Trial Outcomes & Findings for Safety, Tolerability, Efficacy and Pharmacokinetics of Copanlisib in Pediatric Patients (NCT NCT03458728)
NCT ID: NCT03458728
Last Updated: 2023-12-04
Results Overview
ORR was defined separately in each indication, as the number of responders divided by the number of subjects in FAS in the indication.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
31 participants
Primary outcome timeframe
Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Results posted on
2023-12-04
Participant Flow
The study was conducted at 14 centers in United States between 30 APR 2018 (First participant first visit) and 1-Feb-2023 (Last participant last visit).
41 participants were screened into the study (signed informed consent form (ICF)). 10 participants were screening failed. 31 participants were enrolled in the study, all 31 participants received treatment in phase 1 as the study was terminated prior to the initiation of the phase 2.
Participant milestones
| Measure |
Copanlisib 28mg/m*2, Total
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol. Copanlisib 28mg/m\*2 (Total) included AMD0 (5 participants who were under the original DLT criteria) and AMD1+ (19 participants who were under the amended DLT criteria).
|
Copanlisib 35mg/m*2
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
|---|---|---|
|
Overall Study
STARTED
|
24
|
7
|
|
Overall Study
Started Treatment
|
24
|
7
|
|
Overall Study
Terminated Treatment
|
24
|
7
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
24
|
7
|
Reasons for withdrawal
| Measure |
Copanlisib 28mg/m*2, Total
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol. Copanlisib 28mg/m\*2 (Total) included AMD0 (5 participants who were under the original DLT criteria) and AMD1+ (19 participants who were under the amended DLT criteria).
|
Copanlisib 35mg/m*2
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Progressive disease - clinical assessment
|
1
|
0
|
|
Overall Study
Progressive disease - radiological progression
|
21
|
6
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Safety, Tolerability, Efficacy and Pharmacokinetics of Copanlisib in Pediatric Patients
Baseline characteristics by cohort
| Measure |
Copanlisib 28mg/m*2, Total
n=24 Participants
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol. Copanlisib 28mg/m\*2 (Total) included AMD0 (5 participants who were under the original DLT criteria) and AMD1+ (19 participants who were under the amended DLT criteria).
|
Copanlisib 35mg/m*2
n=7 Participants
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
Total
n=31 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
12.5 years
STANDARD_DEVIATION 4.6 • n=5 Participants
|
12.3 years
STANDARD_DEVIATION 3.8 • n=7 Participants
|
12.5 years
STANDARD_DEVIATION 4.3 • n=5 Participants
|
|
Age, Customized
In utero
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Customized
Preterm newborn infants (gestational age < 37 wks)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Customized
Newborns (0-27 days)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Customized
Infants and toddlers (28 days-23 months)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Customized
Children (2-11 years)
|
11 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Age, Customized
Adolescents (12-17 years)
|
10 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Age, Customized
Adults (18-64 years)
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Customized
From 65-84 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Customized
85 years and over
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
18 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (28 days)Population: Safety analysis set (SAF): The SAF population was defined as all participants with at least one intake of study drug.
Maximum tolerated dose (MTD) for copanlisib was defined as the highest dose level where 6 patients have been treated and ≤ 1 participant experienced a DLT. This endpoint was performed on SAF.
Outcome measures
| Measure |
Copanlisib_Phase 1
n=31 Participants
Copanlisib was administered on Day 1, Day 8, and Day 15 of every 28-day cycle. Subjects received copanlisib IV infusion with intermittent (3 weeks on / 1 week off) dosing schedule at the assigned dose level.
|
Copanlisib 35mg/m*2
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
|---|---|---|
|
Phase 1: The Maximum Tolerated Dose (MTD): the Highest Dose Level of Copanlisib That Can be Given so That Not More Than 1 Out of 6 Patients Experience a DLT During the DLT Evaluation Period.
|
28 mg/m*2/dose
|
—
|
PRIMARY outcome
Timeframe: Cycle 1 (28 days)Population: Safety analysis set (SAF): The SAF population was defined as all participants with at least one intake of study drug.
DLT was observed during first cycle of treatment, and assessed as possibly, probably or definitely related to treatment with copanlisib. The DLT observation period for the purposes of dose-escalation was the first cycle of therapy.
Outcome measures
| Measure |
Copanlisib_Phase 1
n=24 Participants
Copanlisib was administered on Day 1, Day 8, and Day 15 of every 28-day cycle. Subjects received copanlisib IV infusion with intermittent (3 weeks on / 1 week off) dosing schedule at the assigned dose level.
|
Copanlisib 35mg/m*2
n=7 Participants
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
|---|---|---|
|
Phase 1: Number of Subjects With Dose Limiting Toxicity (DLT)
|
3 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 145 days.Population: Safety analysis set (SAF): The SAF population was defined as all participants with at least one intake of study drug.
TEAE was defined as any event arising or worsening after start of study drug administration until 30 days after the last dose of the study drug intake (end of safety follow-up). This endpoint was performed on SAF.
Outcome measures
| Measure |
Copanlisib_Phase 1
n=24 Participants
Copanlisib was administered on Day 1, Day 8, and Day 15 of every 28-day cycle. Subjects received copanlisib IV infusion with intermittent (3 weeks on / 1 week off) dosing schedule at the assigned dose level.
|
Copanlisib 35mg/m*2
n=7 Participants
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
|---|---|---|
|
Phase 1: Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
|
24 Participants
|
7 Participants
|
PRIMARY outcome
Timeframe: Up to 150 days.Population: Safety analysis set (SAF): The SAF population was defined as all participants with at least one intake of study drug.
This endpoint was performed on SAF.
Outcome measures
| Measure |
Copanlisib_Phase 1
n=24 Participants
Copanlisib was administered on Day 1, Day 8, and Day 15 of every 28-day cycle. Subjects received copanlisib IV infusion with intermittent (3 weeks on / 1 week off) dosing schedule at the assigned dose level.
|
Copanlisib 35mg/m*2
n=7 Participants
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
|---|---|---|
|
Phase 1: Number of Subjects With Serious Adverse Events (SAEs)
|
10 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 145 days.Population: Safety analysis set (SAF): The SAF population was defined as all participants with at least one intake of study drug.
This endpoint was performed on SAF.
Outcome measures
| Measure |
Copanlisib_Phase 1
n=24 Participants
Copanlisib was administered on Day 1, Day 8, and Day 15 of every 28-day cycle. Subjects received copanlisib IV infusion with intermittent (3 weeks on / 1 week off) dosing schedule at the assigned dose level.
|
Copanlisib 35mg/m*2
n=7 Participants
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
|---|---|---|
|
Phase 1: Number of Participants With Treatment-related Adverse Events (AEs).
|
5 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.Population: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
ORR was defined separately in each indication, as the number of responders divided by the number of subjects in FAS in the indication.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.Population: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
The DCR was defined as the number of subjects with disease control divided by the number of subjects in FAS or per protocol set (PPS) in the indication.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.Population: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Age ≥ 6 years: Pre-dose, Post-dose on Cycle 1 Day 1 and Day 15 (1-1.25 hour (h), 1.5- 3h, 22-24h). Age < 6 years: Pre-dose, Post-dose on Cycle 1 Day 1 and Day 15 (1-1.25h, 22-24h). Cycle length is 28 days.Population: For all participants included in the PK analysis set, copanlisib PK was analyzed using an established comprehensive population PK model with incorporation of allometric scaling by Body surface area (BSA) on copanlisib disposition parameters (clearance and volume parameters). The model with allometric scaling enables combining of treatment groups and was used to estimate copanlisib PK parameters (AUC0-168h and Cmax).
Cmax: maximum concentration after the 3rd dose in a sequence of 3 nominal doses of copanlisib. PK analysis set: All participants with at least one intake of study drug and with at least one valid measurement for copanlisib were included in the copanlisib PK analysis.
Outcome measures
| Measure |
Copanlisib_Phase 1
n=30 Participants
Copanlisib was administered on Day 1, Day 8, and Day 15 of every 28-day cycle. Subjects received copanlisib IV infusion with intermittent (3 weeks on / 1 week off) dosing schedule at the assigned dose level.
|
Copanlisib 35mg/m*2
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
|---|---|---|
|
Phase 1: Copanlisib Maximum Drug Concentration (Cmax)
|
359 μg/L
Geometric Coefficient of Variation 22.6
|
—
|
SECONDARY outcome
Timeframe: Age ≥ 6 years: Pre-dose, Post-dose on Cycle 1 Day 1 and Day 15 (1-1.25 hour (h), 1.5- 3h, 22-24h). Age < 6 years: Pre-dose, Post-dose on Cycle 1 Day 1 and Day 15 (1-1.25h, 22-24h). Cycle length is 28 days.Population: For all participants included in the PK analysis set, copanlisib PK was analyzed using an established comprehensive population PK model with incorporation of allometric scaling by Body surface area (BSA) on copanlisib disposition parameters (clearance and volume parameters). The model with allometric scaling enables combining of treatment groups and was used to estimate copanlisib PK parameters (AUC0-168h and Cmax).
AUC(0-168): Area under the concentration-time curve \[AUC\] from 0 to 168 hours after the 3rd dose in a sequence of 3 nominal doses of copanlisib. PK analysis set: All participants with at least one intake of study drug and with at least one valid measurement for copanlisib were included in the copanlisib PK analysis.
Outcome measures
| Measure |
Copanlisib_Phase 1
n=30 Participants
Copanlisib was administered on Day 1, Day 8, and Day 15 of every 28-day cycle. Subjects received copanlisib IV infusion with intermittent (3 weeks on / 1 week off) dosing schedule at the assigned dose level.
|
Copanlisib 35mg/m*2
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
|---|---|---|
|
Phase 1: Area Under the Curve (AUC(0-168))
|
2900 μg∙h/L
Geometric Coefficient of Variation 35.4
|
—
|
SECONDARY outcome
Timeframe: Up to 150 daysPopulation: Full analysis set (FAS): All subjects with at least one intake of study drug.
ORR by dose cohort is defined as the number of responders divided by the number of subjects in FAS in the indication. The analysis of ORR was performed on FAS.
Outcome measures
| Measure |
Copanlisib_Phase 1
n=24 Participants
Copanlisib was administered on Day 1, Day 8, and Day 15 of every 28-day cycle. Subjects received copanlisib IV infusion with intermittent (3 weeks on / 1 week off) dosing schedule at the assigned dose level.
|
Copanlisib 35mg/m*2
n=7 Participants
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
|---|---|---|
|
Phase 1: Objective Response Rate (ORR)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.Population: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.Population: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.Population: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.Population: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.Population: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.Population: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Outcome measures
Outcome data not reported
Adverse Events
Copanlisib 28mg/m*2, Total
Serious events: 10 serious events
Other events: 23 other events
Deaths: 20 deaths
Copanlisib 35mg/m*2
Serious events: 0 serious events
Other events: 7 other events
Deaths: 5 deaths
Serious adverse events
| Measure |
Copanlisib 28mg/m*2, Total
n=24 participants at risk
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol. Copanlisib 28mg/m\*2 (Total) included AMD0 (5 participants who were under the original DLT criteria) and AMD1+ (19 participants who were under the amended DLT criteria).
|
Copanlisib 35mg/m*2
n=7 participants at risk
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease,unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
4.2%
1/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Cardiac disorders
Pericardial effusion
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Cardiac disorders
Sinus bradycardia
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Gastrointestinal disorders
Abdominal pain
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
General disorders
Pyrexia
|
20.8%
5/24 • Number of events 5 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
General disorders
Non-cardiac chest pain
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Blood creatinine increased
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Neutrophil count decreased
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
White blood cell count decreased
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Dehydration
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
12.5%
3/24 • Number of events 8 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
4.2%
1/24 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Nervous system disorders
Spinal cord compression
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
Other adverse events
| Measure |
Copanlisib 28mg/m*2, Total
n=24 participants at risk
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol. Copanlisib 28mg/m\*2 (Total) included AMD0 (5 participants who were under the original DLT criteria) and AMD1+ (19 participants who were under the amended DLT criteria).
|
Copanlisib 35mg/m*2
n=7 participants at risk
Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease,unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
54.2%
13/24 • Number of events 38 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
42.9%
3/7 • Number of events 8 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
29.2%
7/24 • Number of events 21 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
42.9%
3/7 • Number of events 4 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Cardiac disorders
Pericardial effusion
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Cardiac disorders
Sinus bradycardia
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Cardiac disorders
Sinus tachycardia
|
25.0%
6/24 • Number of events 7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
42.9%
3/7 • Number of events 4 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Eye disorders
Dry eye
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Eye disorders
Vision blurred
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Gastrointestinal disorders
Abdominal distension
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Gastrointestinal disorders
Abdominal pain
|
20.8%
5/24 • Number of events 9 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Gastrointestinal disorders
Constipation
|
16.7%
4/24 • Number of events 6 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
57.1%
4/7 • Number of events 4 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
8/24 • Number of events 8 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Gastrointestinal disorders
Nausea
|
62.5%
15/24 • Number of events 22 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
57.1%
4/7 • Number of events 7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Gastrointestinal disorders
Stomatitis
|
8.3%
2/24 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Gastrointestinal disorders
Vomiting
|
29.2%
7/24 • Number of events 11 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
57.1%
4/7 • Number of events 12 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
General disorders
Fatigue
|
41.7%
10/24 • Number of events 14 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
42.9%
3/7 • Number of events 7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
General disorders
Gait disturbance
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
General disorders
Oedema peripheral
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
General disorders
Pain
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
General disorders
Pyrexia
|
33.3%
8/24 • Number of events 19 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
57.1%
4/7 • Number of events 7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
General disorders
Non-cardiac chest pain
|
16.7%
4/24 • Number of events 5 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Activated partial thromboplastin time prolonged
|
25.0%
6/24 • Number of events 6 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Alanine aminotransferase increased
|
25.0%
6/24 • Number of events 8 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Amylase increased
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Aspartate aminotransferase increased
|
25.0%
6/24 • Number of events 11 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Blood cholesterol increased
|
20.8%
5/24 • Number of events 5 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Blood creatinine increased
|
16.7%
4/24 • Number of events 4 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 4 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Blood lactate dehydrogenase increased
|
20.8%
5/24 • Number of events 6 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
C-reactive protein increased
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Carbon dioxide decreased
|
12.5%
3/24 • Number of events 8 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
High density lipoprotein decreased
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
International normalised ratio increased
|
12.5%
3/24 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Lipase increased
|
20.8%
5/24 • Number of events 7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Lymphocyte count decreased
|
54.2%
13/24 • Number of events 35 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
42.9%
3/7 • Number of events 7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Neutrophil count decreased
|
25.0%
6/24 • Number of events 14 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 9 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Neutrophil count increased
|
8.3%
2/24 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Protein total decreased
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Weight decreased
|
12.5%
3/24 • Number of events 6 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
White blood cell count decreased
|
50.0%
12/24 • Number of events 21 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
71.4%
5/7 • Number of events 7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Investigations
Blood alkaline phosphatase increased
|
16.7%
4/24 • Number of events 4 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
70.8%
17/24 • Number of events 44 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
57.1%
4/7 • Number of events 8 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
16.7%
4/24 • Number of events 5 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
25.0%
6/24 • Number of events 7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
12.5%
3/24 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
41.7%
10/24 • Number of events 16 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
33.3%
8/24 • Number of events 12 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
12.5%
3/24 • Number of events 10 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
16.7%
4/24 • Number of events 8 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
45.8%
11/24 • Number of events 16 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
29.2%
7/24 • Number of events 11 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Hypouricaemia
|
8.3%
2/24 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
25.0%
6/24 • Number of events 8 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 4 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
25.0%
6/24 • Number of events 7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
29.2%
7/24 • Number of events 12 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
33.3%
8/24 • Number of events 12 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Nervous system disorders
Dizziness
|
12.5%
3/24 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Nervous system disorders
Headache
|
37.5%
9/24 • Number of events 11 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Nervous system disorders
Somnolence
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Nervous system disorders
Tremor
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Psychiatric disorders
Agitation
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Psychiatric disorders
Anxiety
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Psychiatric disorders
Depression
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Psychiatric disorders
Hallucination
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Psychiatric disorders
Insomnia
|
12.5%
3/24 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Psychiatric disorders
Irritability
|
8.3%
2/24 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Renal and urinary disorders
Haematuria
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
6/24 • Number of events 7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.8%
5/24 • Number of events 7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
12.5%
3/24 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
12.5%
3/24 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
12.5%
3/24 • Number of events 3 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
12.5%
3/24 • Number of events 4 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
8.3%
2/24 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
0.00%
0/7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/24 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
4.2%
1/24 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 1 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Vascular disorders
Hypertension
|
41.7%
10/24 • Number of events 42 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
28.6%
2/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
|
Vascular disorders
Hypotension
|
29.2%
7/24 • Number of events 7 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
14.3%
1/7 • Number of events 2 • After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 150 days. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with a maximum of 150 days.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER