Trial Outcomes & Findings for Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension in Subjects at High Risk for Invasive Fungal Infections (P05520) (NCT NCT01075984)
NCT ID: NCT01075984
Last Updated: 2017-11-13
Results Overview
Blood samples were collected from participants for the determination of plasma POS concentration.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
279 participants
Primary outcome timeframe
12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)
Results posted on
2017-11-13
Participant Flow
All participants who started the study were eligible to enter the follow-up phase, whether or not they completed the treatment phase.
Participant milestones
| Measure |
Posaconazole (POS) 200 mg IV Single Dose (Cohort 0)
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
Placebo IV Single Dose (Cohort 0)
Placebo IV single dose on Day 1, followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
POS 300 mg IV BID (Cohort 2)
POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 300 mg IV BID (Cohort 3)
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
|---|---|---|---|---|---|
|
Treatment Phase
STARTED
|
10
|
11
|
21
|
24
|
213
|
|
Treatment Phase
COMPLETED
|
10
|
10
|
14
|
17
|
153
|
|
Treatment Phase
NOT COMPLETED
|
0
|
1
|
7
|
7
|
60
|
|
Follow-up Phase
STARTED
|
10
|
10
|
20
|
21
|
212
|
|
Follow-up Phase
COMPLETED
|
10
|
10
|
19
|
19
|
165
|
|
Follow-up Phase
NOT COMPLETED
|
0
|
0
|
1
|
2
|
47
|
Reasons for withdrawal
| Measure |
Posaconazole (POS) 200 mg IV Single Dose (Cohort 0)
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
Placebo IV Single Dose (Cohort 0)
Placebo IV single dose on Day 1, followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
POS 300 mg IV BID (Cohort 2)
POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 300 mg IV BID (Cohort 3)
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
|---|---|---|---|---|---|
|
Treatment Phase
Adverse Event
|
0
|
1
|
3
|
7
|
35
|
|
Treatment Phase
Protocol Violation
|
0
|
0
|
1
|
0
|
3
|
|
Treatment Phase
Withdrawal by Subject
|
0
|
0
|
2
|
0
|
15
|
|
Treatment Phase
Treatment Failure
|
0
|
0
|
1
|
0
|
5
|
|
Treatment Phase
Progression of disease
|
0
|
0
|
0
|
0
|
2
|
|
Follow-up Phase
Protocol Violation
|
0
|
0
|
1
|
0
|
3
|
|
Follow-up Phase
Adverse Event
|
0
|
0
|
0
|
2
|
27
|
|
Follow-up Phase
Administrative
|
0
|
0
|
0
|
0
|
1
|
|
Follow-up Phase
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
10
|
|
Follow-up Phase
Progression of disease
|
0
|
0
|
0
|
0
|
2
|
|
Follow-up Phase
Treatment failure
|
0
|
0
|
0
|
0
|
4
|
Baseline Characteristics
Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension in Subjects at High Risk for Invasive Fungal Infections (P05520)
Baseline characteristics by cohort
| Measure |
POS 200 mg IV Single Dose (Cohort 0)
n=10 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
Placebo IV Single Dose (Cohort 0)
n=11 Participants
Placebo IV single dose on Day 1, followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=21 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
POS 300 mg IV BID (Cohort 2)
n=24 Participants
POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 300 mg IV BID (Cohort 3)
n=213 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
Total
n=279 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
56.8 Years
STANDARD_DEVIATION 17.4 • n=5 Participants
|
59.5 Years
STANDARD_DEVIATION 12.3 • n=7 Participants
|
49.1 Years
STANDARD_DEVIATION 14.7 • n=5 Participants
|
52.4 Years
STANDARD_DEVIATION 13.4 • n=4 Participants
|
50.7 Years
STANDARD_DEVIATION 14.7 • n=21 Participants
|
51.3 Years
STANDARD_DEVIATION 14.7 • n=8 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
96 Participants
n=21 Participants
|
126 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
117 Participants
n=21 Participants
|
153 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=22 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=10 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=20 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Single Dose Trough Concentration of IV Posaconazole (Cmin)
|
467 ng/mL
Standard Deviation 172
|
318 ng/mL
Standard Deviation 107
|
295 ng/mL
Standard Deviation 113
|
PRIMARY outcome
Timeframe: 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=30 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=15 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=19 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Steady State Trough Concentration of IV Posaconazole (Cmin)
|
1164 ng/mL
Standard Deviation 462
|
958 ng/mL
Standard Deviation 605
|
1046 ng/mL
Standard Deviation 515
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=22 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=10 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=20 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Single Dose Maximum Concentration of IV Posaconazole (Cmax)
|
1590 ng/mL
Standard Deviation 980
|
881 ng/mL
Standard Deviation 334
|
990 ng/mL
Standard Deviation 467
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=30 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=15 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=19 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Steady State Maximum Concentration of IV Posaconazole (Cmax)
|
3696 ng/mL
Standard Deviation 2950
|
1947 ng/mL
Standard Deviation 966
|
2610 ng/mL
Standard Deviation 1010
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0 and 1)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=22 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=10 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=20 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Single Dose Time of Observed Maximum Concentration of IV Posaconazole (Tmax)
|
1.54 Hours
Interval 1.0 to 1.92
|
1.42 Hours
Interval 0.95 to 1.78
|
1.48 Hours
Full Range 50 • Interval 1.0 to 3.97
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=30 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=15 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=19 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Steady State Time of Observed Maximum Concentration of IV Posaconazole (Tmax)
|
1.52 Hours
Full Range 80 • Interval 1.0 to 2.0
|
1.00 Hours
Full Range 50 • Interval 1.0 to 4.02
|
1.50 Hours
Full Range 39 • Interval 0.98 to 4.0
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=22 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=10 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=20 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Single Dose Area Under the Concentration Versus Time Curve of IV Posaconazole (AUC)
|
8240 hour*ng/mL
Standard Deviation 2140
|
5940 hour*ng/mL
Standard Deviation 2190
|
5390 hour*ng/mL
Standard Deviation 1540
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 1.75, 4, 8, 12, and 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=30 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=15 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=19 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Steady State Area Under the Concentration Versus Time Curve of IV Posaconazole (AUC)
|
37586 hour*ng/mL
Standard Deviation 11504
|
28241 hour*ng/mL
Standard Deviation 14511
|
33754 hour*ng/mL
Standard Deviation 14196
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 1.75, 4, 8, 12, and 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens.
Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (24 hours).
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=30 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=15 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=19 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Steady State Average Concentration of IV Posaconazole (Cavg)
|
1566 ng/mL
Standard Deviation 479
|
1180 ng/mL
Standard Deviation 605
|
1410 ng/mL
Standard Deviation 592
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)Population: CL for posaconazole was not calculated in this study because it was collected in other studies more appropriate for evaluation of this parameter.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=4 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=15 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=7 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Steady State Trough Concentration of Oral Posaconazole (Cmin)
|
316 ng/mL
Standard Deviation 164
|
370 ng/mL
Standard Deviation 125
|
532 ng/mL
Standard Deviation 266
|
PRIMARY outcome
Timeframe: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=4 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=15 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=7 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Steady State Maximum Concentration of Oral Posaconazole (Cmax)
|
430 ng/mL
Standard Deviation 260
|
494 ng/mL
Standard Deviation 176
|
811 ng/mL
Standard Deviation 208
|
PRIMARY outcome
Timeframe: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=4 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=15 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=7 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Steady State Time of Observed Maximum Concentration of Oral Posaconazole (Tmax)
|
5.54 Hours
Full Range 39 • Interval 2.97 to 11.62
|
3.03 Hours
Interval 2.73 to 5.13
|
3.05 Hours
Full Range 50 • Interval 0.0 to 8.13
|
PRIMARY outcome
Timeframe: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure.
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=4 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=15 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=7 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Steady State Area Under the Concentration Versus Time Curve of Oral Posaconazole (AUC)
|
3970 hour*ng/mL
Standard Deviation 2050
|
5080 hour*ng/mL
Standard Deviation 1700
|
6920 hour*ng/mL
Standard Deviation 1910
|
PRIMARY outcome
Timeframe: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)Population: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure.
Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (12 hours).
Outcome measures
| Measure |
POS 300 mg IV BID (Cohort 3)
n=4 Participants
POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
POS 200 mg IV Single Dose (Cohort 0)
n=15 Participants
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=7 Participants
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
|---|---|---|---|
|
Steady State Average Concentration of Oral Posaconazole (Cavg)
|
331 ng/mL
Standard Deviation 172
|
423 ng/mL
Standard Deviation 144
|
570 ng/mL
Standard Deviation 160
|
PRIMARY outcome
Timeframe: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)Population: CL/F for posaconazole was not calculated in this study because it was collected in other studies more appropriate for evaluation of this parameter
Blood samples were collected from participants for the determination of plasma POS concentration.
Outcome measures
Outcome data not reported
Adverse Events
POS 200 mg IV Single Dose (Cohort 0)
Serious events: 2 serious events
Other events: 10 other events
Deaths: 0 deaths
Placebo IV Single Dose (Cohort 0)
Serious events: 2 serious events
Other events: 11 other events
Deaths: 0 deaths
POS 200 mg IV BID (Cohort 1)
Serious events: 4 serious events
Other events: 20 other events
Deaths: 0 deaths
POS 300 mg IV BID (Cohort 2 and 3)
Serious events: 71 serious events
Other events: 229 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
POS 200 mg IV Single Dose (Cohort 0)
n=10 participants at risk
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
Placebo IV Single Dose (Cohort 0)
n=11 participants at risk
Placebo IV single dose on Day 1, followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=21 participants at risk
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
POS 300 mg IV BID (Cohort 2 and 3)
n=237 participants at risk
POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2); POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Agranulocytosis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Diarrhoea haemorrhagic
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Neutropenic colitis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Asthenia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Multi-organ failure
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Pyrexia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.1%
5/237 • Number of events 5 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Hepatobiliary disorders
Acute hepatic failure
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Immune system disorders
Graft versus host disease
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Immune system disorders
Graft versus host disease in intestine
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Immune system disorders
Graft versus host disease in lung
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Immune system disorders
Graft versus host disease in skin
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Aspergillosis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Bacterial sepsis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Cellulitis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Cytomegalovirus infection
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Enterococcal bacteraemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Escherichia sepsis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Meningoencephalitis bacterial
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Oral herpes
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Pneumonia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Pulmonary mycosis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Rotavirus infection
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Sepsis
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.1%
5/237 • Number of events 5 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Septic shock
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Injury, poisoning and procedural complications
Splenic rupture
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Injury, poisoning and procedural complications
Subdural haemorrhage
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Investigations
Smear cervix abnormal
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia recurrent
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Post transplant lymphoproliferative disorder
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
Headache
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
Myelitis transverse
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
Posterior reversible encephalopathy syndrome
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
VIIth nerve paralysis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 4 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Surgical and medical procedures
Tonsillectomy
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Vascular disorders
Hypotension
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Vascular disorders
Venoocclusive disease
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
Other adverse events
| Measure |
POS 200 mg IV Single Dose (Cohort 0)
n=10 participants at risk
POS 200 mg IV single dose on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
Placebo IV Single Dose (Cohort 0)
n=11 participants at risk
Placebo IV single dose on Day 1, followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
|
POS 200 mg IV BID (Cohort 1)
n=21 participants at risk
POS 200 mg IV BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
|
POS 300 mg IV BID (Cohort 2 and 3)
n=237 participants at risk
POS 300 mg IV BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2); POS 300 mg IV BID on Day 1 followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28 or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.3%
22/237 • Number of events 39 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
70.0%
7/10 • Number of events 9 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
45.5%
5/11 • Number of events 6 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
28.6%
6/21 • Number of events 8 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
21.9%
52/237 • Number of events 66 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.7%
4/237 • Number of events 7 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
10.1%
24/237 • Number of events 51 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Cardiac disorders
Atrial flutter
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
7.2%
17/237 • Number of events 18 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Ear and labyrinth disorders
Vertigo
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
6.3%
15/237 • Number of events 18 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Eye disorders
Dry eye
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
14.3%
3/21 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.9%
14/237 • Number of events 14 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Eye disorders
Eye haemorrhage
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Eye disorders
Ocular hyperaemia
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Eye disorders
Visual impairment
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
3.0%
7/237 • Number of events 7 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Abdominal pain
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
18.2%
2/11 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
14.3%
3/21 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
17.3%
41/237 • Number of events 46 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
30.0%
3/10 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
18.2%
2/11 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 4 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
10.5%
25/237 • Number of events 25 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Anal fistula
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Constipation
|
30.0%
3/10 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
12.7%
30/237 • Number of events 36 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
2/10 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
27.3%
3/11 • Number of events 5 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
28.6%
6/21 • Number of events 18 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
38.8%
92/237 • Number of events 131 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Dyspepsia
|
10.0%
1/10 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
7.2%
17/237 • Number of events 17 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Dysphagia
|
20.0%
2/10 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.1%
5/237 • Number of events 5 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Flatulence
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.5%
6/237 • Number of events 6 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
3.0%
7/237 • Number of events 8 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Gingival bleeding
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.2%
10/237 • Number of events 10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Haematochezia
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Haemorrhoids
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.5%
13/237 • Number of events 13 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Ileus paralytic
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
20.0%
2/10 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
3.8%
9/237 • Number of events 11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Nausea
|
20.0%
2/10 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
45.5%
5/11 • Number of events 5 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
42.9%
9/21 • Number of events 10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
28.3%
67/237 • Number of events 77 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Oedema mouth
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Oral disorder
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
6.3%
15/237 • Number of events 15 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Tongue coated
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.5%
6/237 • Number of events 7 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Tongue disorder
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Gastrointestinal disorders
Vomiting
|
30.0%
3/10 • Number of events 4 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
45.5%
5/11 • Number of events 6 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
17.7%
42/237 • Number of events 48 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Catheter site erythema
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
6.3%
15/237 • Number of events 18 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Catheter site haematoma
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Catheter site pain
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.9%
14/237 • Number of events 15 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Chills
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
16.0%
38/237 • Number of events 47 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Fatigue
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
10.1%
24/237 • Number of events 25 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Infusion site extravasation
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Injection site inflammation
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Mucosal inflammation
|
20.0%
2/10 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
18.6%
44/237 • Number of events 47 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Oedema
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
6.3%
15/237 • Number of events 16 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Oedema peripheral
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
27.3%
3/11 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
14.8%
35/237 • Number of events 39 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
General disorders
Pyrexia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
27.3%
3/11 • Number of events 4 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
28.6%
6/21 • Number of events 6 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
29.1%
69/237 • Number of events 96 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Hepatobiliary disorders
Cholestasis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
20.0%
2/10 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Atypical pneumonia
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
14.3%
3/21 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
3.0%
7/237 • Number of events 7 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Cellulitis
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Device related infection
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.5%
6/237 • Number of events 7 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Enterococcal infection
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
3.0%
7/237 • Number of events 7 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Infection
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Oral herpes
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
14.3%
3/21 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.9%
14/237 • Number of events 14 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Otitis media
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Pseudomonas infection
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Puncture site infection
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Sepsis
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.1%
5/237 • Number of events 5 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Staphylococcal bacteraemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
3.8%
9/237 • Number of events 10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Staphylococcal infection
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.5%
13/237 • Number of events 13 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Streptococcal bacteraemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Streptococcal infection
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Tonsillitis
|
10.0%
1/10 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Infections and infestations
Urinary tract infection
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
18.2%
2/11 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.7%
4/237 • Number of events 4 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.5%
6/237 • Number of events 6 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Investigations
Alanine aminotransferase increased
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.9%
14/237 • Number of events 14 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Investigations
Antithrombin III decreased
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Investigations
Blood creatinine increased
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.1%
12/237 • Number of events 12 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Investigations
Weight increased
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.1%
5/237 • Number of events 5 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
18.2%
2/11 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
12.2%
29/237 • Number of events 32 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Metabolism and nutrition disorders
Fluid retention
|
40.0%
4/10 • Number of events 4 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
3.0%
7/237 • Number of events 8 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.1%
12/237 • Number of events 12 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.1%
5/237 • Number of events 6 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
3.4%
8/237 • Number of events 8 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
30.0%
3/10 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
18.2%
2/11 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
14.3%
3/21 • Number of events 4 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
28.3%
67/237 • Number of events 77 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
12.7%
30/237 • Number of events 34 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.1%
5/237 • Number of events 9 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 5 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
8.9%
21/237 • Number of events 24 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.2%
10/237 • Number of events 10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.0%
2/10 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
7.2%
17/237 • Number of events 17 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
8.0%
19/237 • Number of events 21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.7%
4/237 • Number of events 4 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
20.0%
2/10 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
3.0%
7/237 • Number of events 7 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.2%
10/237 • Number of events 10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
Dizziness
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
6.8%
16/237 • Number of events 20 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
Dysgeusia
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.9%
14/237 • Number of events 14 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
Headache
|
40.0%
4/10 • Number of events 4 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
20.7%
49/237 • Number of events 53 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
27.3%
3/11 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
23.6%
56/237 • Number of events 71 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
10.0%
1/10 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Vascular disorders
Haematoma
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 4 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.1%
12/237 • Number of events 15 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Vascular disorders
Hypertension
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
11.0%
26/237 • Number of events 29 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Vascular disorders
Hypotension
|
20.0%
2/10 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
18.2%
2/11 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.9%
14/237 • Number of events 16 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Injury, poisoning and procedural complications
Allergic transfusion reaction
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
3.0%
7/237 • Number of events 7 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Nervous system disorders
Sensory loss
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.5%
13/237 • Number of events 14 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Psychiatric disorders
Confusional state
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
3.0%
7/237 • Number of events 8 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Psychiatric disorders
Hallucination
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.7%
4/237 • Number of events 4 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
14.3%
3/21 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
7.2%
17/237 • Number of events 18 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Psychiatric disorders
Nervousness
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.84%
2/237 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.5%
6/237 • Number of events 6 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
28.6%
6/21 • Number of events 6 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
13.1%
31/237 • Number of events 32 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
18.2%
2/11 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.7%
23/237 • Number of events 26 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
40.0%
4/10 • Number of events 4 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
16.9%
40/237 • Number of events 52 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
4.8%
1/21 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
7.2%
17/237 • Number of events 18 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal haemorrhage
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
1.3%
3/237 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/237 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.1%
1/11 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.42%
1/237 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Skin and subcutaneous tissue disorders
Erythema
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
5.5%
13/237 • Number of events 18 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
10.0%
1/10 • Number of events 1 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
2.1%
5/237 • Number of events 5 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
20.0%
2/10 • Number of events 3 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/21 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
10.1%
24/237 • Number of events 26 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/10 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
0.00%
0/11 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
9.5%
2/21 • Number of events 2 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
7.6%
18/237 • Number of events 20 • Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3)
|
Additional Information
Senior Vice President, Global Cllinical Development
Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator agrees not to publish or publicly present any interim results of the trial without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts.
- Publication restrictions are in place
Restriction type: OTHER