Trial Outcomes & Findings for Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer (NCT NCT01441947)

NCT ID: NCT01441947

Last Updated: 2025-05-25

Results Overview

Bone scan response rate will be defined as the percentage of patients experiencing a complete resolution of bone lesions or partial response in the isotope bone scan per Bone Scan Time Point Response Criteria, as defined in the protocol. Complete resolution is defined as the disappearance of all areas of radiotracer uptake attributable to metastatic disease, and a partial response is defined as significant improvement in radiotracer uptake in areas attributable to metastatic disease, but not meeting the criteria for CR.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 68 participants
• Primary outcome timeframe: 2 years
• Results posted on: 2025-05-25

Participant Flow

Participant milestones

Measure	Cabozantinib Oral cabozantinib therapy daily Cabozantinib: Given orally daily with a starting dose of 40 mg	Cabozantinib Plus Fulvestrant Combination therapy with oral cabozantinib daily plus fulvestrant monthly Intramuscularly (IM) Cabozantinib: Given orally daily with a starting dose of 40 mg Fulvestrant: Given intramuscularly 500 mg on Days 1 and 15 of the first 28 day cycle, then on Day 1 only each cycle after
Overall Study STARTED	55	13
Overall Study COMPLETED	52	13
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Measure	Cabozantinib Oral cabozantinib therapy daily Cabozantinib: Given orally daily with a starting dose of 40 mg	Cabozantinib Plus Fulvestrant Combination therapy with oral cabozantinib daily plus fulvestrant monthly Intramuscularly (IM) Cabozantinib: Given orally daily with a starting dose of 40 mg Fulvestrant: Given intramuscularly 500 mg on Days 1 and 15 of the first 28 day cycle, then on Day 1 only each cycle after
Overall Study Withdrawal by Subject	3	0

Baseline Characteristics

Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer

Baseline characteristics by cohort

Measure	Cabozantinib n=55 Participants Oral cabozantinib therapy daily Cabozantinib: Given orally daily with a starting dose of 40 mg	Cabozantinib Plus Fulvestrant n=13 Participants Combination therapy with oral cabozantinib daily plus fulvestrant monthly Intramuscularly (IM) Cabozantinib: Given orally daily with a starting dose of 40 mg Fulvestrant: Given intramuscularly 500 mg on Days 1 and 15 of the first 28 day cycle, then on Day 1 only each cycle after	Total n=68 Participants Total of all reporting groups
Age, Continuous	55 years n=5 Participants	63 years n=7 Participants	56 years n=5 Participants
Sex: Female, Male Female	55 Participants n=5 Participants	13 Participants n=7 Participants	68 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants n=5 Participants	12 Participants n=7 Participants	56 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	1 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	45 Participants n=5 Participants	12 Participants n=7 Participants	57 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Population: 55 patients initially enrolled to the Cabozantinib cohort, but 3 withdrew prior to starting study treatment. Per protocol section 14.1, only patients in the main cabozantinib cohort were included in the primary analysis. There are no primary endpoints for the pilot cabozantinib/ fulvestrant cohort.

Bone scan response rate will be defined as the percentage of patients experiencing a complete resolution of bone lesions or partial response in the isotope bone scan per Bone Scan Time Point Response Criteria, as defined in the protocol. Complete resolution is defined as the disappearance of all areas of radiotracer uptake attributable to metastatic disease, and a partial response is defined as significant improvement in radiotracer uptake in areas attributable to metastatic disease, but not meeting the criteria for CR.

Outcome measures

Measure	Cabozantinib n=52 Participants Oral cabozantinib therapy daily Cabozantinib: Given orally daily with a starting dose of 40 mg
Bone Scan Response Rate	38.5 percentage of participants Interval 27.1 to 51.0

SECONDARY outcome

Timeframe: 2 years

Population: 55 patients initially enrolled to the Cabozantinib cohort, but 3 withdrew prior to starting study treatment. Per protocol section 14.4, ORR is a secondary endpoint only for the main cabozantinib cohort; endpoints for the pilot cohort are listed separately. Additionally, per protocol section 14.4, "All secondary endpoint analyses of this trial are considered exploratory." Results for ORR are available, so we are reporting them here even though this endpoint was considered exploratory.

The overall response rate (ORR) is defined as the percentage of patients experiencing a complete response or partial response on PET imaging per mRECIST (modified response evaluation criteria in solid tumors), as defined in the protocol. A complete response is defined as resolution of all areas of FDG uptake attributable to metastatic disease. A partial response is defined as significantly decreased FDG uptake in areas attributable to metastatic disease, but not meeting the criteria for a complete response.

Outcome measures

Measure	Cabozantinib n=52 Participants Oral cabozantinib therapy daily Cabozantinib: Given orally daily with a starting dose of 40 mg
Overall Response Rate by RECIST v 1.1	0 Participants

SECONDARY outcome

Timeframe: 5 years

Population: 55 patients initially enrolled to the Cabozantinib cohort, but 3 withdrew prior to starting study treatment. Per protocol section 14.4, OS is a secondary endpoint only for the main cabozantinib cohort; endpoints for the pilot cohort are listed separately. Additionally, per protocol section 14.4, "All secondary endpoint analyses of this trial are considered exploratory." Results for OS are available, so we are reporting them here even though this endpoint was considered exploratory.

Overall Survival (OS) is defined as the difference between the date of a patient's enrollment onto this study until the date of death. Patients who are alive at last contact will be censored for OS at this date.

Outcome measures

Measure	Cabozantinib n=52 Participants Oral cabozantinib therapy daily Cabozantinib: Given orally daily with a starting dose of 40 mg
Overall Survival	19.6 months Interval 18.0 to 26.8

SECONDARY outcome

Timeframe: 5 years

Population: 55 patients initially enrolled to the Cabozantinib cohort, but 3 withdrew prior to starting study treatment. Per protocol section 14.4, PFS is a secondary endpoint only for the main cabozantinib cohort; endpoints for the pilot cohort are listed separately. Additionally, per protocol section 14.4, "All secondary endpoint analyses of this trial are considered exploratory." Results for PFS are available, so we are reporting them here even though this endpoint was considered exploratory.

Progression Free Survival (PFS) is defined as the difference between the date of a patient's enrollment onto this study until the earlier of the date of progression or the date of death. Patients who are alive and progression-free at last contact will be censored for PFS at this date.

Outcome measures

Measure	Cabozantinib n=52 Participants Oral cabozantinib therapy daily Cabozantinib: Given orally daily with a starting dose of 40 mg
Progression Free Survival	4.3 units on a scale Interval 2.8 to 5.5

Adverse Events

Cabozantinib

Serious events: 13 serious events

Other events: 51 other events

Deaths: 35 deaths

Cabozantinib Plus Fulvestrant

Serious events: 3 serious events

Other events: 13 other events

Deaths: 12 deaths

Serious adverse events

Measure	Cabozantinib n=52 participants at risk Oral cabozantinib therapy daily Cabozantinib: Given orally daily with a starting dose of 40 mg	Cabozantinib Plus Fulvestrant n=13 participants at risk Combination therapy with oral cabozantinib daily plus fulvestrant monthly Intramuscularly (IM) Cabozantinib: Given orally daily with a starting dose of 40 mg Fulvestrant: Given intramuscularly 500 mg on Days 1 and 15 of the first 28 day cycle, then on Day 1 only each cycle after
Injury, poisoning and procedural complications Pathologic left femur fracture	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Vulval Infection	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Concentration Impairment	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Injury, poisoning and procedural complications Fractured C7, T5	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders Death	5.8% 3/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Blood and lymphatic system disorders febrile neutropenia	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Renal and urinary disorders Acute Interstitial Nephritis	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Shortness of Breath	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hypercalcemia	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Injury, poisoning and procedural complications Impending pathologic fracture	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Urinary Tract Infection	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hyponatremia	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Pneumonia	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Cardiac disorders Decrease in LVEF	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Dehydration	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hypokalemia	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Respiratory Failure	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Bilateral pulmonary embolism	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Vascular disorders Vascular access complication	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Colitis	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Blood and lymphatic system disorders Neutropenia	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)

Other adverse events

Measure	Cabozantinib n=52 participants at risk Oral cabozantinib therapy daily Cabozantinib: Given orally daily with a starting dose of 40 mg	Cabozantinib Plus Fulvestrant n=13 participants at risk Combination therapy with oral cabozantinib daily plus fulvestrant monthly Intramuscularly (IM) Cabozantinib: Given orally daily with a starting dose of 40 mg Fulvestrant: Given intramuscularly 500 mg on Days 1 and 15 of the first 28 day cycle, then on Day 1 only each cycle after
Nervous system disorders Cognitive disturbance	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Abdominal pain	5.8% 3/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	30.8% 4/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Activated partial thromboplastin time prolonged	5.8% 3/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Alanine aminotransferase increased	53.8% 28/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	38.5% 5/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Alkaline phosphatase increased	36.5% 19/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Alopecia	13.5% 7/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Blood and lymphatic system disorders Anemia	11.5% 6/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Anorexia	36.5% 19/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	61.5% 8/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Psychiatric disorders Anxiety	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Aphonia	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Arthralgia	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	30.8% 4/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Aspartate aminotransferase increased	53.8% 28/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	38.5% 5/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Ataxia	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Back pain	26.9% 14/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Bloating	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify: decreased hemoglobin	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify: decreased potassium	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Blood bilirubin increased	9.6% 5/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Eye disorders Blurred vision	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Bone pain	34.6% 18/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Reproductive system and breast disorders Breast pain	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Injury, poisoning and procedural complications Bruising	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Buttock pain	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Cardiac disorders Cardiac disorders - Other, specify: cardiac arrhythmia	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Cardiac disorders Cardiac disorders - Other, specify	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations CD4 lymphocytes decreased	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders Chills	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Chylothorax	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Colitis	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Concentration impairment	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Constipation	28.8% 15/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Cough	19.2% 10/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Creatinine increased	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Dehydration	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Psychiatric disorders Depression	7.7% 4/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Diarrhea	50.0% 26/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	46.2% 6/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Dizziness	9.6% 5/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Eye disorders Dry eye	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Dry mouth	7.7% 4/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Dry skin	9.6% 5/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	30.8% 4/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Duodenal hemorrhage	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Dysesthesia	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Dysgeusia	17.3% 9/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Dyspepsia	19.2% 10/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Dysphagia	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Dyspnea	11.5% 6/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Ear and labyrinth disorders Ear and labyrinth disorders - Other, specify: ear block	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders Edema face	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders Edema limbs	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	30.8% 4/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Endocrine disorders Endocrine disorders - Other, specify: TSH elevation	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Erythema multiforme	11.5% 6/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Esophagitis	9.6% 5/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Extrapyramidal disorder	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Eye disorders Eye disorders - Other, specify: change in iris color	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Eye disorders Eye disorders - Other, specify: Diplopia	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders Facial pain	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Injury, poisoning and procedural complications Fall	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Fat atrophy	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders Fatigue	71.2% 37/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	76.9% 10/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Blood and lymphatic system disorders Febrile neutropenia	9.6% 5/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders Fever	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Flank pain	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Flatulence	7.7% 4/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Vascular disorders Flushing	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Injury, poisoning and procedural complications Fracture	5.8% 3/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders Gait disturbance	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Gastroesophageal reflux disease	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	38.5% 5/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Oral petichiae/papules	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: heart burn	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: taste alteration	15.4% 8/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: reflux	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Stomatitis	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Tongue soreness	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: loose stool	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Gastrointestinal pain	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Gastroparesis	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders General disorders and administration site conditions - Other, specify: hair turning grey	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders General disorders and administration site conditions - Other, specify: oral thrush	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders General disorders and administration site conditions - Other, specify: jaw numbness	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Generalized muscle weakness	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders General disorders and administration site conditions - Other, specify: feet sensitivities	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Gingival pain	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Gum infection	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Headache	25.0% 13/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	30.8% 4/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Hemoglobin increased	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Renal and urinary disorders Hemoglobinuria	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Hemorrhoids	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Hepatobiliary disorders Hepatobiliary disorders - Other, specify: LDH elevation	13.5% 7/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Hiccups	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Hoarseness	23.1% 12/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Vascular disorders Hot flashes	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Hydrocephalus	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hypercalcemia	5.8% 3/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hyperglycemia	28.8% 15/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Hyperhidrosis	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hyperkalemia	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hypermagnesemia	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hypernatremia	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Endocrine disorders Hyperparathyroidism	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Vascular disorders Hypertension	32.7% 17/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Endocrine disorders Hyperthyroidism	7.7% 4/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hypoalbuminemia	11.5% 6/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hypocalcemia	11.5% 6/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hypoglycemia	5.8% 3/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hypokalemia	15.4% 8/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hypomagnesemia	5.8% 3/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hyponatremia	15.4% 8/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Endocrine disorders Hypoparathyroidism	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Hypophosphatemia	25.0% 13/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Endocrine disorders Hypothyroidism	23.1% 12/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	38.5% 5/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders Injection site reaction	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Investigations - Other, specify: Decreased hemoglobin	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Investigations - Other, specify: TSH elevation	9.6% 5/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Investigations - Other, specify: total protein decreased	5.8% 3/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Investigations - Other, specify	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Investigations - Other, specify: thrombocytosis	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Investigations - Other, specify: Urine Protein Creatinine Ratio - present at baseline	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Investigations - Other, specify: blood urea nitrogen increased	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Investigations - Other, specify: amylase increased	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Investigations - Other, specify: white blood cells in urine	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Laryngeal mucositis	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Laryngitis	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Lipase increased	13.5% 7/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Lung infection	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Blood and lymphatic system disorders Lymph node pain	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Lymphocyte count decreased	23.1% 12/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Mediastinal infection	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Memory impairment	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify: hypochloridemia	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Mucosal infection	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Mucositis oral	36.5% 19/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	38.5% 5/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: leg cramping	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	5.8% 3/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: achiness	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: left leg pain	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: right shoulder pain	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: right rib pain	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: hand cramps	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: muscle cramps	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: joint stiffness	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: bilateral leg heaviness	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: pleuritic pain	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Myalgia	7.7% 4/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Nail ridging	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Nausea	46.2% 24/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	46.2% 6/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Neck pain	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Nervous system disorders - Other, specify: dysphonia	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Nervous system disorders - Other, specify: neuropathy in fingers	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Nervous system disorders - Other, specify: intermittent lightheadedness	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Nervous system disorders - Other, specify: right leg nerve pain	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Neutrophil count decreased	9.6% 5/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders Non-cardiac chest pain	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Oral dysesthesia	9.6% 5/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Oral hemorrhage	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Oral pain	5.8% 3/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
General disorders Pain	32.7% 17/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	53.8% 7/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Musculoskeletal and connective tissue disorders Pain in extremity	15.4% 8/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	48.1% 25/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Cardiac disorders Palpitations	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Papulopustular rash	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Reproductive system and breast disorders Pelvic pain	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Peripheral motor neuropathy	5.8% 3/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Peripheral sensory neuropathy	17.3% 9/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Vascular disorders Phlebitis	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Platelet count decreased	11.5% 6/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Renal and urinary disorders Proteinuria	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Rash acneiform	9.6% 5/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Rash maculo-papular	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify: dysphonia	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify: pulmonary embolus	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Rhinitis infective	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Salivary gland infection	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Serum amylase increased	9.6% 5/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Sinusitis	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: skin rash	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: hair thinning	9.6% 5/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: hair depigmentation	13.5% 7/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: skin peeling bilateral soles of feet	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: acne vulgaris	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: tick bite	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: hair discoloration	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: right great toe ingrown toenail	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: wart	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: rash on scalp	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: rash on arms	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: rash	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: tender soles of feet	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin hypopigmentation	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Skin infection	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: PPE	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Sore throat	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	15.4% 2/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Nervous system disorders Spasticity	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Stomach pain	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Tooth infection	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Toothache	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Upper gastrointestinal hemorrhage	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Upper respiratory infection	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Renal and urinary disorders Urinary incontinence	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Renal and urinary disorders Urinary retention	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Infections and infestations Urinary tract infection	5.8% 3/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	23.1% 3/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Reproductive system and breast disorders Vaginal discharge	0.00% 0/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Respiratory, thoracic and mediastinal disorders Voice alteration	3.8% 2/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Gastrointestinal disorders Vomiting	19.2% 10/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Weight gain	1.9% 1/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	0.00% 0/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations Weight loss	28.8% 15/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	30.8% 4/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)
Investigations White blood cell decreased	34.6% 18/52 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)	7.7% 1/13 • Adverse event reporting will begin from the time of the first dose of study treatment, through the study and until the final study visit (up to 5 years)

Additional Information

Steven Isakoff, MD, PhD

Massachusetts General Hospital

Phone: 617-643-5415

Email: sisakoff@partners.org

Results disclosure agreements

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