Trial Outcomes & Findings for S1312, Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Leukemia (NCT NCT01925131)

NCT ID: NCT01925131

Last Updated: 2023-05-03

Results Overview

To determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in this regimen for patients with relapsed or refractory CD22+ acute leukemia (B-cell acute lymphoblastic leukemia \[B-ALL\], mixed phenotype, and Burkitt's). The MTD is defined as the highest dose studied in which the incidence of dose-limiting toxicities is \< 33% using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 50 participants
• Primary outcome timeframe: 28 days
• Results posted on: 2023-05-03

Participant Flow

There were a total of 50 participants enrolled. However, two were deemed ineligible due to inadequate liver function and did not start protocol treatment, leaving 48 eligible participants.

Participant milestones

Measure	CVP + Inotuzumab Dose Level 1 Combination chemotherapy and inotuzumab ozogamicin - Dose level 1 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 2 Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 3 Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 4 Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 5 Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab MTD (Expansion Cohort) Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose (Expansion Cohort) Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	5	4	10	5	11	13
Overall Study COMPLETED	0	2	1	0	0	3
Overall Study NOT COMPLETED	5	2	9	5	11	10

Reasons for withdrawal

Measure	CVP + Inotuzumab Dose Level 1 Combination chemotherapy and inotuzumab ozogamicin - Dose level 1 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 2 Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 3 Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 4 Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 5 Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab MTD (Expansion Cohort) Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose (Expansion Cohort) Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Overall Study Death	0	0	1	0	0	0
Overall Study Progression/Relapse	1	1	4	0	0	1
Overall Study Patient Refusal	1	0	0	0	0	0
Overall Study Adverse Event	0	0	2	0	1	3
Overall Study Other - Not Protocol Specified	3	1	2	5	10	6

Baseline Characteristics

S1312, Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Leukemia

Baseline characteristics by cohort

Measure	CVP + Inotuzumab Dose Level 1 n=5 Participants Combination chemotherapy and inotuzumab ozogamicin � Dose level 1 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 2 n=4 Participants Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 3 n=10 Participants Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 4 n=5 Participants Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 5 n=11 Participants Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab MTD n=13 Participants Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Total n=48 Participants Total of all reporting groups
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	5 Participants n=8 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	7 Participants n=21 Participants	8 Participants n=8 Participants	33 Participants n=8 Participants
Age, Continuous	48.8 years n=5 Participants	42.3 years n=7 Participants	42.8 years n=5 Participants	49.6 years n=4 Participants	37.9 years n=21 Participants	43.5 years n=8 Participants	43 years n=8 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants	5 Participants n=8 Participants	21 Participants n=8 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants	8 Participants n=8 Participants	27 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=8 Participants	16 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants	9 Participants n=8 Participants	28 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=8 Participants	4 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	3 Participants n=8 Participants	4 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=8 Participants	6 Participants n=8 Participants

PRIMARY outcome

Timeframe: 28 days

Population: Includes eligible patients who received treatment among all arms.

To determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in this regimen for patients with relapsed or refractory CD22+ acute leukemia (B-cell acute lymphoblastic leukemia [B-ALL], mixed phenotype, and Burkitt's). The MTD is defined as the highest dose studied in which the incidence of dose-limiting toxicities is < 33% using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

Outcome measures

Measure	CVP + Inotuzumab n=48 Participants Combination chemotherapy and inotuzumab ozogamicin Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 2 Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 3 Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 4 Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 5 Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab MTD Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
MTD of Inotuzumab Ozogamicin With CVP for Patients With Relapsed or Refractory CD22+ Acute Leukemia Day 1 Dose	0.8 mg/m^2	—	—	—	—	—
MTD of Inotuzumab Ozogamicin With CVP for Patients With Relapsed or Refractory CD22+ Acute Leukemia Day 8 Dose	0.5 mg/m^2	—	—	—	—	—
MTD of Inotuzumab Ozogamicin With CVP for Patients With Relapsed or Refractory CD22+ Acute Leukemia Day 15 Dose	0.5 mg/m^2	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: MTD arm only, including eligible patients who received treatment and were evaluable for response

The response rate (CR + CRi) is defined as the rate of complete remission (CR) + complete remission with incomplete count recovery (CRi). Complete remission (CR) is defined as < 5% marrow aspirate blasts, neutrophils ≥ 1000/uL, platelets > 100,000/uL, no blasts in peripheral blood, and C1 Extramedullary disease status. C1 Extramedullary disease status is characterized by complete disappearance of all measurable and non-measurable extramedullary disease with the exception of lesions for which the following must be true: for participants with at least one measurable lesion, all lesions must have reduced by 75% in sum of products of greatest diameters (SPD), have no new lesions, and the spleen and other previously enlarged organs must have regressed in size. Complete remission with incomplete platelet recovery (CRi) is defined the same as CR, except absolute neutrophil count may be <1000/uL and/or platelet count may be ≤ 100,000/uL.

Outcome measures

Measure	CVP + Inotuzumab n=12 Participants Combination chemotherapy and inotuzumab ozogamicin Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 2 Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 3 Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 4 Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 5 Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab MTD Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Response Rate (CR+CRi) Among Expansion Cohort	83.33 percentage of participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: Eligible participants who received at least one dose of protocol treatment.

Number of participants with Grade 3-5 adverse events that are possibly, probably or definitely related to study drug are reported by given type of adverse event.

Outcome measures

Measure	CVP + Inotuzumab n=5 Participants Combination chemotherapy and inotuzumab ozogamicin Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 2 n=4 Participants Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 3 n=10 Participants Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 4 n=5 Participants Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 5 n=11 Participants Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab MTD n=13 Participants Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Frequency and Severity of Toxicities Hypertension	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants
Frequency and Severity of Toxicities Anemia	2 Participants	2 Participants	7 Participants	3 Participants	5 Participants	5 Participants
Frequency and Severity of Toxicities Ascites	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Frequency and Severity of Toxicities Dysphagia	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Frequency and Severity of Toxicities Encephalopathy	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Frequency and Severity of Toxicities Enterocolitis	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Frequency and Severity of Toxicities Fatigue	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Frequency and Severity of Toxicities Febrile neutropenia	0 Participants	2 Participants	2 Participants	3 Participants	1 Participants	7 Participants
Frequency and Severity of Toxicities Fever	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Frequency and Severity of Toxicities Gastric hemorrhage	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Frequency and Severity of Toxicities Gastrointestinal disorders - Other, specify	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Frequency and Severity of Toxicities Headache	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Frequency and Severity of Toxicities Hyperglycemia	0 Participants	0 Participants	4 Participants	4 Participants	2 Participants	0 Participants
Frequency and Severity of Toxicities Hypoalbuminemia	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Frequency and Severity of Toxicities Hypocalcemia	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Frequency and Severity of Toxicities Hypokalemia	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Frequency and Severity of Toxicities Infections and infestations - Other, specify	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	4 Participants
Frequency and Severity of Toxicities Intracranial hemorrhage	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Frequency and Severity of Toxicities Lipase increased	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Frequency and Severity of Toxicities Lung infection	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Frequency and Severity of Toxicities Lymphocyte count decreased	2 Participants	1 Participants	3 Participants	3 Participants	6 Participants	6 Participants
Frequency and Severity of Toxicities Mucositis oral	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Frequency and Severity of Toxicities Neutrophil count decreased	3 Participants	3 Participants	9 Participants	4 Participants	8 Participants	8 Participants
Frequency and Severity of Toxicities Platelet count decreased	2 Participants	2 Participants	7 Participants	4 Participants	5 Participants	10 Participants
Frequency and Severity of Toxicities Renal and urinary disorders - Other, specify	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Frequency and Severity of Toxicities Sepsis	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Frequency and Severity of Toxicities Skin infection	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Frequency and Severity of Toxicities White blood cell decreased	3 Participants	4 Participants	10 Participants	5 Participants	7 Participants	9 Participants

Adverse Events

CVP + Inotuzumab Dose Level 1

Serious events: 2 serious events

Other events: 5 other events

Deaths: 4 deaths

CVP + Inotuzumab Dose Level 2

Serious events: 2 serious events

Other events: 4 other events

Deaths: 3 deaths

CVP + Inotuzumab Dose Level 3

Serious events: 4 serious events

Other events: 10 other events

Deaths: 9 deaths

CVP + Inotuzumab Dose Level 4

Serious events: 1 serious events

Other events: 5 other events

Deaths: 5 deaths

CVP + Inotuzumab Dose Level 5

Serious events: 1 serious events

Other events: 11 other events

Deaths: 9 deaths

CVP + Inotuzumab MTD

Serious events: 11 serious events

Other events: 13 other events

Deaths: 8 deaths

Serious adverse events

Measure	CVP + Inotuzumab Dose Level 1 n=5 participants at risk Combination chemotherapy and inotuzumab ozogamicin � Dose level 1 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 2 n=4 participants at risk Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 3 n=10 participants at risk Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 4 n=5 participants at risk Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 5 n=11 participants at risk Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab MTD n=13 participants at risk Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Cardiac disorders Sinus tachycardia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Ascites	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Gastric hemorrhage	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Gastrointestinal disorders-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Edema face	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Facial pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Fatigue	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Fever	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Infections and infestations-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	38.5% 5/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Lung infection	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Sinusitis	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Upper respiratory infection	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Investigations-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Encephalopathy	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Headache	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Intracranial hemorrhage	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Nervous system disorders-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Seizure	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Syncope	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Renal and urinary disorders Renal and urinary disorders-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Vascular disorders Hematoma	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Vascular disorders Hypotension	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Vascular disorders Thromboembolic event	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.

Other adverse events

Measure	CVP + Inotuzumab Dose Level 1 n=5 participants at risk Combination chemotherapy and inotuzumab ozogamicin � Dose level 1 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 2 n=4 participants at risk Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 3 n=10 participants at risk Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 4 n=5 participants at risk Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab Dose Level 5 n=11 participants at risk Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	CVP + Inotuzumab MTD n=13 participants at risk Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	75.0% 3/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	90.0% 9/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	100.0% 5/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	90.9% 10/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	69.2% 9/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	18.2% 2/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	61.5% 8/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Blood and lymphatic system disorders Lymph node pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Cardiac disorders Atrial fibrillation	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Cardiac disorders Cardiac disorders-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Cardiac disorders Palpitations	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Cardiac disorders Sinus bradycardia	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Cardiac disorders Sinus tachycardia	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 6/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	80.0% 4/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	36.4% 4/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Cardiac disorders Ventricular tachycardia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Ear and labyrinth disorders Ear and labyrinth disorders-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Ear and labyrinth disorders Ear pain	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Ear and labyrinth disorders Vertigo	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Endocrine disorders Hypothyroidism	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Eye disorders Blurred vision	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Eye disorders Conjunctivitis	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Eye disorders Dry eye	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Eye disorders Eye disorders-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Eye disorders Eye pain	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Eye disorders Photophobia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Eye disorders Watering eyes	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Abdominal distension	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Abdominal pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	53.8% 7/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Ascites	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Constipation	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	27.3% 3/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	38.5% 5/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Diarrhea	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	50.0% 2/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.0% 3/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.8% 4/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Dry mouth	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Dyspepsia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Dysphagia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Enterocolitis	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Fecal incontinence	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Flatulence	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Gastric hemorrhage	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Gastrointestinal disorders-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.8% 4/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Gingival pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Hemorrhoids	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Mucositis oral	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Nausea	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	50.0% 2/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	50.0% 5/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	18.2% 2/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	46.2% 6/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Oral hemorrhage	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Oral pain	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Periodontal disease	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Stomach pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Toothache	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Gastrointestinal disorders Vomiting	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	23.1% 3/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Chills	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	61.5% 8/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Edema face	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Edema limbs	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 6/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	18.2% 2/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.8% 4/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Facial pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Fatigue	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	50.0% 2/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.0% 3/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	45.5% 5/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	38.5% 5/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Fever	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	50.0% 2/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.8% 4/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Flu like symptoms	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Gait disturbance	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders General disorders and admin site conditions - Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.8% 4/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Infusion related reaction	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Injection site reaction	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Localized edema	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Malaise	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Non-cardiac chest pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
General disorders Pain	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 4/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Immune system disorders Allergic reaction	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Catheter related infection	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Enterocolitis infectious	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Infections and infestations-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	38.5% 5/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Lung infection	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Rash pustular	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Sepsis	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.8% 4/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Sinusitis	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Skin infection	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Infections and infestations Urinary tract infection	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Injury, poisoning and procedural complications Bruising	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Injury, poisoning and procedural complications Fall	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Injury, poisoning and procedural complications Postoperative hemorrhage	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Alanine aminotransferase increased	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	45.5% 5/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	46.2% 6/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Alkaline phosphatase increased	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 4/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	80.0% 4/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	63.6% 7/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Aspartate aminotransferase increased	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	75.0% 3/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	63.6% 7/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Blood bilirubin increased	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	50.0% 2/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.0% 3/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	38.5% 5/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Cholesterol high	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Creatinine increased	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Fibrinogen decreased	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations INR increased	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Investigations-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Lipase increased	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Lymphocyte count decreased	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	50.0% 2/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.0% 3/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	63.6% 7/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	46.2% 6/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Neutrophil count decreased	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	75.0% 3/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	90.0% 9/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	80.0% 4/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	90.9% 10/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	69.2% 9/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Platelet count decreased	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	75.0% 3/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	80.0% 8/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	100.0% 5/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	90.9% 10/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	76.9% 10/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Weight gain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations Weight loss	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Investigations White blood cell decreased	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	100.0% 4/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	100.0% 10/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	100.0% 5/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	90.9% 10/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	76.9% 10/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Acidosis	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Anorexia	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.0% 3/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Dehydration	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hyperglycemia	80.0% 4/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	50.0% 5/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	80.0% 4/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	63.6% 7/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hyperkalemia	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hypermagnesemia	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	18.2% 2/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hypertriglyceridemia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hypoalbuminemia	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	50.0% 2/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 6/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	80.0% 4/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	81.8% 9/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	46.2% 6/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hypocalcemia	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	50.0% 2/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 4/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	27.3% 3/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	27.3% 3/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hypokalemia	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	75.0% 3/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.0% 3/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	72.7% 8/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	23.1% 3/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hypomagnesemia	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	27.3% 3/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hyponatremia	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 4/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	27.3% 3/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Obesity	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Metabolism and nutrition disorders Tumor lysis syndrome	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Arthritis	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Back pain	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	27.3% 3/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	23.1% 3/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Chest wall pain	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tiss disorder - Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.8% 4/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Neck pain	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Musculoskeletal and connective tissue disorders Pain in extremity	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.0% 3/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	27.3% 3/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.8% 4/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Dizziness	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	23.1% 3/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Dysarthria	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Encephalopathy	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Facial muscle weakness	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Headache	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.0% 3/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	27.3% 3/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	53.8% 7/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Intracranial hemorrhage	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Lethargy	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	18.2% 2/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Memory impairment	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Nervous system disorders-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Paresthesia	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Peripheral motor neuropathy	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Peripheral sensory neuropathy	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	27.3% 3/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	46.2% 6/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Somnolence	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Nervous system disorders Tremor	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Psychiatric disorders Agitation	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.0% 3/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Psychiatric disorders Anxiety	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.0% 3/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	18.2% 2/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Psychiatric disorders Confusion	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Psychiatric disorders Delirium	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Psychiatric disorders Depression	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Psychiatric disorders Insomnia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	27.3% 3/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Psychiatric disorders Personality change	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Psychiatric disorders Psychiatric disorders-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Psychiatric disorders Restlessness	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Renal and urinary disorders Acute kidney injury	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Renal and urinary disorders Chronic kidney disease	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Renal and urinary disorders Hematuria	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Renal and urinary disorders Proteinuria	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	18.2% 2/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Renal and urinary disorders Renal and urinary disorders-Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Renal and urinary disorders Urinary frequency	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Renal and urinary disorders Urinary incontinence	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Renal and urinary disorders Urinary retention	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Renal and urinary disorders Urinary tract pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Renal and urinary disorders Urinary urgency	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Reproductive system and breast disorders Menorrhagia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Reproductive system and breast disorders Penile pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Reproductive system and breast disorders Scrotal pain	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Reproductive system and breast disorders Vaginal hemorrhage	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Reproductive system and breast disorders Vaginal inflammation	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Atelectasis	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Cough	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.0% 3/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	18.2% 2/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.8% 4/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	18.2% 2/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	50.0% 2/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	23.1% 3/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Hoarseness	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Laryngeal hemorrhage	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Postnasal drip	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Resp, thoracic and mediastinal disorders - Other	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Skin and subcutaneous tissue disorders Bullous dermatitis	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	30.0% 3/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Skin and subcutaneous tissue disorders Hyperhidrosis	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	27.3% 3/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Skin and subcutaneous tissue disorders Periorbital edema	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	9.1% 1/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Skin and subcutaneous tissue disorders Purpura	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 2/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 2/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	15.4% 2/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Skin and subcutaneous tissue disorders Skin ulceration	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Vascular disorders Flushing	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Vascular disorders Hypertension	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	25.0% 1/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	40.0% 4/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	60.0% 3/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	45.5% 5/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	23.1% 3/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Vascular disorders Hypotension	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	10.0% 1/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	23.1% 3/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Vascular disorders Lymphedema	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	7.7% 1/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.
Vascular disorders Thromboembolic event	0.00% 0/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/4 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/10 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	20.0% 1/5 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/11 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.	0.00% 0/13 • Up to 3 years post registration All adverse events, regardless of attribution and grade, are reported.

Additional Information

SWOG Statistician

SWOG Statistics and Data Management Center

Phone: 2066674623

Email: amoseley@fredhutch.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60