Trial Outcomes & Findings for NINLARO Capsules Drug Use-Results Survey (All-Case Surveillance) "Relapsed/Refractory Multiple Myeloma" (NCT NCT03169361)

Last Updated: 2023-12-07

Results Overview

An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Recruitment status

COMPLETED

Target enrollment

774 participants

Primary outcome timeframe

Up to 24 Week (From start of administration to the end of 6 cycles)

Results posted on

2023-12-07

Participant Flow

Participants took part in the survey at 316 investigative sites in Japan, from 24 May 2017 to 8 March 2022.

Participants with a historical diagnosis of relapsed/refractory multiple myeloma were enrolled. Participants received ixazomib as part of a routine medical care.

Participant milestones

Participant milestones
Measure	Ixazomib 4 mg The usual adult dosage for oral administration was 4 mg as ixazomib, in the fasting state, once a day, once a week for 3 weeks (Days 1, 8, and 15), with a 13-day washout period (Days 16 through 28). This 4-week cycle was repeated for 6 cycles. The dose might be reduced appropriately according to the patient's condition. Participants received interventions as part of routine medical care.
Overall Study STARTED	774
Overall Study COMPLETED	742
Overall Study NOT COMPLETED	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Ixazomib 4 mg The usual adult dosage for oral administration was 4 mg as ixazomib, in the fasting state, once a day, once a week for 3 weeks (Days 1, 8, and 15), with a 13-day washout period (Days 16 through 28). This 4-week cycle was repeated for 6 cycles. The dose might be reduced appropriately according to the patient's condition. Participants received interventions as part of routine medical care.
Overall Study Protocol Violation	32

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ixazomib 4 mg n=742 Participants The usual adult dosage for oral administration was 4 mg as ixazomib, in the fasting state, once a day, once a week for 3 weeks (Days 1, 8, and 15), with a 13-day washout period (Days 16 through 28). This 4-week cycle was repeated for 6 cycles. The dose might be reduced appropriately according to the patient's condition. Participants received interventions as part of routine medical care.
Age, Continuous	70.6 Years STANDARD_DEVIATION 9.85 • n=742 Participants
Sex: Female, Male Female	391 Participants n=742 Participants
Sex: Female, Male Male	351 Participants n=742 Participants
Region of Enrollment Japan	742 Participants n=742 Participants
Duration of Diagnosis of Relapsed/Refractory Multiple Myeloma	4.49 Years STANDARD_DEVIATION 3.902 • n=739 Participants • The number analyzed is the number of participants with data available for analysis.
Number of Participants with Relapsed/Refractory Multiple Myeloma	742 Participants n=742 Participants
International Staging System Stage I	140 Participants n=740 Participants • The number analyzed is the number of participants with data available for analysis.
International Staging System Stage II	260 Participants n=740 Participants • The number analyzed is the number of participants with data available for analysis.
International Staging System Stage III	290 Participants n=740 Participants • The number analyzed is the number of participants with data available for analysis.
International Staging System Missing	50 Participants n=740 Participants • The number analyzed is the number of participants with data available for analysis.
Eastern Cooperative Oncology Group Performance Status Scale = 0	240 Participants n=742 Participants
Eastern Cooperative Oncology Group Performance Status Scale = 1	294 Participants n=742 Participants
Eastern Cooperative Oncology Group Performance Status Scale = 2	112 Participants n=742 Participants
Eastern Cooperative Oncology Group Performance Status Scale = 3	81 Participants n=742 Participants
Eastern Cooperative Oncology Group Performance Status Scale = 4	15 Participants n=742 Participants
Healthcare Category Outpatient	436 Participants n=742 Participants
Healthcare Category Inpatient	306 Participants n=742 Participants
Hepatic Impairment Had No Hepatic Impairment	696 Participants n=742 Participants
Hepatic Impairment Had Hepatic Impairment	46 Participants n=742 Participants
Renal Impairment Had No Renal Impairment	448 Participants n=742 Participants
Renal Impairment Had Renal Impairment	294 Participants n=742 Participants
Medical Complications Had No Medical Complications	307 Participants n=741 Participants • The number analyzed is the number of participants with data available for analysis.
Medical Complications Had Medical Complications	434 Participants n=741 Participants • The number analyzed is the number of participants with data available for analysis.
Medical History Had No Medical History	475 Participants n=741 Participants • The number analyzed is the number of participants with data available for analysis.
Medical History Had Medical History	259 Participants n=741 Participants • The number analyzed is the number of participants with data available for analysis.
Medical History Unknown	7 Participants n=741 Participants • The number analyzed is the number of participants with data available for analysis.
Height	156.2 Centimeters (cm) STANDARD_DEVIATION 10.01 • n=715 Participants • The number analyzed is the number of participants with data available for analysis.
Weight	54.10 Kilograms (kg) STANDARD_DEVIATION 11.764 • n=709 Participants • The number analyzed is the number of participants with data available for analysis.
Body Surface Area	1.53 Square Meter STANDARD_DEVIATION 0.204 • n=705 Participants • The number analyzed is the number of participants with data available for analysis.

PRIMARY outcome

Timeframe: Up to 24 Week (From start of administration to the end of 6 cycles)

Population: Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey.

Outcome measures

Outcome measures
Measure	Ixazomib 4 mg n=742 Participants The usual adult dosage for oral administration was 4 mg as ixazomib, in the fasting state, once a day, once a week for 3 weeks (Days 1, 8, and 15), with a 13-day washout period (Days 16 through 28). This 4-week cycle was repeated for 6 cycles. The dose might be reduced appropriately according to the patient's condition. Participants received interventions as part of routine medical care.
Number of Participants Reporting One or More Adverse Events (AEs)	642 Participants

PRIMARY outcome

Timeframe: Up to 24 Week (From start of administration to the end of 6 cycles)

Population: Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey.

Outcome measures

Outcome measures
Measure	Ixazomib 4 mg n=742 Participants The usual adult dosage for oral administration was 4 mg as ixazomib, in the fasting state, once a day, once a week for 3 weeks (Days 1, 8, and 15), with a 13-day washout period (Days 16 through 28). This 4-week cycle was repeated for 6 cycles. The dose might be reduced appropriately according to the patient's condition. Participants received interventions as part of routine medical care.
Number of Participants Who Had One or More Adverse Drug Reactions (ADRs)	573 Participants

Adverse Events

Ixazomib 4 mg

Serious events: 193 serious events

Other events: 515 other events

Deaths: 11 deaths

Serious adverse events

Serious adverse events
Measure	Ixazomib 4 mg n=742 participants at risk The usual adult dosage for oral administration was 4 mg as ixazomib, in the fasting state, once a day, once a week for 3 weeks (Days 1, 8, and 15), with a 13-day washout period (Days 16 through 28). This 4-week cycle was repeated for 6 cycles. The dose might be reduced appropriately according to the patient's condition. Participants received interventions as part of routine medical care.
Infections and infestations Bacteraemia	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Bronchitis	0.40% 3/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Bronchopulmonary aspergillosis	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Escherichia sepsis	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Herpes zoster	0.67% 5/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Infection	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Influenza	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Pneumonia	3.0% 22/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Pneumonia cytomegaloviral	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Pneumonia haemophilus	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Pneumonia influenzal	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Pneumonia staphylococcal	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Pseudomembranous colitis	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Pyelonephritis	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Sepsis	0.67% 5/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Septic shock	0.54% 4/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Urinary tract infection	0.40% 3/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Candida sepsis	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Staphylococcal sepsis	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Enteritis infectious	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Intervertebral discitis	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Bacterial infection	0.54% 4/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Pneumonia bacterial	0.40% 3/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Infections and infestations Herpes zoster disseminated	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchioloalveolar carcinoma	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Blood and lymphatic system disorders Anaemia	0.94% 7/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Blood and lymphatic system disorders Febrile neutropenia	0.67% 5/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Blood and lymphatic system disorders Leukopenia	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Blood and lymphatic system disorders Neutropenia	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Blood and lymphatic system disorders Pancytopenia	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Blood and lymphatic system disorders Thrombocytopenia	9.8% 73/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Metabolism and nutrition disorders Dehydration	0.54% 4/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Metabolism and nutrition disorders Electrolyte imbalance	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Metabolism and nutrition disorders Hypokalaemia	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Metabolism and nutrition disorders Hyponatraemia	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Metabolism and nutrition disorders Tumour lysis syndrome	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Metabolism and nutrition disorders Malnutrition	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Metabolism and nutrition disorders Decreased appetite	0.94% 7/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Nervous system disorders Altered state of consciousness	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Nervous system disorders Dizziness	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Nervous system disorders Neuropathy peripheral	0.94% 7/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Nervous system disorders Thalamus haemorrhage	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Nervous system disorders Autonomic neuropathy	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Nervous system disorders Taste disorder	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Eye disorders Cataract	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Cardiac disorders Atrial fibrillation	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Cardiac disorders Atrioventricular block complete	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Cardiac disorders Atrioventricular block second degree	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Cardiac disorders Cardiac failure	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Cardiac disorders Cardiac failure acute	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Cardiac disorders Cardiac failure congestive	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Cardiac disorders Stress cardiomyopathy	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Vascular disorders Hypotension	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Vascular disorders Hypovolaemic shock	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Vascular disorders Orthostatic hypotension	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Respiratory, thoracic and mediastinal disorders Pulmonary alveolar haemorrhage	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Abdominal pain	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Colitis	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Diarrhoea	5.9% 44/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Gastrointestinal necrosis	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Haematemesis	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Ileus	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Intestinal obstruction	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Melaena	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Nausea	1.5% 11/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Pancreatitis acute	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Volvulus	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Vomiting	2.3% 17/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Tongue haemorrhage	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Mechanical ileus	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Hepatobiliary disorders Hepatic function abnormal	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Hepatobiliary disorders Hyperbilirubinaemia	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Hepatobiliary disorders Liver disorder	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Skin and subcutaneous tissue disorders Drug eruption	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Skin and subcutaneous tissue disorders Erythema multiforme	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Skin and subcutaneous tissue disorders Rash	0.40% 3/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Renal and urinary disorders Haematuria	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Renal and urinary disorders Renal disorder	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Renal and urinary disorders Renal failure	0.27% 2/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Renal and urinary disorders Renal impairment	0.40% 3/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Renal and urinary disorders Acute kidney injury	0.81% 6/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Renal and urinary disorders Prerenal failure	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
General disorders Death	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
General disorders Malaise	0.54% 4/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
General disorders Oedema	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
General disorders Pyrexia	0.40% 3/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Investigations Blood lactate dehydrogenase increased	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Investigations Neutrophil count decreased	1.9% 14/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Investigations Platelet count decreased	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Investigations Red blood cell count decreased	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Investigations White blood cell count decreased	1.2% 9/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Investigations C-reactive protein increased	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Investigations Blood creatinine increased	0.13% 1/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.

Other adverse events

Other adverse events
Measure	Ixazomib 4 mg n=742 participants at risk The usual adult dosage for oral administration was 4 mg as ixazomib, in the fasting state, once a day, once a week for 3 weeks (Days 1, 8, and 15), with a 13-day washout period (Days 16 through 28). This 4-week cycle was repeated for 6 cycles. The dose might be reduced appropriately according to the patient's condition. Participants received interventions as part of routine medical care.
Blood and lymphatic system disorders Thrombocytopenia	42.2% 313/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Nervous system disorders Neuropathy peripheral	6.1% 45/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Diarrhoea	24.0% 178/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Nausea	11.1% 82/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Gastrointestinal disorders Vomiting	7.0% 52/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.
Skin and subcutaneous tissue disorders Rash	7.0% 52/742 • Up to 24 Week (From start of administration to the end of 6 cycles) At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded. The data reported are only serious and the other (not including serious) ADRs by events because only serious and the other ADRs were planned to be collected and assessed in this study. Seriousness of AEs by events was out of the scope for the data collection plan.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER