blood urea increased
|
12.5%
3/24
|
6.0%
5/83
|
9.1%
3/33
|
11.1%
2/18
|
5.6%
1/18
|
|
Investigations
Blood uric acid increased
|
0.00%
0/24
|
3.6%
3/83
|
6.1%
2/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Investigations
Brain natriuretic peptide increased
|
0.00%
0/24
|
0.00%
0/83
|
6.1%
2/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Investigations
Breath sounds abnormal
|
8.3%
2/24
|
4.8%
4/83
|
18.2%
6/33
|
11.1%
2/18
|
5.6%
1/18
|
|
Investigations
Ejection fraction decreased
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/24
|
9.6%
8/83
|
12.1%
4/33
|
11.1%
2/18
|
5.6%
1/18
|
|
Investigations
Haptoglobin increased
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Investigations
Heart rate irregular
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Investigations
International normalised ratio increased
|
4.2%
1/24
|
8.4%
7/83
|
6.1%
2/33
|
11.1%
2/18
|
5.6%
1/18
|
|
Investigations
Neutrophil count decreased
|
4.2%
1/24
|
7.2%
6/83
|
3.0%
1/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Investigations
Occult blood positive
|
4.2%
1/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Investigations
Platelet count decreased
|
16.7%
4/24
|
4.8%
4/83
|
0.00%
0/33
|
11.1%
2/18
|
0.00%
0/18
|
|
Investigations
Pulmonary percussion test abnormality
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Investigations
Urine analysis abnormal
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Investigations
Urine bilirubin increased
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Investigations
Urine ketone body present
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Investigations
Urine leukocyte esterase positive
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Investigations
Urine output decreased
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Investigations
Urine output increased
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Investigations
Urobilinogen urine increased
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Investigations
Vitamin D decreased
|
0.00%
0/24
|
0.00%
0/83
|
6.1%
2/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Investigations
Weight decreased
|
16.7%
4/24
|
19.3%
16/83
|
9.1%
3/33
|
22.2%
4/18
|
16.7%
3/18
|
|
Investigations
Weight increased
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Investigations
White blood cell count decreased
|
8.3%
2/24
|
12.0%
10/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Investigations
White blood cell count increased
|
12.5%
3/24
|
3.6%
3/83
|
6.1%
2/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Investigations
White blood cells urine positive
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Cachexia
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Decreased appetite
|
41.7%
10/24
|
50.6%
42/83
|
45.5%
15/33
|
44.4%
8/18
|
38.9%
7/18
|
|
Metabolism and nutrition disorders
Dehydration
|
16.7%
4/24
|
37.3%
31/83
|
18.2%
6/33
|
16.7%
3/18
|
27.8%
5/18
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Fluid retention
|
0.00%
0/24
|
0.00%
0/83
|
12.1%
4/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
4.2%
1/24
|
7.2%
6/83
|
6.1%
2/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
11.1%
2/18
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/24
|
7.2%
6/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
4.2%
1/24
|
10.8%
9/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/24
|
8.4%
7/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
25.0%
6/24
|
24.1%
20/83
|
24.2%
8/33
|
38.9%
7/18
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
8.3%
2/24
|
7.2%
6/83
|
6.1%
2/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
12.5%
3/24
|
14.5%
12/83
|
18.2%
6/33
|
5.6%
1/18
|
16.7%
3/18
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
4.2%
1/24
|
6.0%
5/83
|
9.1%
3/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
29.2%
7/24
|
12.0%
10/83
|
21.2%
7/33
|
22.2%
4/18
|
5.6%
1/18
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
29.2%
7/24
|
13.3%
11/83
|
15.2%
5/33
|
16.7%
3/18
|
16.7%
3/18
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
20.8%
5/24
|
3.6%
3/83
|
9.1%
3/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
8.3%
2/24
|
2.4%
2/83
|
9.1%
3/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
12.5%
3/24
|
7.2%
6/83
|
9.1%
3/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/24
|
6.0%
5/83
|
6.1%
2/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
12.5%
3/24
|
9.6%
8/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
33.3%
8/24
|
9.6%
8/83
|
15.2%
5/33
|
33.3%
6/18
|
11.1%
2/18
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
20.8%
5/24
|
1.2%
1/83
|
12.1%
4/33
|
16.7%
3/18
|
5.6%
1/18
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/24
|
1.2%
1/83
|
6.1%
2/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Nervous system disorders
Balance disorder
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Nervous system disorders
Cognitive disorder
|
8.3%
2/24
|
3.6%
3/83
|
0.00%
0/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Nervous system disorders
Dizziness
|
45.8%
11/24
|
20.5%
17/83
|
6.1%
2/33
|
11.1%
2/18
|
11.1%
2/18
|
|
Nervous system disorders
Dysgeusia
|
4.2%
1/24
|
7.2%
6/83
|
18.2%
6/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Nervous system disorders
Extensor plantar response
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Nervous system disorders
Headache
|
12.5%
3/24
|
16.9%
14/83
|
3.0%
1/33
|
27.8%
5/18
|
16.7%
3/18
|
|
Nervous system disorders
Hyporeflexia
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Nervous system disorders
Lethargy
|
4.2%
1/24
|
3.6%
3/83
|
3.0%
1/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Nervous system disorders
Nerve compression
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/24
|
3.6%
3/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Nervous system disorders
Neuropathy peripheral
|
29.2%
7/24
|
1.2%
1/83
|
21.2%
7/33
|
11.1%
2/18
|
5.6%
1/18
|
|
Nervous system disorders
Peripheral motor neuropathy
|
12.5%
3/24
|
10.8%
9/83
|
3.0%
1/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
16.7%
4/24
|
2.4%
2/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Nervous system disorders
Peroneal nerve palsy
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Nervous system disorders
Restless leg syndrome
|
8.3%
2/24
|
1.2%
1/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Nervous system disorders
Sciatica
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Nervous system disorders
Sinus headache
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Nervous system disorders
Tardive dyskinesia
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Nervous system disorders
Tremor
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Nervous system disorders
VIIth nerve paralysis
|
0.00%
0/24
|
6.0%
5/83
|
3.0%
1/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Psychiatric disorders
Anxiety
|
4.2%
1/24
|
8.4%
7/83
|
6.1%
2/33
|
16.7%
3/18
|
0.00%
0/18
|
|
Psychiatric disorders
Confusional state
|
4.2%
1/24
|
8.4%
7/83
|
9.1%
3/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Psychiatric disorders
Depression
|
16.7%
4/24
|
2.4%
2/83
|
18.2%
6/33
|
11.1%
2/18
|
0.00%
0/18
|
|
Psychiatric disorders
Hallucination
|
4.2%
1/24
|
1.2%
1/83
|
3.0%
1/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Psychiatric disorders
Insomnia
|
4.2%
1/24
|
12.0%
10/83
|
3.0%
1/33
|
0.00%
0/18
|
16.7%
3/18
|
|
Psychiatric disorders
Mental status changes
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Renal and urinary disorders
Dysuria
|
4.2%
1/24
|
2.4%
2/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Renal and urinary disorders
Haematuria
|
4.2%
1/24
|
4.8%
4/83
|
0.00%
0/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Renal and urinary disorders
Micturition urgency
|
4.2%
1/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Renal and urinary disorders
Pollakiuria
|
8.3%
2/24
|
2.4%
2/83
|
0.00%
0/33
|
11.1%
2/18
|
0.00%
0/18
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/24
|
3.6%
3/83
|
6.1%
2/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Reproductive system and breast disorders
Genital rash
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Reproductive system and breast disorders
Perineal pain
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Reproductive system and breast disorders
Vaginal inflammation
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
11.1%
2/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial fistula
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
6/24
|
15.7%
13/83
|
12.1%
4/33
|
16.7%
3/18
|
38.9%
7/18
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
25.0%
6/24
|
22.9%
19/83
|
21.2%
7/33
|
27.8%
5/18
|
27.8%
5/18
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
25.0%
6/24
|
9.6%
8/83
|
12.1%
4/33
|
11.1%
2/18
|
11.1%
2/18
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
25.0%
6/24
|
2.4%
2/83
|
9.1%
3/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/24
|
2.4%
2/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/24
|
4.8%
4/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Hypoventilation
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/24
|
2.4%
2/83
|
6.1%
2/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
4.2%
1/24
|
2.4%
2/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
12.5%
3/24
|
7.2%
6/83
|
15.2%
5/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
4.2%
1/24
|
2.4%
2/83
|
9.1%
3/33
|
27.8%
5/18
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
4.2%
1/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/24
|
2.4%
2/83
|
6.1%
2/33
|
5.6%
1/18
|
11.1%
2/18
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/24
|
6.0%
5/83
|
6.1%
2/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
4.2%
1/24
|
6.0%
5/83
|
3.0%
1/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
4.2%
1/24
|
1.2%
1/83
|
3.0%
1/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Rhonchi
|
12.5%
3/24
|
3.6%
3/83
|
3.0%
1/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
8.3%
2/24
|
1.2%
1/83
|
0.00%
0/33
|
16.7%
3/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Sputum discoloured
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
12.5%
3/24
|
4.8%
4/83
|
6.1%
2/33
|
11.1%
2/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
58.3%
14/24
|
41.0%
34/83
|
24.2%
8/33
|
0.00%
0/18
|
16.7%
3/18
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/24
|
2.4%
2/83
|
9.1%
3/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Dermal cyst
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
12.5%
3/24
|
8.4%
7/83
|
6.1%
2/33
|
0.00%
0/18
|
16.7%
3/18
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/24
|
1.2%
1/83
|
6.1%
2/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
12.5%
3/24
|
4.8%
4/83
|
6.1%
2/33
|
11.1%
2/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
0.00%
0/24
|
0.00%
0/83
|
6.1%
2/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Onychomadesis
|
4.2%
1/24
|
0.00%
0/83
|
6.1%
2/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
8.3%
2/24
|
2.4%
2/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/24
|
0.00%
0/83
|
6.1%
2/33
|
0.00%
0/18
|
11.1%
2/18
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
12.5%
3/24
|
10.8%
9/83
|
9.1%
3/33
|
11.1%
2/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.00%
0/24
|
0.00%
0/83
|
3.0%
1/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.8%
5/24
|
19.3%
16/83
|
12.1%
4/33
|
22.2%
4/18
|
11.1%
2/18
|
|
Skin and subcutaneous tissue disorders
Rash follicular
|
0.00%
0/24
|
1.2%
1/83
|
3.0%
1/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
4.2%
1/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/24
|
6.0%
5/83
|
0.00%
0/33
|
11.1%
2/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
4.2%
1/24
|
2.4%
2/83
|
3.0%
1/33
|
5.6%
1/18
|
5.6%
1/18
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.00%
0/24
|
0.00%
0/83
|
9.1%
3/33
|
11.1%
2/18
|
11.1%
2/18
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
4.2%
1/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
11.1%
2/18
|
|
Skin and subcutaneous tissue disorders
Skin hypertrophy
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Vascular disorders
Deep vein thrombosis
|
4.2%
1/24
|
4.8%
4/83
|
3.0%
1/33
|
5.6%
1/18
|
16.7%
3/18
|
|
Vascular disorders
Flushing
|
16.7%
4/24
|
2.4%
2/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Vascular disorders
Hot flush
|
0.00%
0/24
|
6.0%
5/83
|
0.00%
0/33
|
0.00%
0/18
|
5.6%
1/18
|
|
Vascular disorders
Hypertension
|
0.00%
0/24
|
1.2%
1/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
|
Vascular disorders
Hypotension
|
12.5%
3/24
|
14.5%
12/83
|
18.2%
6/33
|
11.1%
2/18
|
22.2%
4/18
|
|
Vascular disorders
Orthostatic hypotension
|
8.3%
2/24
|
2.4%
2/83
|
3.0%
1/33
|
0.00%
0/18
|
0.00%
0/18
|
|
Vascular disorders
Pallor
|
0.00%
0/24
|
0.00%
0/83
|
0.00%
0/33
|
5.6%
1/18
|
0.00%
0/18
|
Additional Information
Vice President, Clinical Research
TetraLogic Pharmaceuticals
Phone: 610-889-9900
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place