Trial Outcomes & Findings for PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinase 3 (FLT3) (CPKC412A2104E1 and CPKC412A2104E2) (NCT NCT00045942)
NCT ID: NCT00045942
Last Updated: 2017-08-11
Results Overview
Best clinical response was defined as complete response (CR) or partial response (PR), according to NCI definitions for AML and the guidelines for defining responses in MDS.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
144 participants
Primary outcome timeframe
from date of first patient first visit (FPFV), 29-Jan-2002, to date of last participant last visit (LPLV), 04-Sep-2003
Results posted on
2017-08-11
Participant Flow
In PKC412A2104 (Core), FLT3 mutated participants with AML or MDS received open-label PKC412. In PKC412A2104E1, FLT3 mutated participants and FLT3 wild type participants were randomized to receive either PKC412 50 mg bid or PKC412 100 mg bid.
In PKC412A2104E2, participants were alternately assigned to the regimens, beginning with the first enrolled into the intra-patient dose escalation arm and the next enrolled into the PKC412 + itraconazole arm. Of the 16 participants enrolled in the PKC412 dose escalation arm, 14 were newly enrolled, and 2 were transitioned from PKC412A2104E1.
Participant milestones
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 Dose Escalation (E2)
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
|
FLT3 Mutated PKC+Itraconazole (E2)
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
|
FLT3 Wild Type PKC412 Dose Escalation (E2)
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
|
FLT3 Wild Type PKC+Itraconazole (E2)
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
|
|---|---|---|---|---|---|---|---|---|---|
|
PKC412A2104 (Core)
STARTED
|
20
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
PKC412A2104 (Core)
Core Primary Efficacy
|
20
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
PKC412A2104 (Core)
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
PKC412A2104 (Core)
NOT COMPLETED
|
20
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
PKC412A2104E1
STARTED
|
0
|
18
|
17
|
33
|
27
|
0
|
0
|
0
|
0
|
|
PKC412A2104E1
Primary Efficacy
|
0
|
18
|
17
|
32
|
25
|
0
|
0
|
0
|
0
|
|
PKC412A2104E1
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
PKC412A2104E1
NOT COMPLETED
|
0
|
18
|
17
|
33
|
27
|
0
|
0
|
0
|
0
|
|
PKC412A2104E2
STARTED
|
0
|
0
|
0
|
0
|
0
|
9
|
7
|
7
|
6
|
|
PKC412A2104E2
Primary Efficacy
|
0
|
0
|
0
|
0
|
0
|
9
|
7
|
7
|
6
|
|
PKC412A2104E2
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
PKC412A2104E2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
9
|
7
|
7
|
6
|
Reasons for withdrawal
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 Dose Escalation (E2)
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
|
FLT3 Mutated PKC+Itraconazole (E2)
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
|
FLT3 Wild Type PKC412 Dose Escalation (E2)
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
|
FLT3 Wild Type PKC+Itraconazole (E2)
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
|
|---|---|---|---|---|---|---|---|---|---|
|
PKC412A2104 (Core)
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
PKC412A2104 (Core)
Adverse Event
|
5
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
PKC412A2104 (Core)
Lack of Efficacy
|
13
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
PKC412A2104 (Core)
Death
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
PKC412A2104E1
Withdrawal by Subject
|
0
|
0
|
2
|
5
|
2
|
0
|
0
|
0
|
0
|
|
PKC412A2104E1
Condition no longer requires study drug
|
0
|
1
|
1
|
0
|
1
|
0
|
0
|
0
|
0
|
|
PKC412A2104E1
Lack of Efficacy
|
0
|
11
|
11
|
23
|
17
|
0
|
0
|
0
|
0
|
|
PKC412A2104E1
Abnormal laboratory value
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
PKC412A2104E1
Adverse Event
|
0
|
1
|
1
|
3
|
6
|
0
|
0
|
0
|
0
|
|
PKC412A2104E1
Death
|
0
|
4
|
1
|
1
|
1
|
0
|
0
|
0
|
0
|
|
PKC412A2104E1
Enrolled into PKC412A2104E2
|
0
|
0
|
1
|
1
|
0
|
0
|
0
|
0
|
0
|
|
PKC412A2104E2
Lost to Follow-up
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
3
|
0
|
|
PKC412A2104E2
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
1
|
0
|
|
PKC412A2104E2
Lack of Efficacy
|
0
|
0
|
0
|
0
|
0
|
3
|
2
|
2
|
6
|
|
PKC412A2104E2
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
4
|
3
|
1
|
0
|
|
PKC412A2104E2
Death
|
0
|
0
|
0
|
0
|
0
|
1
|
2
|
0
|
0
|
Baseline Characteristics
PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinase 3 (FLT3) (CPKC412A2104E1 and CPKC412A2104E2)
Baseline characteristics by cohort
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=20 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 100 mg/Day (E1)
n=18 Participants
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
n=17 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
n=33 Participants
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
n=27 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 Dose Escalation (E2)
n=8 Participants
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
|
FLT3 Mutated PKC+Itraconazole (E2)
n=7 Participants
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
|
FLT3 Wild Type PKC412 Dose Escalation (E2)
n=6 Participants
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
|
FLT3 Wild Type PKC+Itraconazole (E2)
n=6 Participants
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
|
Total
n=142 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
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
5 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
56 Participants
n=42 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
6 Participants
n=24 Participants
|
6 Participants
n=42 Participants
|
86 Participants
n=42 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
4 Participants
n=24 Participants
|
4 Participants
n=42 Participants
|
66 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
2 Participants
n=24 Participants
|
2 Participants
n=42 Participants
|
76 Participants
n=42 Participants
|
PRIMARY outcome
Timeframe: from date of first patient first visit (FPFV), 29-Jan-2002, to date of last participant last visit (LPLV), 04-Sep-2003Population: Core primary efficacy population: The core primary efficacy population included all participants who were randomized.
Best clinical response was defined as complete response (CR) or partial response (PR), according to NCI definitions for AML and the guidelines for defining responses in MDS.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=20 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Number of Participants With Best Clinical Response (Core)
|
0 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: days 1, 28Population: This outcome measure was not analyzed. Assessment of FLT3 autophosphorylation in leukemic blasts was not possible at the planned time points because the blast reduction was rapid and occurred during the first week in some participants. Thus, by Day 28, the blast count in some participants were too low for autophosphorylation to be measured.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004Population: E1 primary efficacy population: all participants who received at least one dose of study medication, completed at least 8 days of therapy within Cycle 1 unless discontinued due to progressive disease and/or death due to any cause, and who were not considered to be associated with a protocol violation that was exclusionary from the population.
Overall clinical response was defined as CR, PR, minor response (MR) or blast response (BR). CR and PR was defined according to NCI definitions, and MR and BR was defined according to the guidelines for defining hematologic improvement in MDS.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=18 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
n=17 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
n=32 Participants
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
n=25 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Number of Participants With Overall Clinical Response (E1)
Complete response
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Overall Clinical Response (E1)
Partial response
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Overall Clinical Response (E1)
Minor response
|
1 Participants
|
0 Participants
|
6 Participants
|
3 Participants
|
|
Number of Participants With Overall Clinical Response (E1)
Blast response
|
11 Participants
|
12 Participants
|
15 Participants
|
8 Participants
|
|
Number of Participants With Overall Clinical Response (E1)
Overall response
|
12 Participants
|
13 Participants
|
21 Participants
|
11 Participants
|
PRIMARY outcome
Timeframe: days 1, 28Population: The analyses for this outcome measure were not performed due to technical challenges in measuring phosphorylated FLT3 in patient blast samples in an ex vivo setting.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Days 1, 28Population: The analyses for this outcome measure were not performed due to technical challenges in measuring phosphorylated FLT3 in patient blast samples in an ex vivo setting.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Cycle 1: days 21, 22, 28Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for pharmacokinetic (PK) analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for PKC412 Plasma in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 21 (n=9)
|
22261.53 h*ng/ml
Standard Deviation 11984.6
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for PKC412 Plasma in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 22 (n=10)
|
37578.85 h*ng/ml
Standard Deviation 44330.7
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for PKC412 Plasma in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 28 (n=7)
|
35630.45 h*ng/ml
Standard Deviation 23993.2
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 21, 22, 28Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for pharmacokinetic (PK) analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for PKC412 in the PKC + Itraconazole Combination Arm (E2)
Cycle 1 , day 21 (n=10)
|
3945.00 ng/ml
Standard Deviation 4440.238
|
—
|
—
|
—
|
|
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for PKC412 in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 22 (n=10)
|
3968.70 ng/ml
Standard Deviation 4047.498
|
—
|
—
|
—
|
|
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for PKC412 in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 28 (n=8)
|
3931.25 ng/ml
Standard Deviation 2638.135
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 21, 22, 28Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for PK analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 21 (n=10)
|
1.6 hour
Interval 1.0 to 8.1
|
—
|
—
|
—
|
|
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 22 (n=10)
|
1.9 hour
Interval 1.2 to 4.7
|
—
|
—
|
—
|
|
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 28 (n=8)
|
2.2 hour
Interval 0.0 to 3.3
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 21, 22, 28Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for PK analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 21 (n=10)
|
32120.58 h*ng/ml
Standard Deviation 35792.2
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 22 (n=10)
|
34684.6 h*ng/ml
Standard Deviation 37084.9
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 28, (n=8)
|
33020.17 h*ng/ml
Standard Deviation 17206.3
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 21 and 22Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for PK analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=8 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Terminal Elimination Half-life (T1/2) for PKC412 in the PKC + Itrconazole Combination Arm (E2)
Cycle 1, day 21 (n=6)
|
18.13 hour
Standard Deviation 13.505
|
—
|
—
|
—
|
|
Terminal Elimination Half-life (T1/2) for PKC412 in the PKC + Itrconazole Combination Arm (E2)
Cycle 1, day 22 (n=8)
|
13.23 hour
Standard Deviation 6.346
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 21, 22, 28Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for pharmacokinetic (PK) analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=8 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP62221 Plasma in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 21 (n=8)
|
30217.82 h*ng/ml
Standard Deviation 16502.90
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP62221 Plasma in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 22 (n=7)
|
23824.69 h*ng/ml
Standard Deviation 13300.69
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP62221 Plasma in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 28 (n=7)
|
31545.54 h*ng/ml
Standard Deviation 12453.16
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 21, 22, 28Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for pharmacokinetic (PK) analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP62221 in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 21 (n=10)
|
3259.30 ng/ml
Standard Deviation 1747.923
|
—
|
—
|
—
|
|
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP62221 in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 22 (n=10)
|
3221.40 ng/ml
Standard Deviation 1980.217
|
—
|
—
|
—
|
|
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP62221 in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 28 (n=8)
|
3032.25 ng/ml
Standard Deviation 1975.371
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 21, 22, 28Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for PK analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP62221 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 21 (n=10)
|
3.7 hour
Interval 0.0 to 10.3
|
—
|
—
|
—
|
|
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP62221 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 22 (n=10)
|
2.3 hour
Interval 0.0 to 6.1
|
—
|
—
|
—
|
|
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP62221 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 28 (n=8)
|
3.3 hour
Interval 0.0 to 8.5
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 21, 22, 28Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for PK analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP622221 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 21 (n=10)
|
31699.93 h*ng/ml
Standard Deviation 15573.87
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP622221 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 22 (n=10)
|
31182.90 h*ng/ml
Standard Deviation 17380.39
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP622221 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 28 (n=8)
|
26688.60 h*ng/ml
Standard Deviation 10901.40
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: day 22,Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For this end point, 4 participants with non-missing values were analyzed.
Blood samples were collected for PK analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=4 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Terminal Elimination Half-life (T1/2) for CGP62221 in the PKC + Itrconazole Combination Arm (E2)
|
14.37 hour
Standard Deviation 6.743
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 21, 22, 28Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for pharmacokinetic (PK) analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=9 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP52421 Plasma in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 21 (n=9)
|
40258.65 h*ng/ml
Standard Deviation 9747.374
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP52421 Plasma in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 22 (n=7)
|
42950.76 h*ng/ml
Standard Deviation 8604.972
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP52421 Plasma in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 28 (n=7)
|
49758.77 h*ng/ml
Standard Deviation 7733.621
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 21, 22, 28Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for pharmacokinetic (PK) analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP52421 in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 21 (n=10)
|
4173.00 ng/ml
Standard Deviation 985.473
|
—
|
—
|
—
|
|
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP52421 in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 22 (n=10)
|
4293.00 ng/ml
Standard Deviation 1292.380
|
—
|
—
|
—
|
|
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP52421 in the PKC + Itraconazole Combination Arm (E2)
Cycle 1, day 28 (n=8)
|
4875.00 ng/ml
Standard Deviation 1376.382
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 21, 22, 28Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for PK analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 21 (n=10)
|
3.5 hour
Interval 0.0 to 6.5
|
—
|
—
|
—
|
|
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 22 (n=10)
|
2.1 hour
Interval 0.0 to 10.7
|
—
|
—
|
—
|
|
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 28 (n=8)
|
2.2 hour
Interval 0.0 to 8.3
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 21, 22, 28Population: The pharmacokinetic (PK) population in the midostaurin + itraconazole FLT3 mutated and FLT3 wild-type combined arms, which consisted of 10 participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for PK analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 21 (n=10)
|
38899.84 h*ng/ml
Standard Deviation 7616.481
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 22 (n=10)
|
41035.50 h*ng/ml
Standard Deviation 10807.22
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1, day 28 (n=8)
|
44447.05 h*ng/ml
Standard Deviation 8906.006
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 1, 2 (24 hr post day 1), 3, 8, 15, 16 (24 hr post day 15), 17, 22; Cycle 2: days 1, 2 (24 hr post day 1), 3, 8, 15Population: The PK analysis set of the FLT3 mutated PKC412 dose escalation and FLT3 wild type PKC412 dose escalation combined arms, which consisted of the 14 newly enrolled participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=12 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 1, day 1 (=7)
|
0 ng/ml
Interval 0.0 to 0.0
|
—
|
—
|
—
|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 1, day 2 (24 hours post day 1) (n=12)
|
2565.0 ng/ml
Interval 1170.0 to 7250.0
|
—
|
—
|
—
|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 1, day 3 (n=12)
|
3100.0 ng/ml
Interval 1340.0 to 9080.0
|
—
|
—
|
—
|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 1, day 8 (n=8)
|
1640.0 ng/ml
Interval 1030.0 to 4340.0
|
—
|
—
|
—
|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 1, day 15 (n=6)
|
744.5 ng/ml
Interval 549.0 to 7080.0
|
—
|
—
|
—
|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 1, day 16 (24 hr post day 15) (n=6)
|
836.0 ng/ml
Interval 669.0 to 9120.0
|
—
|
—
|
—
|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 1, day 17 (n=5)
|
800.0 ng/ml
Interval 710.0 to 982.0
|
—
|
—
|
—
|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 1, day 22 (n=5)
|
1410.0 ng/ml
Interval 595.0 to 6270.0
|
—
|
—
|
—
|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 2, day 1 (n=4)
|
772.0 ng/ml
Interval 667.0 to 2670.0
|
—
|
—
|
—
|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 2, day 2 (24 hr post day 1) (n=4)
|
1141.0 ng/ml
Interval 516.0 to 6410.0
|
—
|
—
|
—
|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 2, day3 (n=4)
|
1295.0 ng/ml
Interval 610.0 to 7450.0
|
—
|
—
|
—
|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 2, day 8 (n=4)
|
1210.0 ng/ml
Interval 727.0 to 1420.0
|
—
|
—
|
—
|
|
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 2, day 15 (n=3)
|
834.0 ng/ml
Interval 515.0 to 1000.0
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 1, 2 (24 hr post day 1), 3, 8, 15, 16 (24 hr post day 15), 17, 22; Cycle 2: days 1, 2 (24 hr post day 1), 3, 8, 15Population: The PK analysis set of the FLT3 mutated PKC412 dose escalation and FLT3 wild type PKC412 dose escalation combined arms, which consisted of the 14 newly enrolled participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=12 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Summary of CGP62221 Concentration (E2)
Cycle 1, day 1 (n=7)
|
0 ng/ml
Interval 0.0 to 0.0
|
—
|
—
|
—
|
|
Summary of CGP62221 Concentration (E2)
Cycle 1, day 2 (24 hr post day 1) (n=12)
|
1320.0 ng/ml
Interval 570.0 to 2720.0
|
—
|
—
|
—
|
|
Summary of CGP62221 Concentration (E2)
Cycle 1, day 3 (n=12)
|
2750.0 ng/ml
Interval 1800.0 to 4340.0
|
—
|
—
|
—
|
|
Summary of CGP62221 Concentration (E2)
Cycle 1, day 8 (n=8)
|
2380.0 ng/ml
Interval 2000.0 to 7380.0
|
—
|
—
|
—
|
|
Summary of CGP62221 Concentration (E2)
Cycle 1, day 15 (n=6)
|
1505.0 ng/ml
Interval 1110.0 to 4630.0
|
—
|
—
|
—
|
|
Summary of CGP62221 Concentration (E2)
Cycle 1, day 16 (24 hr post day 15) (n=6)
|
1425.0 ng/ml
Interval 1190.0 to 5390.0
|
—
|
—
|
—
|
|
Summary of CGP62221 Concentration (E2)
Cycle 1, day 17 (n=5)
|
1480.0 ng/ml
Interval 1200.0 to 1710.0
|
—
|
—
|
—
|
|
Summary of CGP62221 Concentration (E2)
Cycle 1, day 22 (n=5)
|
1520.0 ng/ml
Interval 1410.0 to 3330.0
|
—
|
—
|
—
|
|
Summary of CGP62221 Concentration (E2)
Cycle 2, day 1 (n=4)
|
1545.0 ng/ml
Interval 1350.0 to 3210.0
|
—
|
—
|
—
|
|
Summary of CGP62221 Concentration (E2)
Cycle 2, day 2 (24 hr post day 1) (n=4)
|
1945.0 ng/ml
Interval 880.0 to 3430.0
|
—
|
—
|
—
|
|
Summary of CGP62221 Concentration (E2)
Cycle 2, day 3 (n=4)
|
2070.0 ng/ml
Interval 1260.0 to 3430.0
|
—
|
—
|
—
|
|
Summary of CGP62221 Concentration (E2)
Cycle 2, day 8 (n=4)
|
2030.0 ng/ml
Interval 1620.0 to 2360.0
|
—
|
—
|
—
|
|
Summary of CGP62221 Concentration (E2)
Cycle 2, day 15 (n=3)
|
1740.0 ng/ml
Interval 1360.0 to 1790.0
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1: days 1, 2 (24 hr post day 1), 3, 8, 15, 16 (24 hr post day 15), 17, 22; Cycle 2: days 1, 2 (24 hr post day 1), 3, 8, 15Population: The PK analysis set of the FLT3 mutated PKC412 dose escalation and FLT3 wild type PKC412 dose escalation combined arms, which consisted of the 14 newly enrolled participants, was considered for the analysis. For each time point, participants of the PK analysis set with non-missing values were analyzed.
Blood samples were collected for analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=12 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Summary of CGP52421 Concentration (E2)
Cycle 2, day 15 (n=3)
|
4030.0 ng/ml
Interval 3370.0 to 5780.0
|
—
|
—
|
—
|
|
Summary of CGP52421 Concentration (E2)
Cycle 1, day 1 (n=7)
|
0 ng/ml
Interval 0.0 to 0.0
|
—
|
—
|
—
|
|
Summary of CGP52421 Concentration (E2)
Cycle 1, day 2 (24 hr post day 1) (n=12)
|
684.0 ng/ml
Interval 0.0 to 1100.0
|
—
|
—
|
—
|
|
Summary of CGP52421 Concentration (E2)
Cycle 1, day 3 (n=12)
|
1185.0 ng/ml
Interval 1020.0 to 1860.0
|
—
|
—
|
—
|
|
Summary of CGP52421 Concentration (E2)
Cycle 1, day 8 (n=8)
|
2835.0 ng/ml
Interval 2230.0 to 3950.0
|
—
|
—
|
—
|
|
Summary of CGP52421 Concentration (E2)
Cycle 1, day 15 (n=6)
|
3845.0 ng/ml
Interval 1810.0 to 6110.0
|
—
|
—
|
—
|
|
Summary of CGP52421 Concentration (E2)
Cycle 1, day 16 (24 hr post day 15) (n=6)
|
3830.0 ng/ml
Interval 1830.0 to 6070.0
|
—
|
—
|
—
|
|
Summary of CGP52421 Concentration (E2)
Cycle 1, day 17 (n=5)
|
3620.0 ng/ml
Interval 2120.0 to 4560.0
|
—
|
—
|
—
|
|
Summary of CGP52421 Concentration (E2)
Cycle 1, day 22 (n=5)
|
4470.0 ng/ml
Interval 1860.0 to 8500.0
|
—
|
—
|
—
|
|
Summary of CGP52421 Concentration (E2)
Cycle 2, day 1 (n=4)
|
4915.0 ng/ml
Interval 379.0 to 6590.0
|
—
|
—
|
—
|
|
Summary of CGP52421 Concentration (E2)
Cycle 2, day 2 (24 hr post day 1) (n=4)
|
4455.0 ng/ml
Interval 185.0 to 9610.0
|
—
|
—
|
—
|
|
Summary of CGP52421 Concentration (E2)
Cycle 2, day 3 (n=4)
|
4470.0 ng/ml
Interval 3150.0 to 5210.0
|
—
|
—
|
—
|
|
Summary of CGP52421 Concentration (E2)
Cycle 2, day 8 (n=4)
|
4860.0 ng/ml
Interval 3500.0 to 5570.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: from date of FPFV, 29-Jan-2002, to date of LPLV, 04-Sep-2003Population: Core primary efficacy population: The core primary efficacy population included all participants who were randomized.
TTP was defined as the time from first dose date to date of disease progression which is identified as study completion date for unsatisfactory treatment effect or date of death from any cause within the 28 day cutoff post treatment.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=20 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Time to Disease Progression (TTP) (Core)
|
63.0 days
Interval 26.0 to 92.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1,Population: The Core PK analysis set, which consisted of 15 participants, was considered for the analysis. For each time point, only participants of the PK set who had non-missing values were analyzed.
Blood samples were collected for analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Summary of Midostaurin Plasma Concentration (Core)
Cycle 1, day 1(24 hour) (n=10)
|
3801.0 ng/ml
Standard Deviation 2529.069
|
—
|
—
|
—
|
|
Summary of Midostaurin Plasma Concentration (Core)
Cycle 1, day 3 (n=7)
|
7152.86 ng/ml
Standard Deviation 4254.173
|
—
|
—
|
—
|
|
Summary of Midostaurin Plasma Concentration (Core)
Cycle 1, day 8 (n=9)
|
5154.44 ng/ml
Standard Deviation 5004.511
|
—
|
—
|
—
|
|
Summary of Midostaurin Plasma Concentration (Core)
Cycle 2, day 1 (n=6)
|
1873.17 ng/ml
Standard Deviation 1521.685
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1,Population: The Core PK analysis set, which consisted of 15 participants, were considered for the analysis. For each time point, only participants of the PK set who had non-missing values were analyzed.
Blood samples were collected for analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Summary of CGP62221 Plasma Concentration (Core)
Cycle 1, day 1 (24 hour) (n=10)
|
1636.00 ng/ml
Standard Deviation 612.938
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration (Core)
Cycle 1, day 3 (n=7)
|
3143.71 ng/ml
Standard Deviation 1147.407
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration (Core)
Cycle 1, day 8 (n=9)
|
4873.33 ng/ml
Standard Deviation 3421.593
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration (Core)
Cycle 2, day 1 (n=6)
|
2816.67 ng/ml
Standard Deviation 2095.850
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1,Population: The Core PK analysis set, which consisted of 15 participants, were considered for the analysis. For each time point, only participants of the PK set who had non-missing values were analyzed.
Blood samples were collected for analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=10 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Summary of CGP52421 Plasma Concentration (Core)
Cycle 1, day 1 (24 hour) (n=10)
|
951.70 ng/ml
Standard Deviation 297.866
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration (Core)
Cycle 1, day 3 (n=7)
|
1846.57 ng/ml
Standard Deviation 657.472
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration (Core)
Cycle 1, day 8 (n=9)
|
6342.22 ng/ml
Standard Deviation 2586.440
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration (Core)
Cycle 2, day 1 (n=6)
|
12978.33 ng/ml
Standard Deviation 4036.436
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004Population: Primary efficacy population: defined as all patients who received at least 1 dose of study medication, completed at least eight days of therapy within Cycle 1 unless discontinued due to progressive disease and/or death due to any cause, and who were not considered to be associated with a protocol violation that was exclusionary from the population.
TTP was defined as the time from the first dose date to the date of disease progression (defined as the study completion date for unsatisfactory treatment effect, date of response assessment of progressive disease, or date of death from any cause). One participant from the wild type 200 mg group did not have any assessment on treatment and therefore was not taken into account for TTP.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=18 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
n=17 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
n=32 Participants
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
n=25 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Time to Disease Progression (E1)
|
77.0 days
Interval 36.0 to 109.0
|
50.0 days
Interval 24.0 to 63.0
|
62.0 days
Interval 30.0 to 82.0
|
54.0 days
Interval 29.0 to 84.0
|
SECONDARY outcome
Timeframe: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004Population: Primary efficacy population: defined as all patients who received at least 1 dose of study medication, completed at least eight days of therapy within Cycle 1 unless discontinued due to progressive disease and/or death due to any cause, and who were not considered to be associated with a protocol violation that was exclusionary from the population.
OS was measured from the date of the first dose of treatment to the date of death from any cause or to the last date that the patient was known to be alive (a censored observation).
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=18 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
n=17 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
n=32 Participants
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
n=25 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Overall Survival (OS) (E1)
|
99.0 days
Interval 61.0 to 120.0
|
93.0 days
Interval 52.0 to 139.0
|
145.0 days
Interval 75.0 to 257.0
|
159.0 days
Interval 98.0 to 313.0
|
SECONDARY outcome
Timeframe: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004Population: Responders from the PEP; PEP defined as all patients who received at least 1 dose of study medication, completed at least 8 days of therapy within Cycle 1 unless discontinued due to progressive disease and/or death due to any cause, and who were not considered to be associated with a protocol violation that was exclusionary from the population.
Duration of best clinical response was measured from the time that the measurement criteria were met for CR, PR, MR (with or without blast reduction) or BR until the first date that recurrent disease was documented (event) or until the date of last follow up.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=12 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
n=13 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
n=21 Participants
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
n=11 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Duration of Best Clinical Response (E1)
|
57.0 days
Interval 8.0 to 86.0
|
29.0 days
Interval 4.0 to 35.0
|
56.0 days
Interval 29.0 to 78.0
|
58.0 days
Interval 9.0 to 192.0
|
SECONDARY outcome
Timeframe: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004Population: Primary efficacy population: defined as all patients who received at least 1 dose of study medication, completed at least eight days of therapy within Cycle 1 unless discontinued due to progressive disease and/or death due to any cause, and who were not considered to be associated with a protocol violation that was exclusionary from the population.
Event-free survival was defined as the time from date of start of treatment to the date of death from any cause, treatment failure or relapse
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=18 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
n=17 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
n=32 Participants
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
n=25 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Event-free Survival (E1)
|
60.0 days
Interval 1.0 to 109.0
|
50.0 days
Interval 1.0 to 63.0
|
58.0 days
Interval 1.0 to 82.0
|
1.0 days
Interval 1.0 to 42.0
|
SECONDARY outcome
Timeframe: Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h)Population: The PK population of the mutated PKC412 100 mg/day and wild type PKC412 100 mg/day arms combined, which consisted of all participants who provided at least one evaluable PK sample and received at least one dose of study treatment, was considered for the analysis. For each time point, only participants with non-missing values were analyzed..
Blood samples were collected for analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=43 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Summary of PKC412 Plasma Concentration for 50 mg Twice Daily (Bid) Arm (E1)
Cycle 1, day 1 (0h) (n=43)
|
0.000 ng/ml
Standard Deviation 0.0000
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 50 mg Twice Daily (Bid) Arm (E1)
Cycle 1, day 1 (4h) (n=38)
|
1198.000 ng/ml
Standard Deviation 522.4766
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 50 mg Twice Daily (Bid) Arm (E1)
Cycle 1, day 1 (24h) (n=39)
|
1735.974 ng/ml
Standard Deviation 1161.933
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 50 mg Twice Daily (Bid) Arm (E1)
Cycle 1, day 3 (0h) (n=34)
|
2585.471 ng/ml
Standard Deviation 1843.852
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 50 mg Twice Daily (Bid) Arm (E1)
Cycle 1, day 8 (0h) (n=30)
|
3576.467 ng/ml
Standard Deviation 3263.112
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 50 mg Twice Daily (Bid) Arm (E1)
Cycle 2, day 1 (0h) (n=22)
|
1756.500 ng/ml
Standard Deviation 1695.327
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 50 mg Twice Daily (Bid) Arm (E1)
Cycle 3, day 1 (0h) (n=12)
|
2038.417 ng/ml
Standard Deviation 2079.252
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 50 mg Twice Daily (Bid) Arm (E1)
Cycle 4, day 1 (0h) (n=4)
|
820.750 ng/ml
Standard Deviation 565.0247
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h)Population: The PK population of the mutated PKC412 100 mg/day and wild type PKC412 100 mg/day arms combined, which consisted of all participants who provided at least one evaluable PK sample and received at least one dose of study treatment, was considered for the analysis. For each time point, only participants with non-missing values were analyzed..
Blood samples were collected for analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=44 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Summary of CGP62221 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 1, day 1 (0h) (n=44)
|
0.000 ng/ml
Standard Deviation 0.0000
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 1, day 1 (4h) (n=38)
|
367.079 ng/ml
Standard Deviation 220.2728
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 1, day 1 (24h) (n=39)
|
808.182 ng/ml
Standard Deviation 375.4818
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 1, day 3 (0h) (n=34)
|
1400.476 ng/ml
Standard Deviation 681.9106
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 1, day 8 (0h) (n=30)
|
2868.933 ng/ml
Standard Deviation 1723.985
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 2, day 1 (0h) (n=22)
|
1930.000 ng/ml
Standard Deviation 1241.980
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 3, day 1 (0h) (n=12)
|
1971.500 ng/ml
Standard Deviation 1519.628
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 4, day 1 (0h) (n=4)
|
1207.500 ng/ml
Standard Deviation 310.5238
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h)Population: The PK population of the mutated PKC412 100 mg/day and wild type PKC412 100 mg/day arms combined, which consisted of all participants who provided at least one evaluable PK sample and received at least one dose of study treatment, was considered for the analysis. For each time point, only participants with non-missing values were analyzed..
Blood samples were collected for analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=41 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Summary of CGP52421 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 1, day 1 (0h) (n=41)
|
0.000 ng/ml
Standard Deviation 0.0000
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 1, day 1 (4h) (n=38)
|
203.013 ng/ml
Standard Deviation 121.3817
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 1, day 1 (24h) (n=39)
|
436.282 ng/ml
Standard Deviation 210.1306
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 50 mg Bid Arm (E1)
Day 1, day 3 (0h) (n=34)
|
1188.359 ng/ml
Standard Deviation 1833.644
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 1, day 8 (0h) (n=30)
|
2840.833 ng/ml
Standard Deviation 1158.132
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 2, day 1 (0h) (n=22)
|
6467.591 ng/ml
Standard Deviation 3434.776
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 3, day 1 (0h) (n=12)
|
8175.000 ng/ml
Standard Deviation 4851.968
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 50 mg Bid Arm (E1)
Cycle 4, day 1 (0h) (n=4)
|
6205.000 ng/ml
Standard Deviation 1619.084
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h); cycle 5: day 1 (0h) and cycle 6: day 1 (0h)Population: The PK population of the mutated PKC412 200 mg/day and wild type PKC412 200 mg/day arms combined, which consisted of all participants who provided at least one evaluable PK sample and received at least one dose of study treatment, was considered for the analysis. For each time point, only participants with non-missing values were analyzed..
Blood samples were collected for analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=38 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 1 (0h) (n=38)
|
0.000 ng/ml
Standard Deviation 0.0000
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 1 (4h) (n=34)
|
2087.088 ng/ml
Standard Deviation 1087.277
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 1 (24h) (n=36)
|
2849.731 ng/ml
Standard Deviation 2150.176
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 3 (0h) (n=29)
|
3756.483 ng/ml
Standard Deviation 2549.759
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 8 (0h) (n=24)
|
4447.583 ng/ml
Standard Deviation 4233.285
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 2, day 1 (0h) (n=15)
|
1226.333 ng/ml
Standard Deviation 894.1562
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 3, day 2 (0h) (n=6)
|
754.500 ng/ml
Standard Deviation 264.6860
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 4, day 1 (0h) (n=6)
|
1187.167 ng/ml
Standard Deviation 1026.004
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 5, day 1 (0h) (n=4)
|
572.250 ng/ml
Standard Deviation 314.7405
|
—
|
—
|
—
|
|
Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 6, day 1 (0h) (n=4)
|
1433.250 ng/ml
Standard Deviation 1670.029
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h); cycle 5: day 1 (0h) and cycle 6: day 1 (0h)Population: The PK population of the mutated PKC412 200 mg/day and wild type PKC412 200 mg/day arms combined, which consisted of all participants who provided at least one evaluable PK sample and received at least one dose of study treatment, was considered for the analysis. For each time point, only participants with non-missing values were analyzed..
Blood samples were collected for analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=39 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 1 (0h) (n=39)
|
0.000 ng/ml
Standard Deviation 0.0000
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 1 (4h) (n=34)
|
471.635 ng/ml
Standard Deviation 342.7850
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 1 (24h) (n=36)
|
1134.764 ng/ml
Standard Deviation 655.1779
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 3 (0h) (n=29)
|
1944.069 ng/ml
Standard Deviation 1049.770
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 8 (0h) (n=24)
|
2898.708 ng/ml
Standard Deviation 1876.446
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 2, day 1 (0h) (n=15)
|
1828.667 ng/ml
Standard Deviation 650.1524
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 3, day 2 (0h) (n=6)
|
1258.333 ng/ml
Standard Deviation 289.0271
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 4, day 1 (0h) (n=6)
|
1602.950 ng/ml
Standard Deviation 1071.167
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 5, day 1 (0h) (n4)
|
1111.250 ng/ml
Standard Deviation 357.8728
|
—
|
—
|
—
|
|
Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 6, day 1 (0h) (n=4)
|
1662.500 ng/ml
Standard Deviation 864.4603
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h); cycle 5: day 1 (0h) and cycle 6: day 1 (0h)Population: The PK population of the mutated PKC412 200 mg/day and wild type PKC412 200 mg/day arms combined, which consisted of all participants who provided at least one evaluable PK sample and received at least one dose of study treatment, was considered for the analysis. For each time point, only participants with non-missing values were analyzed..
Blood samples were collected for analysis.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=38 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 3 (0h) (n=29)
|
1394.062 ng/ml
Standard Deviation 653.2943
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 1 (0h) (n=38)
|
0.000 ng/ml
Standard Deviation 0.0000
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 1 (4h) (n=34)
|
257.391 ng/ml
Standard Deviation 148.6420
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 1 (24h) (n=36)
|
666.194 ng/ml
Standard Deviation 313.5770
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 1, day 8 (0h) (n=24)
|
4447.500 ng/ml
Standard Deviation 1359.192
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 2, day 1 (0h) (n=15)
|
9196.667 ng/ml
Standard Deviation 3248.590
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 3, day 2 (0h) (n=6)
|
8811.667 ng/ml
Standard Deviation 3376.172
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 4, day 1 (0h) (n=6)
|
6266.667 ng/ml
Standard Deviation 3895.452
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 5, day 1 (0h) (n4)
|
7845.000 ng/ml
Standard Deviation 4078.313
|
—
|
—
|
—
|
|
Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)
Cycle 6, day 1 (0h) (n=4)
|
8710.000 ng/ml
Standard Deviation 4890.774
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: date of FPFV, 21-Aug-2003, to date of LPLV, 27-Mar-2008Population: The primary efficacy population, which included all participants, who received at least one dose of study drug and who completed at least 8 days of treatment in Cycle 1, unless they discontinued due to progressive disease and/or death due to any cause, and who did not experience any protocol violations, was analyzed..
Best clinical response was defined as CR, PR, MR, MR+BR, or BR . CR and PR was defined according to NCI definitions, and MR and BR was defined according to the guidelines for defining hematologic improvement in MDS.
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=9 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
n=7 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
n=7 Participants
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
n=6 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Best Clinical Response (E2)
Complete response
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Best Clinical Response (E2)
Partial response
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Best Clinical Response (E2)
Minor response
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Best Clinical Response (E2)
Minor response and blast response
|
1 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
|
Best Clinical Response (E2)
Blast response
|
4 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Best Clinical Response (E2)
Best clinical response
|
5 Participants
|
0 Participants
|
2 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: date of FPFV, 21-Aug-2003, to date of LPLV, 27-Mar-2008Population: The primary efficacy population, which included all participants, who received at least one dose of study drug and who completed at least 8 days of treatment in Cycle 1, unless they discontinued due to progressive disease and/or death due to any cause, and who did not experience any protocol violations, was analyzed..
TTP was defined as the time from the first dose date to the date of disease progression, which was defined as the study completion date for unsatisfactory treatment effect, the date of response assessment of progressive disease, or the date of death from any cause
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=9 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
n=7 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
n=7 Participants
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
n=6 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Time to Disease Progression (E2)
|
49.0 days
Interval 11.0 to 222.0
|
26.0 days
Interval 12.0 to 50.0
|
169.0 days
Interval 113.0 to 370.0
|
78.0 days
Interval 29.0 to 1348.0
|
SECONDARY outcome
Timeframe: date of FPFV, 21-Aug-2003, to date of LPLV, 27-Mar-2008Population: The primary efficacy population, which included all participants, who received at least one dose of study drug and who completed at least 8 days of treatment in Cycle 1, unless they discontinued due to progressive disease and/or death due to any cause, and who did not experience any protocol violations, was analyzed..
OS was measured from the date of the first dose of treatment to the date of death from any cause or the last date the patient was known to be alive (censored observation)
Outcome measures
| Measure |
PKC412 in FLT3 Mutated Participants (Core)
n=9 Participants
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
n=7 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
n=7 Participants
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
n=6 Participants
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
|---|---|---|---|---|
|
Overall Survival (E2)
|
116.0 days
Interval 11.0 to 222.0
|
75.0 days
Interval 26.0 to 194.0
|
372.0 days
Interval 276.0 to
The upper 95% confidence interval could not be calculated.
|
220.0 days
Interval 64.0 to
The upper 95% confidence interval could not be calculated.
|
Adverse Events
PKC412 Core
Serious events: 12 serious events
Other events: 20 other events
Deaths: 0 deaths
FLT3 Mutated PKC412 100 mg/Day (E1)
Serious events: 16 serious events
Other events: 17 other events
Deaths: 0 deaths
FLT3 Mutated PKC412 200 mg/Day (E1)
Serious events: 14 serious events
Other events: 16 other events
Deaths: 0 deaths
FLT3 Wild Type PKC412 100 mg/Day (E1)
Serious events: 22 serious events
Other events: 32 other events
Deaths: 0 deaths
FLT3 Wild Type PKC412 200 mg/Day (E1)
Serious events: 19 serious events
Other events: 27 other events
Deaths: 0 deaths
FLT3 Mutated PKC412 Dose Escalation (E2)
Serious events: 7 serious events
Other events: 9 other events
Deaths: 0 deaths
FLT3 Mutated PKC+Itraconazole (E2)
Serious events: 6 serious events
Other events: 6 other events
Deaths: 0 deaths
FLT3 Wild Type PKC412 Dose Escalation (E2)
Serious events: 5 serious events
Other events: 7 other events
Deaths: 0 deaths
FLT3 Wild Type PKC+Itraconazole (E2)
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PKC412 Core
n=20 participants at risk
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 100 mg/Day (E1)
n=18 participants at risk
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
n=17 participants at risk
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
n=33 participants at risk
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
n=27 participants at risk
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 Dose Escalation (E2)
n=9 participants at risk
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
|
FLT3 Mutated PKC+Itraconazole (E2)
n=7 participants at risk
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
|
FLT3 Wild Type PKC412 Dose Escalation (E2)
n=7 participants at risk
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
|
FLT3 Wild Type PKC+Itraconazole (E2)
n=6 participants at risk
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
|
|---|---|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
6.1%
2/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
22.2%
2/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Congenital, familial and genetic disorders
Aplasia
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Eye disorders
Blindness
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Eye disorders
Erythema of eyelid
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
9.1%
3/33
|
11.1%
3/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Anaemia NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Anaemia haemolytic autoimmune
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
15.0%
3/20
|
16.7%
3/18
|
17.6%
3/17
|
27.3%
9/33
|
18.5%
5/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
33.3%
2/6
|
|
Blood and lymphatic system disorders
Leukocytosis
|
10.0%
2/20
|
5.6%
1/18
|
5.9%
1/17
|
3.0%
1/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.0%
1/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Splenic infarction
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Splenomegaly
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
11.1%
1/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.0%
1/20
|
0.00%
0/18
|
5.9%
1/17
|
9.1%
3/33
|
11.1%
3/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
6.1%
2/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
16.7%
1/6
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Aortic valve incompetence
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Atrioventricular block
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Cardiac aneurysm
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Cardiac disorders
Cardiac arrest
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Cardiac failure acute
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Cardiomegaly
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gastric polyps
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
6.1%
2/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Intestinal prolapse
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Pneumatosis intestinalis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Polyp colorectal
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/20
|
0.00%
0/18
|
11.8%
2/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Asthenia
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
General disorders
Chest discomfort
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Chest pain
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Chills
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Disease progression
|
0.00%
0/20
|
11.1%
2/18
|
5.9%
1/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Drug interaction
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Fatigue
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
6.1%
2/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
General physical health deterioration
|
0.00%
0/20
|
5.6%
1/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
16.7%
1/6
|
|
General disorders
Injection site cellulitis
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Lethargy
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Mucosal inflammation
|
0.00%
0/20
|
5.6%
1/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Multi-organ failure
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Performance status decreased
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Pyrexia
|
10.0%
2/20
|
5.6%
1/18
|
5.9%
1/17
|
15.2%
5/33
|
22.2%
6/27
|
44.4%
4/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Hepatobiliary disorders
Cholelithiasis
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Hepatobiliary disorders
Gallbladder disorder
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Hepatobiliary disorders
Hepatocellular damage
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Hepatobiliary disorders
Hepatomegaly
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Hepatobiliary disorders
Liver disorder
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Acute sinusitis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Arthritis infective
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Aspergillosis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Bacterial sepsis
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Bronchopneumonia NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Candida sepsis
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Candidiasis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Catheter bacteraemia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Cellulitis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Central line infection
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Enterococcal bacteraemia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Enterococcal sepsis
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Erysipelas
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Gangrene
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Infections and infestations
Gastrointestinal infection
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Infection
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Lobar pneumonia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Mastoiditis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Mycobacterium avium complex infection
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Neutropenic infection
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Perianal abscess
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Pneumonia
|
0.00%
0/20
|
27.8%
5/18
|
5.9%
1/17
|
27.3%
9/33
|
11.1%
3/27
|
11.1%
1/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Infections and infestations
Pneumonia NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Pneumonia fungal
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Pneumonia klebsiella
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Pseudomonal sepsis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Respiratory tract infection NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Sepsis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
14.8%
4/27
|
11.1%
1/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Sepsis NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Septic shock
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Sinusitis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Sinusitis NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Skin infection
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Soft tissue infection NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Thrombophlebitis septic
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Subdural haemorrhage
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/20
|
0.00%
0/18
|
11.8%
2/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/20
|
0.00%
0/18
|
11.8%
2/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Bacteria stool identified
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Blast cell count increased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
28.6%
2/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Investigations
Blood amylase increased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Blood creatinine increased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
6.1%
2/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Blood pressure increased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Investigations
Breath sounds abnormal
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
C-reactive protein increased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Culture urine positive
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Fibrinolysis increased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Investigations
Gram stain positive
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Lipase increased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Platelet count increased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Transaminases increased
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Troponin NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Urine output decreased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
White blood cell count decreased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
White blood cell count increased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
6.1%
2/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Cachexia
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Dehydration
|
5.0%
1/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Diabetes mellitus non-insulin-dependent
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Fluid retention
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Lactic acidosis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Bone infarction
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Coccydynia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.0%
1/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Blast cell crisis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia recurrent
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemic infiltration pulmonary
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukostasis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour lysis syndrome
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Aphasia
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Asterixis
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Coma
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Dizziness
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Facial palsy
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Headache
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Metabolic encephalopathy NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Nervous system disorder
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Neurological symptom
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Somnolence
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Syncope
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Tonic clonic movements
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Psychiatric disorders
Confusional state
|
5.0%
1/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Psychiatric disorders
Delirium
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Reproductive system and breast disorders
Bartholin's cyst
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Reproductive system and breast disorders
Breast pain
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.0%
1/20
|
11.1%
2/18
|
11.8%
2/17
|
6.1%
2/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
20.0%
4/20
|
0.00%
0/18
|
11.8%
2/17
|
6.1%
2/33
|
3.7%
1/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Maxillary sinusitis
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
7.4%
2/27
|
11.1%
1/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary alveolar haemorrhage
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
6.1%
2/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
5.0%
1/20
|
5.6%
1/18
|
5.9%
1/17
|
3.0%
1/33
|
7.4%
2/27
|
11.1%
1/9
|
28.6%
2/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Septal panniculitis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Urticaria NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Vascular disorders
Hypotension
|
0.00%
0/20
|
11.1%
2/18
|
0.00%
0/17
|
0.00%
0/33
|
11.1%
3/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Hypotension NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Venous stasis
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
Other adverse events
| Measure |
PKC412 Core
n=20 participants at risk
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 100 mg/Day (E1)
n=18 participants at risk
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 200 mg/Day (E1)
n=17 participants at risk
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 100 mg/Day (E1)
n=33 participants at risk
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Wild Type PKC412 200 mg/Day (E1)
n=27 participants at risk
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
|
FLT3 Mutated PKC412 Dose Escalation (E2)
n=9 participants at risk
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
|
FLT3 Mutated PKC+Itraconazole (E2)
n=7 participants at risk
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
|
FLT3 Wild Type PKC412 Dose Escalation (E2)
n=7 participants at risk
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
|
FLT3 Wild Type PKC+Itraconazole (E2)
n=6 participants at risk
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
|
|---|---|---|---|---|---|---|---|---|---|
|
Investigations
Aspartate aminotransferase increased
|
10.0%
2/20
|
16.7%
3/18
|
23.5%
4/17
|
0.00%
0/33
|
11.1%
3/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/20
|
16.7%
3/18
|
5.9%
1/17
|
21.2%
7/33
|
11.1%
3/27
|
33.3%
3/9
|
0.00%
0/7
|
57.1%
4/7
|
66.7%
4/6
|
|
Blood and lymphatic system disorders
Anaemia NOS
|
20.0%
4/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
9.1%
3/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.0%
1/20
|
11.1%
2/18
|
5.9%
1/17
|
0.00%
0/33
|
11.1%
3/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Blood and lymphatic system disorders
Leukocytosis
|
10.0%
2/20
|
5.6%
1/18
|
5.9%
1/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
22.2%
2/9
|
0.00%
0/7
|
14.3%
1/7
|
33.3%
2/6
|
|
Blood and lymphatic system disorders
Lymph node pain
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
15.0%
3/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.0%
1/20
|
27.8%
5/18
|
0.00%
0/17
|
12.1%
4/33
|
3.7%
1/27
|
22.2%
2/9
|
0.00%
0/7
|
28.6%
2/7
|
33.3%
2/6
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Splenomegaly
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Thrombocythaemia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
10.0%
2/20
|
27.8%
5/18
|
5.9%
1/17
|
12.1%
4/33
|
14.8%
4/27
|
0.00%
0/9
|
14.3%
1/7
|
14.3%
1/7
|
33.3%
2/6
|
|
Cardiac disorders
Atrial fibrillation
|
5.0%
1/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Bradycardia NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Cardiovascular disorder
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Mitral valve incompetence
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Sinus tachycardia
|
5.0%
1/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/20
|
11.1%
2/18
|
11.8%
2/17
|
0.00%
0/33
|
3.7%
1/27
|
33.3%
3/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Cardiac disorders
Tachycardia NOS
|
15.0%
3/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Ear and labyrinth disorders
Deafness neurosensory
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Ear and labyrinth disorders
Hypoacusis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Ear and labyrinth disorders
Mastoid disorder
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Endocrine disorders
Hyperaldosteronism
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Eye disorders
Eye swelling
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Gastrointestinal disorders
Abdominal distension
|
10.0%
2/20
|
11.1%
2/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/20
|
22.2%
4/18
|
11.8%
2/17
|
0.00%
0/33
|
22.2%
6/27
|
33.3%
3/9
|
0.00%
0/7
|
42.9%
3/7
|
16.7%
1/6
|
|
Gastrointestinal disorders
Abdominal pain NOS
|
15.0%
3/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Anal fissure
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.00%
0/20
|
11.1%
2/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Constipation
|
15.0%
3/20
|
5.6%
1/18
|
29.4%
5/17
|
9.1%
3/33
|
29.6%
8/27
|
11.1%
1/9
|
28.6%
2/7
|
42.9%
3/7
|
33.3%
2/6
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/20
|
27.8%
5/18
|
47.1%
8/17
|
36.4%
12/33
|
55.6%
15/27
|
55.6%
5/9
|
42.9%
3/7
|
57.1%
4/7
|
50.0%
3/6
|
|
Gastrointestinal disorders
Diarrhoea NOS
|
30.0%
6/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Dry mouth
|
5.0%
1/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Dysphagia
|
15.0%
3/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gastric dilatation
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gastric ileus
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.0%
1/20
|
5.6%
1/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gingival bleeding
|
25.0%
5/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gingival pain
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
6.1%
2/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/20
|
0.00%
0/18
|
11.8%
2/17
|
9.1%
3/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Lip ulceration
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Loose stools
|
10.0%
2/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Mouth ulceration
|
10.0%
2/20
|
0.00%
0/18
|
0.00%
0/17
|
9.1%
3/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Gastrointestinal disorders
Nausea
|
70.0%
14/20
|
61.1%
11/18
|
52.9%
9/17
|
57.6%
19/33
|
59.3%
16/27
|
33.3%
3/9
|
42.9%
3/7
|
71.4%
5/7
|
100.0%
6/6
|
|
Gastrointestinal disorders
Neutropenic colitis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Obstruction gastric
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Odynophagia
|
10.0%
2/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Oral discomfort
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Oral mucosal petechiae
|
10.0%
2/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Gastrointestinal disorders
Oral pain
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Gastrointestinal disorders
Perianal erythema
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Rectal tenesmus
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Saliva altered
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Tongue blistering
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Tongue oedema
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/20
|
66.7%
12/18
|
52.9%
9/17
|
39.4%
13/33
|
44.4%
12/27
|
44.4%
4/9
|
28.6%
2/7
|
42.9%
3/7
|
66.7%
4/6
|
|
Gastrointestinal disorders
Vomiting NOS
|
60.0%
12/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Asthenia
|
0.00%
0/20
|
27.8%
5/18
|
17.6%
3/17
|
18.2%
6/33
|
14.8%
4/27
|
0.00%
0/9
|
0.00%
0/7
|
28.6%
2/7
|
33.3%
2/6
|
|
General disorders
Catheter site erythema
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Catheter site pain
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Chest pain
|
0.00%
0/20
|
0.00%
0/18
|
11.8%
2/17
|
9.1%
3/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Chills
|
0.00%
0/20
|
11.1%
2/18
|
5.9%
1/17
|
3.0%
1/33
|
7.4%
2/27
|
22.2%
2/9
|
14.3%
1/7
|
14.3%
1/7
|
16.7%
1/6
|
|
General disorders
Fatigue
|
40.0%
8/20
|
38.9%
7/18
|
35.3%
6/17
|
36.4%
12/33
|
29.6%
8/27
|
33.3%
3/9
|
14.3%
1/7
|
57.1%
4/7
|
33.3%
2/6
|
|
General disorders
Feeling cold
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
General disorders
General physical health deterioration
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Generalised oedema
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
General disorders
Inflammation
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
General disorders
Injection site erythema
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Mucosal inflammation
|
0.00%
0/20
|
16.7%
3/18
|
5.9%
1/17
|
6.1%
2/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Nodule
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Oedema
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
6.1%
2/33
|
11.1%
3/27
|
11.1%
1/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
General disorders
Oedema NOS
|
10.0%
2/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Oedema peripheral
|
40.0%
8/20
|
16.7%
3/18
|
23.5%
4/17
|
24.2%
8/33
|
22.2%
6/27
|
11.1%
1/9
|
14.3%
1/7
|
14.3%
1/7
|
16.7%
1/6
|
|
General disorders
Pain
|
0.00%
0/20
|
11.1%
2/18
|
5.9%
1/17
|
15.2%
5/33
|
7.4%
2/27
|
22.2%
2/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
General disorders
Pain NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Pyrexia
|
35.0%
7/20
|
38.9%
7/18
|
29.4%
5/17
|
21.2%
7/33
|
18.5%
5/27
|
44.4%
4/9
|
14.3%
1/7
|
14.3%
1/7
|
33.3%
2/6
|
|
General disorders
Rigors
|
10.0%
2/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Submandibular mass
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Ulcer
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Hepatobiliary disorders
Hepatic function abnormal NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Hepatobiliary disorders
Hepatic steatosis
|
0.00%
0/20
|
5.6%
1/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Hepatobiliary disorders
Hepatomegaly
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
10.0%
2/20
|
0.00%
0/18
|
11.8%
2/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Immune system disorders
Graft versus host disease
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Abscess
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Infections and infestations
Ano-rectal infection bacterial NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Aspergillosis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Candidal infection NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Candidiasis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Infections and infestations
Carbuncle
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Catheter site infection
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Cellulitis
|
5.0%
1/20
|
0.00%
0/18
|
5.9%
1/17
|
9.1%
3/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Cystitis
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Ear infection
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Infections and infestations
Enterococcal infection
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Folliculitis
|
0.00%
0/20
|
11.1%
2/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Furuncle
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Herpes simplex
|
10.0%
2/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Herpes viral infection NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Infection
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Influenza
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Lung infection
|
0.00%
0/20
|
5.6%
1/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
6.1%
2/33
|
7.4%
2/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Oral herpes
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Pneumonia
|
0.00%
0/20
|
11.1%
2/18
|
17.6%
3/17
|
6.1%
2/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Infections and infestations
Puncture site infection
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Rash pustular
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Rhinitis
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Sepsis
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Sinusitis
|
0.00%
0/20
|
5.6%
1/18
|
5.9%
1/17
|
3.0%
1/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Sinusitis bacterial
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Skin infection
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
28.6%
2/7
|
16.7%
1/6
|
|
Infections and infestations
Upper respiratory tract infection NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
9.1%
3/33
|
14.8%
4/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Infections and infestations
Vaginal candidiasis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Infections and infestations
Viral infection NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Blister
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Blood blister
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Contrast media reaction
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
6.1%
2/33
|
14.8%
4/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/20
|
5.6%
1/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Fall
|
5.0%
1/20
|
0.00%
0/18
|
17.6%
3/17
|
6.1%
2/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Limb injury NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Post procedural pain
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Postoperative haematoma
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Subcutaneous haematoma
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
15.0%
3/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Investigations
Activated partial thromboplastin time prolonged
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Alanine aminotransferase increased
|
10.0%
2/20
|
11.1%
2/18
|
23.5%
4/17
|
0.00%
0/33
|
11.1%
3/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Investigations
Blood alkaline phosphatase increased
|
10.0%
2/20
|
5.6%
1/18
|
11.8%
2/17
|
0.00%
0/33
|
11.1%
3/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Investigations
Blood amylase increased
|
5.0%
1/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
14.3%
1/7
|
16.7%
1/6
|
|
Investigations
Blood bilirubin increased
|
15.0%
3/20
|
16.7%
3/18
|
5.9%
1/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
14.3%
1/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Investigations
Blood creatinine increased
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Investigations
Blood glucose increased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Blood in stool
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Body temperature increased
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Cardiac murmur NOS
|
15.0%
3/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Lipase increased
|
5.0%
1/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Oxygen saturation decreased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Prothrombin time prolonged
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Spleen palpable
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Investigations
Weight decreased
|
5.0%
1/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Investigations
White blood cell count increased
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Acidosis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Alkalosis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Anorexia
|
25.0%
5/20
|
16.7%
3/18
|
11.8%
2/17
|
15.2%
5/33
|
14.8%
4/27
|
0.00%
0/9
|
14.3%
1/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
11.1%
3/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Dehydration
|
10.0%
2/20
|
11.1%
2/18
|
5.9%
1/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Fluid retention
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/20
|
11.1%
2/18
|
17.6%
3/17
|
6.1%
2/33
|
14.8%
4/27
|
0.00%
0/9
|
14.3%
1/7
|
42.9%
3/7
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hyperglycaemia NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
9.1%
3/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
14.3%
1/7
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/20
|
11.1%
2/18
|
17.6%
3/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
5.0%
1/20
|
16.7%
3/18
|
11.8%
2/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
14.3%
1/7
|
14.3%
1/7
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
25.0%
5/20
|
38.9%
7/18
|
35.3%
6/17
|
24.2%
8/33
|
11.1%
3/27
|
33.3%
3/9
|
14.3%
1/7
|
14.3%
1/7
|
33.3%
2/6
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
15.0%
3/20
|
11.1%
2/18
|
11.8%
2/17
|
12.1%
4/33
|
14.8%
4/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.0%
1/20
|
22.2%
4/18
|
17.6%
3/17
|
9.1%
3/33
|
3.7%
1/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
5.0%
1/20
|
5.6%
1/18
|
17.6%
3/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.0%
2/20
|
0.00%
0/18
|
5.9%
1/17
|
9.1%
3/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.0%
3/20
|
11.1%
2/18
|
5.9%
1/17
|
9.1%
3/33
|
11.1%
3/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
10.0%
2/20
|
5.6%
1/18
|
11.8%
2/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Buttock pain
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Muscle cramp
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/20
|
11.1%
2/18
|
0.00%
0/17
|
0.00%
0/33
|
11.1%
3/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
16.7%
1/6
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/20
|
5.6%
1/18
|
11.8%
2/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
28.6%
2/7
|
28.6%
2/7
|
16.7%
1/6
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.0%
2/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Nodule on extremity
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.0%
2/20
|
5.6%
1/18
|
5.9%
1/17
|
9.1%
3/33
|
0.00%
0/27
|
11.1%
1/9
|
28.6%
2/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
5.0%
1/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Tendon disorder
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign lung neoplasm
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Central nervous system leukaemia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia cutis
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Amnesia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
6.1%
2/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Ataxia
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Brain mass
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Disturbance in attention
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Dizziness
|
10.0%
2/20
|
11.1%
2/18
|
5.9%
1/17
|
6.1%
2/33
|
25.9%
7/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
33.3%
2/6
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Nervous system disorders
Headache
|
35.0%
7/20
|
27.8%
5/18
|
11.8%
2/17
|
12.1%
4/33
|
18.5%
5/27
|
33.3%
3/9
|
42.9%
3/7
|
42.9%
3/7
|
33.3%
2/6
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Hypogeusia
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Lethargy
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Neurological symptom
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Peroneal nerve palsy
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Postictal state
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Sinus headache
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Nervous system disorders
Sleep apnoea syndrome
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Somnolence
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Tremor
|
10.0%
2/20
|
0.00%
0/18
|
0.00%
0/17
|
6.1%
2/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Psychiatric disorders
Agitation
|
5.0%
1/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Psychiatric disorders
Anxiety
|
20.0%
4/20
|
16.7%
3/18
|
5.9%
1/17
|
9.1%
3/33
|
11.1%
3/27
|
11.1%
1/9
|
0.00%
0/7
|
14.3%
1/7
|
16.7%
1/6
|
|
Psychiatric disorders
Confusional state
|
10.0%
2/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Psychiatric disorders
Depression
|
10.0%
2/20
|
5.6%
1/18
|
0.00%
0/17
|
6.1%
2/33
|
11.1%
3/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Psychiatric disorders
Hallucination NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Psychiatric disorders
Insomnia
|
10.0%
2/20
|
5.6%
1/18
|
11.8%
2/17
|
9.1%
3/33
|
14.8%
4/27
|
22.2%
2/9
|
28.6%
2/7
|
0.00%
0/7
|
50.0%
3/6
|
|
Psychiatric disorders
Restlessness
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Renal and urinary disorders
Bladder pain
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/20
|
5.6%
1/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Renal and urinary disorders
Urge incontinence
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Breath sounds decreased
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
35.0%
7/20
|
22.2%
4/18
|
23.5%
4/17
|
18.2%
6/33
|
11.1%
3/27
|
22.2%
2/9
|
0.00%
0/7
|
14.3%
1/7
|
33.3%
2/6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.0%
3/20
|
27.8%
5/18
|
11.8%
2/17
|
24.2%
8/33
|
29.6%
8/27
|
22.2%
2/9
|
42.9%
3/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
5.0%
1/20
|
5.6%
1/18
|
0.00%
0/17
|
12.1%
4/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.0%
2/20
|
11.1%
2/18
|
0.00%
0/17
|
3.0%
1/33
|
14.8%
4/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
5.0%
1/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Increased upper airway secretion
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
3.7%
1/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Nasal dryness
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
5.0%
1/20
|
5.6%
1/18
|
0.00%
0/17
|
12.1%
4/33
|
7.4%
2/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.0%
1/20
|
0.00%
0/18
|
17.6%
3/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
5.0%
1/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
5.0%
1/20
|
0.00%
0/18
|
5.9%
1/17
|
6.1%
2/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Rhonchi
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
0.00%
0/20
|
5.6%
1/18
|
5.9%
1/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Tonsillar ulcer
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
5.0%
1/20
|
0.00%
0/18
|
5.9%
1/17
|
3.0%
1/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Blood blister
|
0.00%
0/20
|
11.1%
2/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Contusion
|
10.0%
2/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
15.0%
3/20
|
11.1%
2/18
|
5.9%
1/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
28.6%
2/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Erythema
|
15.0%
3/20
|
0.00%
0/18
|
5.9%
1/17
|
6.1%
2/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
6.1%
2/33
|
3.7%
1/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
10.0%
2/20
|
5.6%
1/18
|
5.9%
1/17
|
9.1%
3/33
|
7.4%
2/27
|
11.1%
1/9
|
0.00%
0/7
|
42.9%
3/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Penile ulceration
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/20
|
22.2%
4/18
|
5.9%
1/17
|
6.1%
2/33
|
7.4%
2/27
|
11.1%
1/9
|
0.00%
0/7
|
14.3%
1/7
|
33.3%
2/6
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Purpura NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/20
|
5.6%
1/18
|
5.9%
1/17
|
3.0%
1/33
|
18.5%
5/27
|
22.2%
2/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
5.0%
1/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
14.3%
1/7
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/20
|
5.6%
1/18
|
5.9%
1/17
|
0.00%
0/33
|
3.7%
1/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Skin lesion NOS
|
5.0%
1/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
Subcutaneous nodule
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Urticaria NOS
|
10.0%
2/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Surgical and medical procedures
Sinus operation
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Haematoma
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
9.1%
3/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
14.3%
1/7
|
16.7%
1/6
|
|
Vascular disorders
Haematoma NOS
|
15.0%
3/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Hot flush
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Hypertension
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
3.0%
1/33
|
7.4%
2/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
33.3%
2/6
|
|
Vascular disorders
Hypotension
|
0.00%
0/20
|
11.1%
2/18
|
17.6%
3/17
|
6.1%
2/33
|
3.7%
1/27
|
11.1%
1/9
|
28.6%
2/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Hypotension NOS
|
10.0%
2/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Jugular vein thrombosis
|
0.00%
0/20
|
0.00%
0/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Pallor
|
0.00%
0/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
14.3%
1/7
|
14.3%
1/7
|
0.00%
0/6
|
|
Vascular disorders
Petechiae
|
15.0%
3/20
|
0.00%
0/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Phlebitis
|
0.00%
0/20
|
0.00%
0/18
|
11.8%
2/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/20
|
5.6%
1/18
|
5.9%
1/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
|
Vascular disorders
Wound haemorrhage
|
0.00%
0/20
|
5.6%
1/18
|
0.00%
0/17
|
0.00%
0/33
|
0.00%
0/27
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/7
|
0.00%
0/6
|
Additional Information
Study Director
Novartis
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER