Trial Outcomes & Findings for GANNET53: Ganetespib in Metastatic, p53-mutant, Platinum-resistant Ovarian Cancer (NCT NCT02012192)

NCT ID: NCT02012192

Last Updated: 2019-08-13

Results Overview

evaluate the efficacy of ganetespib in combination with weekly paclitaxel compared to weekly paclitaxel alone as measured by Progression-free survival (PFS). Response or progression will be evaluated in this study according to Response Evaluation Criteria In Solid Tumors Criteria version 1.1., CA-125 according to published GCIG criteria, and by the investigator on the basis of physical and/or gynaecological examinations.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

133 participants

Primary outcome timeframe

Time until progression (median w/o new drug 4 months)

Results posted on

2019-08-13

Participant Flow

Participant milestones

Participant milestones
Measure	Ganetespib + Paclitaxel Drug: ganetespib, 150 mg/m², given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle); Drug: paclitaxel, 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression. Ganetespib Paclitaxel	Paclitaxel Drug: paclitaxel: 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression Paclitaxel
Overall Study STARTED	90	43
Overall Study COMPLETED	63	43
Overall Study NOT COMPLETED	27	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

GANNET53: Ganetespib in Metastatic, p53-mutant, Platinum-resistant Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ganetespib + Paclitaxel n=90 Participants Drug: ganetespib, 150 mg/m², given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle); Drug: paclitaxel, 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression.	Paclitaxel n=43 Participants Drug: paclitaxel: 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression	Total n=133 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	57 Participants n=5 Participants	25 Participants n=7 Participants	82 Participants n=5 Participants
Age, Categorical >=65 years	33 Participants n=5 Participants	18 Participants n=7 Participants	51 Participants n=5 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	43 Participants n=7 Participants	133 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Ethnic group · White	66 Participants n=5 Participants	31 Participants n=7 Participants	97 Participants n=5 Participants
Race/Ethnicity, Customized Ethnic group · Black	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Ethnic group · Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Ethnic group · Privacy	23 Participants n=5 Participants	12 Participants n=7 Participants	35 Participants n=5 Participants
Region of Enrollment Austria	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Belgium	20 participants n=5 Participants	10 participants n=7 Participants	30 participants n=5 Participants
Region of Enrollment France	37 participants n=5 Participants	17 participants n=7 Participants	54 participants n=5 Participants
Region of Enrollment Germany	32 participants n=5 Participants	15 participants n=7 Participants	47 participants n=5 Participants

PRIMARY outcome

Timeframe: Time until progression (median w/o new drug 4 months)

Population: ITT population

Outcome measures

Outcome measures
Measure	Ganetespib + Paclitaxel n=90 Participants Drug: ganetespib, 150 mg/m², given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle); Drug: paclitaxel, 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression.	Paclitaxel n=43 Participants Drug: paclitaxel: 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression
Progression Free Survival (PFS)	3.5 months Interval 3.092 to 3.882	5.3 months Interval 4.006 to 6.652

Adverse Events

Ganetespib + Paclitaxel

Serious events: 34 serious events

Other events: 88 other events

Deaths: 66 deaths

Paclitaxel

Serious events: 10 serious events

Other events: 41 other events

Deaths: 29 deaths

Serious adverse events

Other adverse events

Additional Information

Prof. Dr. Nicole Concin

Medical University of Innsbruck

Phone: +43 512 504

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Ganetespib + Paclitaxel n=90 participants at risk Drug: ganetespib, 150 mg/m², given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle); Drug: paclitaxel, 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression.	Paclitaxel n=43 participants at risk Drug: paclitaxel: 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression
Blood and lymphatic system disorders Anemia	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Blood and lymphatic system disorders febrile neutropenia	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Blood and lymphatic system disorders Hypovolemia	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Abdominal distention	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Abdominal pain	3.3% 3/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	2.3% 1/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Anal hemorrhage	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	2.3% 1/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Diarrhea	3.3% 3/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Esophagitis	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Ileus	2.2% 2/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	2.3% 1/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Rectal Ulcer	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Small intestinal obstruction	8.9% 8/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	2.3% 1/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Small intestinal perforation	2.2% 2/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Subileus	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Subobstruction colon	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Vomiting	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	4.7% 2/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
General disorders Fever	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	2.3% 1/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
General disorders General physical health deterioration	2.2% 2/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	2.3% 1/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
General disorders Infusion site extravasation	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	2.3% 1/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
General disorders Sudden death NOS	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Hepatobiliary disorders Hemobilia	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Hepatobiliary disorders Hepatic failure	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Hepatobiliary disorders Icterus	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Infections and infestations Sepsis	6.7% 6/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Infections and infestations Urinary tract infection	5.6% 5/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	2.3% 1/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Infections and infestations Erysipelas	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	7.0% 3/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Infections and infestations Catheter related infection	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Infections and infestations Urethral infection	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Infections and infestations Infection NOS	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	2.3% 1/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Injury, poisoning and procedural complications Rupture of renal pelvis	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Injury, poisoning and procedural complications Vascular access complication	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	2.3% 1/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Metabolism and nutrition disorders Anorexia	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Metabolism and nutrition disorders Hyperptassemia	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Metabolism and nutrition disorders Hypokalemia	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Nervous system disorders Visual acuity reduced	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Renal and urinary disorders Acute kidney injury	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Renal and urinary disorders Cystitis	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Renal and urinary disorders Kidney insufficiency	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Renal and urinary disorders Renal disorders NEC	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	4.7% 2/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.1% 1/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.

Other adverse events
Measure	Ganetespib + Paclitaxel n=90 participants at risk Drug: ganetespib, 150 mg/m², given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle); Drug: paclitaxel, 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression.	Paclitaxel n=43 participants at risk Drug: paclitaxel: 80 mg/m2, given iv once weekly for 3 out of 4 weeks (days 1, 8, 15 of each 4-weeks/28-days cycle), until progression
Blood and lymphatic system disorders Anemia	62.2% 56/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	62.8% 27/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Abdominal pain	34.4% 31/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	27.9% 12/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Blood and lymphatic system disorders Thrombocytopenia	7.8% 7/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Abdominal distention	8.9% 8/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	4.7% 2/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Constipation	23.3% 21/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	20.9% 9/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Diarrhea	81.1% 73/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	34.9% 15/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Dry mouth	6.7% 6/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	4.7% 2/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Dyspepsia	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	7.0% 3/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Gastroesophageal reflux disease	6.7% 6/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	4.7% 2/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Mucositis oral	5.6% 5/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Nausea	45.6% 41/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	48.8% 21/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Gastrointestinal disorders Vomiting	32.2% 29/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	20.9% 9/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
General disorders Astenia	24.4% 22/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	25.6% 11/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
General disorders Edema limbs	7.8% 7/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	9.3% 4/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
General disorders Edema peripheral	6.7% 6/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	16.3% 7/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
General disorders Fatigue	28.9% 26/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	18.6% 8/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
General disorders Fever	11.1% 10/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
General disorders Malaise	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	7.0% 3/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
General disorders Mucosal inflammation	5.6% 5/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Immune system disorders Allergic reaction	5.6% 5/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	7.0% 3/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Infections and infestations Bronchial infection	5.6% 5/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Infections and infestations Urinary tract infection	8.9% 8/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	14.0% 6/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Investigations Alanine aminotransferase increased	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	4.7% 2/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Investigations Aspartate aminotransferase increased	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	7.0% 3/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Investigations Electrocardiogram QT corrected intervall prolonged	14.4% 13/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Investigations Lymphocyte count decreased	10.0% 9/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	9.3% 4/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Investigations Neutrophil count decreased	28.9% 26/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	23.3% 10/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Investigations Weight loss	10.0% 9/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	0.00% 0/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Investigations White blood cells decreased	14.4% 13/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	14.0% 6/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Metabolism and nutrition disorders Anorexia	20.0% 18/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	14.0% 6/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Metabolism and nutrition disorders Hypokalaemia	7.8% 7/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	7.0% 3/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Musculoskeletal and connective tissue disorders Anthralgia	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	4.7% 2/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Musculoskeletal and connective tissue disorders Back pain	10.0% 9/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	9.3% 4/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Musculoskeletal and connective tissue disorders Muscle spasms	12.2% 11/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	4.7% 2/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	7.0% 3/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 9/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	7.0% 3/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Nervous system disorders Dizziness	0.00% 0/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	4.7% 2/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Nervous system disorders Dysgeusia	5.6% 5/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	11.6% 5/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Nervous system disorders Headache	11.1% 10/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	4.7% 2/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.
Nervous system disorders Neuropath peripheral	38.9% 35/90 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.	48.8% 21/43 • After informed consent has been obtained but prior to initiation of the study drug, only SAEs considered to be related to a protocol-mandated intervention were reported. After initiation of study drug, all AEs and SAEs regardless of relationship to the study drug, will be reported until safety follow-up at 28 days after the last dose of IMP or EOT or until the event has resolved to baseline grade or better. An AE is any untoward adverse change from the subject's baseline condition, i.e. any unfavourable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician that occurs during the course of the study, whether or not considered related to the study drug. All AEs collected during the course of the trial (from the time of informed consent until EOT as described above) have been reported here.