Trial Outcomes & Findings for A Study of Belinostat + Carboplatin or Paclitaxel or Both in Patients With Ovarian Cancer in Need of Relapse Treatment (NCT NCT00421889)
NCT ID: NCT00421889
Last Updated: 2015-07-28
Results Overview
To determine the maximum tolerated dose of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin (AUC of 5) and paclitaxel (175 mg/m2).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
80 participants
Primary outcome timeframe
Cycle 1
Results posted on
2015-07-28
Participant Flow
Participant milestones
| Measure |
Part A: Dose Escalation 600/5/NA
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 (area under the curve) administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 0 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/NA/175
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/5/175
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 800/5/175
PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 1000/5/175
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
5
|
5
|
3
|
4
|
6
|
35
|
4
|
3
|
15
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
4
|
|
Overall Study
NOT COMPLETED
|
5
|
5
|
3
|
4
|
6
|
35
|
4
|
2
|
11
|
Reasons for withdrawal
| Measure |
Part A: Dose Escalation 600/5/NA
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 (area under the curve) administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 0 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/NA/175
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/5/175
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 800/5/175
PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 1000/5/175
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
1
|
1
|
1
|
4
|
1
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
3
|
0
|
0
|
2
|
0
|
0
|
0
|
0
|
|
Overall Study
Death
|
0
|
0
|
0
|
0
|
1
|
1
|
0
|
0
|
0
|
|
Overall Study
Progressive disease
|
3
|
2
|
2
|
3
|
2
|
21
|
3
|
1
|
5
|
|
Overall Study
Patient/Investigator request
|
0
|
0
|
0
|
0
|
0
|
9
|
0
|
1
|
3
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
A Study of Belinostat + Carboplatin or Paclitaxel or Both in Patients With Ovarian Cancer in Need of Relapse Treatment
Baseline characteristics by cohort
| Measure |
Part A: Dose Escalation 600/5/NA
n=5 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 0 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/NA/175
n=5 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/5/175
n=3 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 800/5/175
n=4 Participants
PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 1000/5/175
n=6 Participants
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD
n=35 Participants
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer
n=4 Participants
PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer
n=3 Participants
PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD
n=15 Participants
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
Total
n=80 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
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
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
22 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
3 Participants
n=24 Participants
|
8 Participants
n=42 Participants
|
59 Participants
n=42 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
13 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
7 Participants
n=42 Participants
|
21 Participants
n=42 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
35 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
1 Participants
n=24 Participants
|
4 Participants
n=42 Participants
|
52 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
2 Participants
n=24 Participants
|
11 Participants
n=42 Participants
|
28 Participants
n=42 Participants
|
PRIMARY outcome
Timeframe: Cycle 1To determine the maximum tolerated dose of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin (AUC of 5) and paclitaxel (175 mg/m2).
Outcome measures
| Measure |
Part A
n=23 Participants
Belinostat: Dose escalating up to 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: administered in an intravenous infusion 2-3 hours after PXD101 infusion on day 3 of a 21 day cycle Carboplatin: administered in an intravenous infusion after paclitaxel on day 3 of a 21 day cycle
|
Part A: Dose Escalation 600/NA/175
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/5/175
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 800/5/175
PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 1000/5/175
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|---|---|---|---|---|
|
Maximum Tolerable Dose (MTD) Belinostat, Part A,
|
1000 mg/m2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1To determine the number of participants experiencing dose limiting toxicities of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin and paclitaxel or both.
Outcome measures
| Measure |
Part A
n=23 Participants
Belinostat: Dose escalating up to 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: administered in an intravenous infusion 2-3 hours after PXD101 infusion on day 3 of a 21 day cycle Carboplatin: administered in an intravenous infusion after paclitaxel on day 3 of a 21 day cycle
|
Part A: Dose Escalation 600/NA/175
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/5/175
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 800/5/175
PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 1000/5/175
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|---|---|---|---|---|
|
Dose Limiting Toxicities (DLT), Part A
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Throughout study until PD (progressive disease) or lost to follow upPopulation: Primary efficacy analysis population, includes all patients who have been enrolled into the study and received at least one dose of study medication.
Best overall responses were assessed by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Clinical tumor evaluation will take place after each cycle. Formal radiological evaluation after every 2 cycles. If a response is noted, a follow-up radiographic assessment must be performed 4 weeks (+ 1 week) after the response is noted
Outcome measures
| Measure |
Part A
n=5 Participants
Belinostat: Dose escalating up to 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: administered in an intravenous infusion 2-3 hours after PXD101 infusion on day 3 of a 21 day cycle Carboplatin: administered in an intravenous infusion after paclitaxel on day 3 of a 21 day cycle
|
Part A: Dose Escalation 600/NA/175
n=5 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/5/175
n=3 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 800/5/175
n=4 Participants
PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 1000/5/175
n=6 Participants
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD
n=35 Participants
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer
n=4 Participants
PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer
n=3 Participants
PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD
n=15 Participants
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|---|---|---|---|---|
|
Best Overall Response (CR or PR)
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
15 participants
|
0 participants
|
0 participants
|
4 participants
|
SECONDARY outcome
Timeframe: Throughout the studyPopulation: Histone acetylase analysis was planned, but not successful due to technical issues with the method.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Throughout studyPopulation: Per protocol Population, includes all patients who have received at least two cycles (complete treatment days, dose reductions per protocol allowed) of study treatment and who have also had at least one post-baseline tumor assessment. Not done for Part A.
Time to progression, defined as the interval between the first dates of treatment until the first notation of disease progression. RECIST criteria
Outcome measures
| Measure |
Part A
n=30 Participants
Belinostat: Dose escalating up to 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: administered in an intravenous infusion 2-3 hours after PXD101 infusion on day 3 of a 21 day cycle Carboplatin: administered in an intravenous infusion after paclitaxel on day 3 of a 21 day cycle
|
Part A: Dose Escalation 600/NA/175
n=6 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/5/175
n=14 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 800/5/175
PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 1000/5/175
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|---|---|---|---|---|
|
Time to Progression
|
195 days
Interval 165.0 to 225.0
|
150 days
Interval 57.0 to
Too few observations
|
136 days
Interval 123.0 to
Too few observations
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Throughout studyPopulation: Includes patients with response, i.e. 15 patients in Part B, 0 patients in Part C, and 4 patients in Part D. Not done for Part A.
Time to response (RECIST) was assessed as the interval between the first dates of treatment until the first notation of response.
Outcome measures
| Measure |
Part A
n=15 Participants
Belinostat: Dose escalating up to 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: administered in an intravenous infusion 2-3 hours after PXD101 infusion on day 3 of a 21 day cycle Carboplatin: administered in an intravenous infusion after paclitaxel on day 3 of a 21 day cycle
|
Part A: Dose Escalation 600/NA/175
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/5/175
n=4 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 800/5/175
PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 1000/5/175
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|---|---|---|---|---|
|
Time to Response
|
NA days
Interval 35.0 to
Insufficient number of participants with events
|
—
|
NA days
Interval 29.0 to
Insufficient number of participants with events
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Throughout studyPopulation: Includes patients with response, i.e. 15 patients in Part B, 0 patients in Part C, and 4 patients in Part D. Not done for Part A.
Defined as interval from the time criteria for CR or PR are met, until the first date that recurrent or progressive disease is objectively documented.
Outcome measures
| Measure |
Part A
n=15 Participants
Belinostat: Dose escalating up to 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: administered in an intravenous infusion 2-3 hours after PXD101 infusion on day 3 of a 21 day cycle Carboplatin: administered in an intravenous infusion after paclitaxel on day 3 of a 21 day cycle
|
Part A: Dose Escalation 600/NA/175
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/5/175
n=4 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 800/5/175
PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 1000/5/175
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|---|---|---|---|---|
|
Duration of Response
|
NA days
Interval 79.0 to
Insufficient number of participants with events
|
—
|
NA days
Interval 56.0 to
Insufficient number of participants with events
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24hPopulation: The Pharmacokinetic Analysis Subset consisted of 41 patients who enrolled in the study and provided a complete or partial set of pharmacokinetic parameters.
Outcome measures
| Measure |
Part A
n=12 Participants
Belinostat: Dose escalating up to 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: administered in an intravenous infusion 2-3 hours after PXD101 infusion on day 3 of a 21 day cycle Carboplatin: administered in an intravenous infusion after paclitaxel on day 3 of a 21 day cycle
|
Part A: Dose Escalation 600/NA/175
n=4 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/5/175
n=18 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 800/5/175
n=4 Participants
PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 1000/5/175
n=3 Participants
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|---|---|---|---|---|
|
Belinostat Cmax
|
18592 ng/mL
Standard Deviation 4390
|
22525 ng/mL
Standard Deviation 6002
|
31517 ng/mL
Standard Deviation 12684
|
8340 ng/mL
Standard Deviation 635
|
2873 ng/mL
Standard Deviation 210
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24hPopulation: The Pharmacokinetic Analysis Subset consisted of 39 patients who enrolled in the study and provided a complete or partial set of pharmacokinetic parameters
Outcome measures
| Measure |
Part A
n=11 Participants
Belinostat: Dose escalating up to 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: administered in an intravenous infusion 2-3 hours after PXD101 infusion on day 3 of a 21 day cycle Carboplatin: administered in an intravenous infusion after paclitaxel on day 3 of a 21 day cycle
|
Part A: Dose Escalation 600/NA/175
n=4 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/5/175
n=18 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 800/5/175
n=4 Participants
PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 1000/5/175
n=2 Participants
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|---|---|---|---|---|
|
Belinostat Mean t½
|
1.41 hours
Standard Deviation 0.58
|
1.16 hours
Standard Deviation 0.133
|
0.898 hours
Standard Deviation 0.161
|
3.76 hours
Standard Deviation 2.9
|
1.9 hours
Standard Deviation 0.286
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24hPopulation: The Pharmacokinetic Analysis Subset consisted of 39 patients who enrolled in the study and provided a complete or partial set of pharmacokinetic parameters.
Outcome measures
| Measure |
Part A
n=11 Participants
Belinostat: Dose escalating up to 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: administered in an intravenous infusion 2-3 hours after PXD101 infusion on day 3 of a 21 day cycle Carboplatin: administered in an intravenous infusion after paclitaxel on day 3 of a 21 day cycle
|
Part A: Dose Escalation 600/NA/175
n=4 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 600/5/175
n=18 Participants
PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 800/5/175
n=4 Participants
PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part A: Dose Escalation 1000/5/175
n=2 Participants
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer
PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|---|---|---|---|---|
|
Belinostat AUC (0-infinity)
|
9116 ng*h/mL
Standard Deviation 1670
|
11785 ng*h/mL
Standard Deviation 2445
|
21057 ng*h/mL
Standard Deviation 11034
|
31515 ng*h/mL
Standard Deviation 3612
|
13107 ng*h/mL
Standard Deviation 1004
|
—
|
—
|
—
|
—
|
Adverse Events
Part A: Dose Escalation (N=23)
Serious events: 17 serious events
Other events: 23 other events
Deaths: 0 deaths
Part B: Ovarian Cancer MTD (N=35)
Serious events: 19 serious events
Other events: 35 other events
Deaths: 0 deaths
Part C: 3-6 Hours Infusion (N=7)
Serious events: 7 serious events
Other events: 7 other events
Deaths: 0 deaths
Part D: Bladder Cancer MTD (N=15)
Serious events: 7 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part A: Dose Escalation (N=23)
n=23 participants at risk
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD (N=35)
n=35 participants at risk
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3-6 Hours Infusion (N=7)
n=7 participants at risk
PXD: 1000 mg/m² was administered as a 3 or 6 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD (N=15)
n=15 participants at risk
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
8.7%
2/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Hepatobiliary disorders
Bile Duct Stenosis
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Infections and infestations
Central Line Infection
|
8.7%
2/23
|
2.9%
1/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Infections and infestations
Clostridium Difficile Colitis
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Vascular disorders
Deep Vein Thrombosis
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
General disorders
Disease Progression
|
13.0%
3/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Immune system disorders
Drug Hypersensitivity
|
4.3%
1/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.0%
3/23
|
0.00%
0/35
|
0.00%
0/7
|
13.3%
2/15
|
|
Investigations
ECG Signs Of Myocardial Ischaemia
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Investigations
Electrocardiogram QT Corrected Interval Prolonged
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Flank Pain
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Haematemesis
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Renal and urinary disorders
Haematuria
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases To Lung
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Nervous system disorders
Sedation
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Infections and infestations
Thrombophlebitis Septic
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Infections and infestations
Urinary Tract Infection
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Vomiting
|
4.3%
1/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
General disorders
Chest Pain
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
13.3%
2/15
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/23
|
2.9%
1/35
|
14.3%
1/7
|
0.00%
0/15
|
|
General disorders
General Physical Health Deterioration
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Blood and lymphatic system disorders
Haemorrhagic Disorder
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Nervous system disorders
Headache
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Vascular disorders
Ischaemia
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Small Intestinal Obstruction
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/23
|
2.9%
1/35
|
28.6%
2/7
|
0.00%
0/15
|
|
Vascular disorders
Venous Thrombosis Limb
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
General disorders
Drug Intolerance
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Infections and infestations
Enterococcal Infection
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Exfoliative Rash
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Infections and infestations
Infection
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7 • Number of events 3
|
0.00%
0/15
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7 • Number of events 1
|
0.00%
0/15
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7 • Number of events 1
|
0.00%
0/15
|
|
General disorders
Pyrexia
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7 • Number of events 1
|
0.00%
0/15
|
|
Gastrointestinal disorders
Rectal Stenosis
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7 • Number of events 1
|
0.00%
0/15
|
|
Infections and infestations
Urinary Tract Infection Enterococcal
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7 • Number of events 1
|
0.00%
0/15
|
|
Investigations
Electrocardiogram T Wave Inversion
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Lethargy
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases To Central Nervous System
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
|
Cardiac disorders
Myocardial Ischaemia
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
|
Infections and infestations
Neutropenic Sepsis
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Peripheral Motor Neuropathy
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Spinal Cord Compression
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
|
Renal and urinary disorders
Ureteric Haemorrhage
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
|
Renal and urinary disorders
Urinary Retention
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 2
|
|
Vascular disorders
Vena Cava Thrombosis
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15 • Number of events 1
|
Other adverse events
| Measure |
Part A: Dose Escalation (N=23)
n=23 participants at risk
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part B: Ovarian Cancer MTD (N=35)
n=35 participants at risk
PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3
|
Part C: 3-6 Hours Infusion (N=7)
n=7 participants at risk
PXD: 1000 mg/m² was administered as a 3 or 6 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)
|
Part D: Bladder Cancer MTD (N=15)
n=15 participants at risk
PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3
|
|---|---|---|---|---|
|
Investigations
Electrocardiogram QT corrected interval prolonged
|
8.7%
2/23
|
2.9%
1/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Investigations
White blood cell count increased
|
8.7%
2/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/23
|
20.0%
7/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Investigations
Blood creatinine increased
|
4.3%
1/23
|
20.0%
7/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/23
|
17.1%
6/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Investigations
Blood alkaline phosphatase increased
|
4.3%
1/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Investigations
Blood glucose increased
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Investigations
Blood magnesium decreased
|
4.3%
1/23
|
5.7%
2/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Investigations
Blood cholesterol increased
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Investigations
Electrocardiogram T wave inversion
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Psychiatric disorders
Insomnia
|
17.4%
4/23
|
31.4%
11/35
|
57.1%
4/7
|
6.7%
1/15
|
|
Psychiatric disorders
Anxiety
|
8.7%
2/23
|
14.3%
5/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Psychiatric disorders
Depression
|
8.7%
2/23
|
11.4%
4/35
|
14.3%
1/7
|
6.7%
1/15
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Cardiac disorders
Sinus tachycardia
|
13.0%
3/23
|
8.6%
3/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Cardiac disorders
Palpitations
|
8.7%
2/23
|
8.6%
3/35
|
57.1%
4/7
|
6.7%
1/15
|
|
Cardiac disorders
Sinus bradycardia
|
8.7%
2/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
6.7%
1/15
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Cardiac disorders
Cyanosis
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Excoriation
|
8.7%
2/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Contusion
|
4.3%
1/23
|
8.6%
3/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Radiation skin injury
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Sunburn
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Eye disorders
Vision blurred
|
8.7%
2/23
|
22.9%
8/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Eye disorders
Diplopia
|
0.00%
0/23
|
2.9%
1/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Eye disorders
Dry eye
|
0.00%
0/23
|
2.9%
1/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Eye disorders
Vitreous floaters
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Renal and urinary disorders
Bladder pain
|
8.7%
2/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/23
|
14.3%
5/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Renal and urinary disorders
Pollakiuria
|
4.3%
1/23
|
11.4%
4/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Renal and urinary disorders
Proteinuria
|
4.3%
1/23
|
8.6%
3/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Renal and urinary disorders
Haematuria
|
4.3%
1/23
|
5.7%
2/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Renal and urinary disorders
Dysuria
|
4.3%
1/23
|
11.4%
4/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Renal and urinary disorders
Bladder spasm
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Renal and urinary disorders
Incontinence
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
13.3%
2/15
|
|
Renal and urinary disorders
Micturition urgency
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Renal and urinary disorders
Ureteric haemorrhage
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Renal and urinary disorders
Urethral haemorrhage
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Renal and urinary disorders
Urinary bladder haemorrhage
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Immune system disorders
Drug hypersensitivity
|
8.7%
2/23
|
22.9%
8/35
|
42.9%
3/7
|
26.7%
4/15
|
|
Immune system disorders
Hypersensitivity
|
4.3%
1/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/23
|
2.9%
1/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Ear and labyrinth disorders
Hypoacusis
|
0.00%
0/23
|
8.6%
3/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/23
|
8.6%
3/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Reproductive system and breast disorders
Genital pain
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Reproductive system and breast disorders
Penile pain
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Hepatobiliary disorders
Hepatic pain
|
4.3%
1/23
|
0.00%
0/35
|
28.6%
2/7
|
0.00%
0/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
4.3%
1/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Surgical and medical procedures
Ureteric diversion operation
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Endocrine disorders
Cushingoid
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Gastrointestinal disorders
Nausea
|
69.6%
16/23
|
97.1%
34/35
|
100.0%
7/7
|
73.3%
11/15
|
|
General disorders
Fatigue
|
78.3%
18/23
|
91.4%
32/35
|
100.0%
7/7
|
73.3%
11/15
|
|
General disorders
Oedema Peripheral
|
17.4%
4/23
|
25.7%
9/35
|
14.3%
1/7
|
26.7%
4/15
|
|
General disorders
Pyrexia
|
17.4%
4/23
|
17.1%
6/35
|
100.0%
7/7
|
33.3%
5/15
|
|
General disorders
Chills
|
13.0%
3/23
|
8.6%
3/35
|
0.00%
0/7
|
13.3%
2/15
|
|
General disorders
Disease progression
|
13.0%
3/23
|
0.00%
0/35
|
0.00%
0/7
|
0.00%
0/15
|
|
General disorders
Chest pain
|
0.00%
0/23
|
14.3%
5/35
|
0.00%
0/7
|
13.3%
2/15
|
|
General disorders
Catheter Site Pain
|
4.3%
1/23
|
8.6%
3/35
|
0.00%
0/7
|
0.00%
0/15
|
|
General disorders
Mucosal Inflammation
|
0.00%
0/23
|
8.6%
3/35
|
0.00%
0/7
|
13.3%
2/15
|
|
General disorders
Chest Discomfort
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
General disorders
Face Oedema
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
General disorders
Localised Oedema
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
General disorders
Pain
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
General disorders
Drug intolerance
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
General disorders
Influenza like illness
|
4.3%
1/23
|
0.00%
0/35
|
14.3%
1/7
|
13.3%
2/15
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
26.7%
4/15
|
|
General disorders
Catheter site phlebitis
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
6.7%
1/15
|
|
General disorders
Injection site reaction
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Gastrointestinal disorders
Constipation
|
60.9%
14/23
|
57.1%
20/35
|
100.0%
7/7
|
80.0%
12/15
|
|
Gastrointestinal disorders
Vomiting
|
60.9%
14/23
|
71.4%
25/35
|
71.4%
5/7
|
53.3%
8/15
|
|
Gastrointestinal disorders
Diarrhoea
|
47.8%
11/23
|
71.4%
25/35
|
57.1%
4/7
|
60.0%
9/15
|
|
Gastrointestinal disorders
Abdominal pain
|
17.4%
4/23
|
48.6%
17/35
|
28.6%
2/7
|
6.7%
1/15
|
|
Gastrointestinal disorders
Abdominal distension
|
13.0%
3/23
|
31.4%
11/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Dyspepsia
|
13.0%
3/23
|
28.6%
10/35
|
42.9%
3/7
|
13.3%
2/15
|
|
Gastrointestinal disorders
Stomatitis
|
13.0%
3/23
|
0.00%
0/35
|
71.4%
5/7
|
26.7%
4/15
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/23
|
11.4%
4/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Dry mouth
|
4.3%
1/23
|
8.6%
3/35
|
42.9%
3/7
|
6.7%
1/15
|
|
Gastrointestinal disorders
Small intestine obstruction
|
0.00%
0/23
|
8.6%
3/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Abdominal pain lower
|
4.3%
1/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Ascites
|
4.3%
1/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Gastrooesophagela reflux disease
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/23
|
5.7%
2/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/23
|
5.7%
2/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Dysphagia
|
4.3%
1/23
|
0.00%
0/35
|
14.3%
1/7
|
6.7%
1/15
|
|
Gastrointestinal disorders
Lip blister
|
0.00%
0/23
|
2.9%
1/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Oral mucosal blistering
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
6.7%
1/15
|
|
Gastrointestinal disorders
Rectal stenosis
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Blood and lymphatic system disorders
Anaemia
|
60.9%
14/23
|
68.6%
24/35
|
85.7%
6/7
|
53.3%
8/15
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
17.4%
4/23
|
42.9%
15/35
|
28.6%
2/7
|
6.7%
1/15
|
|
Blood and lymphatic system disorders
Neutropenia
|
13.0%
3/23
|
45.7%
16/35
|
28.6%
2/7
|
33.3%
5/15
|
|
Blood and lymphatic system disorders
Leukopenia
|
4.3%
1/23
|
40.0%
14/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
4.3%
1/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
39.1%
9/23
|
31.4%
11/35
|
71.4%
5/7
|
40.0%
6/15
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
39.1%
9/23
|
34.3%
12/35
|
71.4%
5/7
|
26.7%
4/15
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
21.7%
5/23
|
25.7%
9/35
|
28.6%
2/7
|
26.7%
4/15
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
13.0%
3/23
|
22.9%
8/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
13.0%
3/23
|
5.7%
2/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
8.7%
2/23
|
2.9%
1/35
|
0.00%
0/7
|
13.3%
2/15
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
8.7%
2/23
|
0.00%
0/35
|
0.00%
0/7
|
20.0%
3/15
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.7%
2/23
|
22.9%
8/35
|
14.3%
1/7
|
20.0%
3/15
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/23
|
11.4%
4/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/23
|
11.4%
4/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
4.3%
1/23
|
11.4%
4/35
|
0.00%
0/7
|
13.3%
2/15
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
4.3%
1/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Tenosynovitis
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
43.5%
10/23
|
71.4%
25/35
|
85.7%
6/7
|
66.7%
10/15
|
|
Nervous system disorders
Headache
|
39.1%
9/23
|
34.3%
12/35
|
100.0%
7/7
|
40.0%
6/15
|
|
Nervous system disorders
Dizziness
|
26.1%
6/23
|
42.9%
15/35
|
57.1%
4/7
|
6.7%
1/15
|
|
Nervous system disorders
Dysgeusia
|
26.1%
6/23
|
48.6%
17/35
|
14.3%
1/7
|
13.3%
2/15
|
|
Nervous system disorders
Paraesthesia
|
8.7%
2/23
|
2.9%
1/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Nervous system disorders
Coordination abnormal
|
0.00%
0/23
|
8.6%
3/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Nervous system disorders
Syncope
|
0.00%
0/23
|
8.6%
3/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Nervous system disorders
Migraine
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/23
|
2.9%
1/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Nervous system disorders
Lethargy
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
20.0%
3/15
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
20.0%
3/15
|
|
Nervous system disorders
Neurotoxicity
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
13.3%
2/15
|
|
Nervous system disorders
Dyskinesia
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Nervous system disorders
Nervous system disorder
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Nervous system disorders
Sciatica
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Nervous system disorders
Spinal cord compression
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Nervous system disorders
Tremor
|
4.3%
1/23
|
2.9%
1/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
56.5%
13/23
|
74.3%
26/35
|
85.7%
6/7
|
73.3%
11/15
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
8.7%
2/23
|
5.7%
2/35
|
28.6%
2/7
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
8.7%
2/23
|
5.7%
2/35
|
14.3%
1/7
|
20.0%
3/15
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.7%
2/23
|
17.1%
6/35
|
14.3%
1/7
|
20.0%
3/15
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.3%
1/23
|
22.9%
8/35
|
42.9%
3/7
|
33.3%
5/15
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.00%
0/23
|
8.6%
3/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
0.00%
0/23
|
5.7%
2/35
|
14.3%
1/7
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Acne
|
4.3%
1/23
|
0.00%
0/35
|
28.6%
2/7
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Exfoliative rash
|
4.3%
1/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/23
|
2.9%
1/35
|
14.3%
1/7
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
43.5%
10/23
|
31.4%
11/35
|
71.4%
5/7
|
46.7%
7/15
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.4%
4/23
|
28.6%
10/35
|
42.9%
3/7
|
33.3%
5/15
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
17.4%
4/23
|
11.4%
4/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
8.7%
2/23
|
11.4%
4/35
|
14.3%
1/7
|
20.0%
3/15
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
4.3%
1/23
|
14.3%
5/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/23
|
8.6%
3/35
|
28.6%
2/7
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/23
|
8.6%
3/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
4.3%
1/23
|
5.7%
2/35
|
14.3%
1/7
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/23
|
2.9%
1/35
|
14.3%
1/7
|
20.0%
3/15
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
4.3%
1/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract haemorrhage
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Vascular disorders
Flushing
|
52.2%
12/23
|
42.9%
15/35
|
100.0%
7/7
|
26.7%
4/15
|
|
Vascular disorders
Deep vein thrombosis
|
8.7%
2/23
|
8.6%
3/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Vascular disorders
Hypertension
|
8.7%
2/23
|
8.6%
3/35
|
14.3%
1/7
|
40.0%
6/15
|
|
Vascular disorders
Hot flush
|
0.00%
0/23
|
11.4%
4/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Vascular disorders
Hypotension
|
0.00%
0/23
|
11.4%
4/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Vascular disorders
Phlebitis
|
4.3%
1/23
|
2.9%
1/35
|
0.00%
0/7
|
13.3%
2/15
|
|
Vascular disorders
Diastolic hypertension
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Vascular disorders
Embolism
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Vascular disorders
Vena cava thrombosis
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Anorexia
|
43.5%
10/23
|
34.3%
12/35
|
100.0%
7/7
|
53.3%
8/15
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
4.3%
1/23
|
31.4%
11/35
|
14.3%
1/7
|
13.3%
2/15
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/23
|
25.7%
9/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/23
|
22.9%
8/35
|
28.6%
2/7
|
20.0%
3/15
|
|
Metabolism and nutrition disorders
Dehydration
|
4.3%
1/23
|
20.0%
7/35
|
28.6%
2/7
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/23
|
20.0%
7/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/23
|
14.3%
5/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
4.3%
1/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Diabetes mellitus non-insulin-dependent
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Infections and infestations
Urinary tract infection
|
13.0%
3/23
|
25.7%
9/35
|
0.00%
0/7
|
33.3%
5/15
|
|
Infections and infestations
Central line infection
|
8.7%
2/23
|
2.9%
1/35
|
0.00%
0/7
|
13.3%
2/15
|
|
Infections and infestations
Oral candidiasis
|
8.7%
2/23
|
8.6%
3/35
|
14.3%
1/7
|
6.7%
1/15
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/23
|
14.3%
5/35
|
28.6%
2/7
|
0.00%
0/15
|
|
Infections and infestations
Candidiasis
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/23
|
5.7%
2/35
|
0.00%
0/7
|
0.00%
0/15
|
|
Infections and infestations
Infection
|
0.00%
0/23
|
0.00%
0/35
|
28.6%
2/7
|
0.00%
0/15
|
|
Infections and infestations
Bacteriaemia
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Infections and infestations
Cystitis
|
4.3%
1/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Infections and infestations
Enterococcal infection
|
0.00%
0/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Infections and infestations
Urinary tract infection enterococcal
|
4.3%
1/23
|
0.00%
0/35
|
14.3%
1/7
|
0.00%
0/15
|
|
Infections and infestations
Cellulitis
|
4.3%
1/23
|
0.00%
0/35
|
0.00%
0/7
|
13.3%
2/15
|
|
Infections and infestations
Pneumonia
|
4.3%
1/23
|
2.9%
1/35
|
0.00%
0/7
|
13.3%
2/15
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Infections and infestations
Localised infection
|
0.00%
0/23
|
2.9%
1/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Infections and infestations
Neutropenic sepsis
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/23
|
0.00%
0/35
|
0.00%
0/7
|
6.7%
1/15
|
|
Investigations
Weight decreased
|
13.0%
3/23
|
2.9%
1/35
|
28.6%
2/7
|
0.00%
0/15
|
|
Investigations
Blood potassium decreased
|
8.7%
2/23
|
2.9%
1/35
|
14.3%
1/7
|
6.7%
1/15
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60