Trial Outcomes & Findings for Testing the PD-1 Inhibitor Pembrolizumab as Maintenance Therapy After Initial Chemotherapy in Metastatic Bladder Cancer (NCT NCT02500121)

NCT ID: NCT02500121

Last Updated: 2022-09-30

Results Overview

Measured at the time from randomization to death or progression, depending on which occurs first, as per immune-related RECIST (irRECIST). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 108 participants
• Primary outcome timeframe: Calculated after a median follow-up time of 12.9 months
• Results posted on: 2022-09-30

Participant Flow

Participant milestones

Measure	Control Arm A Commercially available normal saline will be used as the placebo. No active placebo drug will be mixed with the normal saline. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Placebo: Normal saline	Experimental Arm B Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Pembrolizumab: Pembrolizumab, 200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or for up to 24 months
Overall Study STARTED	53	55
Overall Study Crossover to Pembrolizumab	27	0
Overall Study COMPLETED	26	29
Overall Study NOT COMPLETED	27	26

Reasons for withdrawal

Measure	Control Arm A Commercially available normal saline will be used as the placebo. No active placebo drug will be mixed with the normal saline. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Placebo: Normal saline	Experimental Arm B Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Pembrolizumab: Pembrolizumab, 200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or for up to 24 months
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	1	1
Overall Study Death	26	24

Baseline Characteristics

Testing the PD-1 Inhibitor Pembrolizumab as Maintenance Therapy After Initial Chemotherapy in Metastatic Bladder Cancer

Baseline characteristics by cohort

Measure	Control Arm A n=52 Participants Commercially available normal saline will be used as the placebo. No active placebo drug will be mixed with the normal saline. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Placebo: Normal saline	Experimental Arm B n=55 Participants Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Pembrolizumab: Pembrolizumab, 200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or for up to 24 months	Total n=107 Participants Total of all reporting groups
Age, Continuous	65 years n=93 Participants	68 years n=4 Participants	66 years n=27 Participants
Sex: Female, Male Female	10 Participants n=93 Participants	16 Participants n=4 Participants	26 Participants n=27 Participants
Sex: Female, Male Male	42 Participants n=93 Participants	39 Participants n=4 Participants	81 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	3 Participants n=93 Participants	4 Participants n=4 Participants	7 Participants n=27 Participants
Race (NIH/OMB) White	46 Participants n=93 Participants	50 Participants n=4 Participants	96 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Region of Enrollment United States	52 participants n=93 Participants	55 participants n=4 Participants	107 participants n=27 Participants
Presence of Visceral Metastatic Disease at time of Initiation of First Line Chemotherapy	32 Participants n=93 Participants	39 Participants n=4 Participants	71 Participants n=27 Participants
ECOG Performance Score ECOG 0	23 Participants n=93 Participants	22 Participants n=4 Participants	45 Participants n=27 Participants
ECOG Performance Score ECOG 1	29 Participants n=93 Participants	33 Participants n=4 Participants	62 Participants n=27 Participants
Cycles of First-Line Chemotherapy	6 cycles n=93 Participants	6 cycles n=4 Participants	6 cycles n=27 Participants
Best Response to First Line Chemotherapy Complete Response/Partial Response	36 Participants n=93 Participants	40 Participants n=4 Participants	76 Participants n=27 Participants
Best Response to First Line Chemotherapy Stable Disease	16 Participants n=93 Participants	15 Participants n=4 Participants	31 Participants n=27 Participants
Cisplatin based First Line Chemotherapy	40 Participants n=93 Participants	40 Participants n=4 Participants	80 Participants n=27 Participants

PRIMARY outcome

Timeframe: Calculated after a median follow-up time of 12.9 months

Population: One patient randomly assigned to placebo was excluded from the analysis because of inconsistent receipt of pembrolizumab rather than placebo during the initial several cycles of study treatment.

Measured at the time from randomization to death or progression, depending on which occurs first, as per immune-related RECIST (irRECIST). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Outcome measures

Measure	Control Arm A n=52 Participants Commercially available normal saline will be used as the placebo. No active placebo drug will be mixed with the normal saline. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Placebo: Normal saline	Experimental Arm B n=55 Participants Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Pembrolizumab: Pembrolizumab, 200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or for up to 24 months
Progression-free Survival (PFS)	3.0 months Interval 2.7 to 5.5	5.4 months Interval 3.1 to 7.3

SECONDARY outcome

Timeframe: Six months after randomization

Population: One patient randomly assigned to placebo was excluded from the analysis because of inconsistent receipt of pembrolizumab rather than placebo during the initial several cycles of study treatment.

Probability that subjects remain alive and progression free at 6 months post randomization per irRECIST criteria. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure	Control Arm A n=52 Participants Commercially available normal saline will be used as the placebo. No active placebo drug will be mixed with the normal saline. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Placebo: Normal saline	Experimental Arm B n=55 Participants Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Pembrolizumab: Pembrolizumab, 200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or for up to 24 months
6-month PFS as Per irRECIST	0.2551 probability	0.4101 probability

SECONDARY outcome

Timeframe: Every 3 weeks beginning with C1D1 for up to 24 months

Population: One patient randomly assigned to placebo was excluded from the analysis because of inconsistent receipt of pembrolizumab rather than placebo during the initial several cycles of study treatment.

Percentage of subjects with treatment-emergent grade 3-4 toxicities, as per Common Terminology Criteria for Adverse Events (CTCAE) v 4.0

Outcome measures

Measure	Control Arm A n=52 Participants Commercially available normal saline will be used as the placebo. No active placebo drug will be mixed with the normal saline. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Placebo: Normal saline	Experimental Arm B n=55 Participants Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Pembrolizumab: Pembrolizumab, 200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or for up to 24 months
Number of Subjects With Adverse Events as a Measure of the Safety and Tolerability of Pembrolizumab	38 percentage of participants	59 percentage of participants

SECONDARY outcome

Timeframe: Response assessed every 12 weeks from the date of randomization to the date of documented disease progression or date of death, whichever occurs first, assessed for up to a maximum of 104 weeks (24 months)

Population: Only subjects with measureable disease per RECIST 1.1 at baseline were considered assessable for this endpoint. 10 subjects on Arm A and 12 subjects on Arm B were enrolled on the study with a complete response to previous therapy at baseline. One patient randomly assigned to placebo was excluded from the analysis because of inconsistent receipt of pembrolizumab rather than placebo during the initial several cycles of study treatment.

The objective response rate is the percentage of all subjects with confirmed PR or CR according to RECIST, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment)

Complete Response per RECIST 1.1 is defined as the disappearance of all target and non-target lesions and the reduction in size of any pathologic lymph nodes to <10mm in the absence of the appearance of any new lesions.

Partial Response per RECIST 1.1 is defined by at least a 30% decrease in the sum of the diameters of target lesions when compared to baseline, no equivocal progression of non-target disease and no appearance of new lesions.

Outcome measures

Measure	Control Arm A n=42 Participants Commercially available normal saline will be used as the placebo. No active placebo drug will be mixed with the normal saline. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Placebo: Normal saline	Experimental Arm B n=43 Participants Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Pembrolizumab: Pembrolizumab, 200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or for up to 24 months
Objective Response Rate (ORR) Assessment of Subjects on Maintenance Pembrolizumab vs Placebo	10 percentage of participants	23 percentage of participants

SECONDARY outcome

Timeframe: Every 12 weeks from the first treatment on the crossover to the date of documented disease progression, per irRECIST 1.1, assessed for up to a maximum of 104 weeks (24 months)

The objective response rate is the percentage of all subjects with confirmed PR or CR according to RECIST, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment)

Complete Response per RECIST 1.1 is defined as the disappearance of all target and non-target lesions and the reduction in size of any pathologic lymph nodes to <10mm in the absence of the appearance of any new lesions.

Partial Response per RECIST 1.1 is defined by at least a 30% decrease in the sum of the diameters of target lesions when compared to baseline, no equivocal progression of non-target disease and no appearance of new lesions.

Outcome measures

Measure	Control Arm A n=27 Participants Commercially available normal saline will be used as the placebo. No active placebo drug will be mixed with the normal saline. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Placebo: Normal saline	Experimental Arm B Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Pembrolizumab: Pembrolizumab, 200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or for up to 24 months
ORR Assessment of Subjects Receiving Pembrolizumab After Progressing on Placebo	22 percentage of participants	—

SECONDARY outcome

Timeframe: From randomization until death from any cause. Reported after a median follow-up of 12.9 months.

Population: One patient randomly assigned to placebo was excluded from the analysis because of inconsistent receipt of pembrolizumab rather than placebo during the initial several cycles of study treatment.

Median time from randomization until death from any cause in subjects treated with pembrolizumab vs placebo.

Outcome measures

Measure	Control Arm A n=52 Participants Commercially available normal saline will be used as the placebo. No active placebo drug will be mixed with the normal saline. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Placebo: Normal saline	Experimental Arm B n=55 Participants Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Pembrolizumab: Pembrolizumab, 200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or for up to 24 months
Median Overall Survival (OS) Time in Subjects Treated With Pembrolizumab vs Placebo	18.7 months Interval 11.4 to upper limit has not been achieved due to insufficient number of participants with events.	22 months Interval 12.9 to upper limit has not been achieved due to insufficient number of participants with events.

Adverse Events

Arm A

Serious events: 10 serious events

Other events: 50 other events

Deaths: 12 deaths

Arm B

Serious events: 25 serious events

Other events: 51 other events

Deaths: 24 deaths

Crossover

Serious events: 6 serious events

Other events: 24 other events

Deaths: 14 deaths

Serious adverse events

Measure	Arm A n=53 participants at risk Commercially available normal saline will be used as the placebo. No active placebo drug will be mixed with the normal saline. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Placebo: Normal saline	Arm B n=55 participants at risk Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Pembrolizumab: Pembrolizumab, 200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or for up to 24 months	Crossover n=27 participants at risk Arm A subjects that experienced progressive disease per RECIST 1.1 and opted to participate in the crossover portion of the trial. Subjects received pembrolizumab (200mg) every 3 weeks for up to 24 months.
Gastrointestinal disorders ABDOMINAL PAIN	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders CONSTIPATION	1.9% 1/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders DUODENAL OBSTRUCTION	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders DYSPNEA	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders GASTRIC HEMORRHAGE	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders GASTROINTESTINAL DISORDERS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Vascular disorders HEMATOMA	1.9% 1/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders STROKE	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Surgical and medical procedures SURGICAL AND MEDICAL PROCEDURES	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Vascular disorders THROMBOEMBOLIC EVENT	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders VOMITING	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Injury, poisoning and procedural complications WOUND COMPLICATION	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders ACUTE KIDNEY INJURY	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders ADULT RESPIRATORY DISTRESS SYNDROME	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations ALANINE AMINOTRANSFERASE INCREASED	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Blood and lymphatic system disorders ANEMIA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders ANOREXIA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Immune system disorders AUTOIMMUNE DISORDER	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Cardiac disorders CARDIAC DISORDERS - OTHER, SPECIFY	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders COLONIC OBSTRUCTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Psychiatric disorders CONFUSION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations CREATININE INCREASED	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders EDEMA LIMBS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders ENCEPHALOPATHY	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders FATIGUE	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders FEVER	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Musculoskeletal and connective tissue disorders FLANK PAIN	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Hepatobiliary disorders HEPATOBILIARY DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPERGLYCEMIA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPOKALEMIA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPONATREMIA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations INFECTIONS AND INFESTATIONS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations LUNG INFECTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders MULTI-ORGAN FAILURE	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Cardiac disorders MYOCARDIAL INFARCTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders NERVOUS SYSTEM DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders PAIN	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Reproductive system and breast disorders PELVIC PAIN	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations SEPSIS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders SMALL INTESTINAL OBSTRUCTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Injury, poisoning and procedural complications SPINAL FRACTURE	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders STOMACH PAIN	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders URINARY RETENTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations URINARY TRACT INFECTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders URINARY TRACT OBSTRUCTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Vascular disorders VASCULAR DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Cardiac disorders CARDIAC ARREST	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.

Other adverse events

Measure	Arm A n=53 participants at risk Commercially available normal saline will be used as the placebo. No active placebo drug will be mixed with the normal saline. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Placebo: Normal saline	Arm B n=55 participants at risk Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months. Pembrolizumab: Pembrolizumab, 200mg IV every 3 weeks until progressive disease, unacceptable toxicity, or for up to 24 months	Crossover n=27 participants at risk Arm A subjects that experienced progressive disease per RECIST 1.1 and opted to participate in the crossover portion of the trial. Subjects received pembrolizumab (200mg) every 3 weeks for up to 24 months.
Gastrointestinal disorders ABDOMINAL PAIN	15.1% 8/53 • Number of events 10 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.3% 4/55 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	14.8% 4/27 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Psychiatric disorders AGITATION	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations ALANINE AMINOTRANSFERASE INCREASED	1.9% 1/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	18.2% 10/55 • Number of events 17 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations ALKALINE PHOSPHATASE INCREASED	15.1% 8/53 • Number of events 12 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	21.8% 12/55 • Number of events 18 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	11.1% 3/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders ALLERGIC RHINITIS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders ALOPECIA	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders ANAL PAIN	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Blood and lymphatic system disorders ANEMIA	35.8% 19/53 • Number of events 34 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	30.9% 17/55 • Number of events 42 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	25.9% 7/27 • Number of events 17 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders ANOREXIA	13.2% 7/53 • Number of events 7 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	16.4% 9/55 • Number of events 10 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	18.5% 5/27 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Musculoskeletal and connective tissue disorders ARTHRALGIA	15.1% 8/53 • Number of events 10 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders ASCITES	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	7.5% 4/53 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	21.8% 12/55 • Number of events 21 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders ATELECTASIS	1.9% 1/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Musculoskeletal and connective tissue disorders BACK PAIN	5.7% 3/53 • Number of events 8 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	16.4% 9/55 • Number of events 10 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations BLADDER INFECTION	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations BLOOD BILIRUBIN INCREASED	5.7% 3/53 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Eye disorders BLURRED VISION	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	10.9% 6/55 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations BRONCHIAL INFECTION	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Injury, poisoning and procedural complications BRUISING	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders CHILLS	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	9.1% 5/55 • Number of events 9 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations CHOLESTEROL HIGH	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders CHRONIC KIDNEY DISEASE	3.8% 2/53 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders COLITIS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Psychiatric disorders CONFUSION	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders CONSTIPATION	20.8% 11/53 • Number of events 12 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	23.6% 13/55 • Number of events 19 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	11.1% 3/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders COUGH	15.1% 8/53 • Number of events 10 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	27.3% 15/55 • Number of events 15 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	25.9% 7/27 • Number of events 18 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations CREATININE INCREASED	24.5% 13/53 • Number of events 23 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	29.1% 16/55 • Number of events 40 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	18.5% 5/27 • Number of events 10 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders DEHYDRATION	7.5% 4/53 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Psychiatric disorders DELIRIUM	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Psychiatric disorders DEPRESSION	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders DIARRHEA	18.9% 10/53 • Number of events 11 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	36.4% 20/55 • Number of events 32 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	18.5% 5/27 • Number of events 7 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders DIZZINESS	17.0% 9/53 • Number of events 10 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	12.7% 7/55 • Number of events 8 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Eye disorders DRY EYE	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders DRY SKIN	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders DYSGEUSIA	5.7% 3/53 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders DYSPEPSIA	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders DYSPNEA	9.4% 5/53 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	25.5% 14/55 • Number of events 16 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	18.5% 5/27 • Number of events 7 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders EDEMA FACE	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders EDEMA LIMBS	9.4% 5/53 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	16.4% 9/55 • Number of events 10 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	11.1% 3/27 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Reproductive system and breast disorders ERECTILE DYSFUNCTION	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders ESOPHAGITIS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Eye disorders EYE DISORDERS	1.9% 1/53 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Eye disorders EYE PAIN	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Injury, poisoning and procedural complications FALL	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders FATIGUE	37.7% 20/53 • Number of events 29 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	38.2% 21/55 • Number of events 34 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	25.9% 7/27 • Number of events 11 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders FEVER	11.3% 6/53 • Number of events 7 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	9.1% 5/55 • Number of events 7 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	11.1% 3/27 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Musculoskeletal and connective tissue disorders FLANK PAIN	5.7% 3/53 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	9.1% 5/55 • Number of events 13 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders FLATULENCE	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Eye disorders FLOATERS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders GASTROESOPHAGEAL REFLUX DISEASE	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.3% 4/55 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders GASTROINTESTINAL DISORDERS	5.7% 3/53 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders GASTROPARESIS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS	1.9% 1/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	14.8% 4/27 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Musculoskeletal and connective tissue disorders GENERALIZED MUSCLE WEAKNESS	5.7% 3/53 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	9.1% 5/55 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders HEADACHE	9.4% 5/53 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	10.9% 6/55 • Number of events 10 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	11.1% 3/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Ear and labyrinth disorders HEARING IMPAIRED	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Cardiac disorders HEART FAILURE	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Vascular disorders HEMATOMA	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders HEMATURIA	17.0% 9/53 • Number of events 14 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	16.4% 9/55 • Number of events 18 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders HEMORRHOIDS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPERCALCEMIA	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.3% 4/55 • Number of events 7 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPERGLYCEMIA	15.1% 8/53 • Number of events 20 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	20.0% 11/55 • Number of events 64 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	25.9% 7/27 • Number of events 12 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders HYPERHIDROSIS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPERKALEMIA	9.4% 5/53 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	9.1% 5/55 • Number of events 9 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPERNATREMIA	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Vascular disorders HYPERTENSION	20.8% 11/53 • Number of events 15 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	16.4% 9/55 • Number of events 20 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	18.5% 5/27 • Number of events 8 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPOALBUMINEMIA	11.3% 6/53 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	10.9% 6/55 • Number of events 12 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	18.5% 5/27 • Number of events 11 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPOKALEMIA	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPOMAGNESEMIA	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	9.1% 5/55 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPONATREMIA	11.3% 6/53 • Number of events 8 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	16.4% 9/55 • Number of events 20 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Vascular disorders HYPOTENSION	1.9% 1/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Endocrine disorders HYPOTHYROIDISM	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	9.1% 5/55 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders HYPOXIA	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Psychiatric disorders INSOMNIA	5.7% 3/53 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	20.0% 11/55 • Number of events 12 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders IRRITABILITY	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Musculoskeletal and connective tissue disorders JOINT RANGE OF MOTION DECREASED	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Blood and lymphatic system disorders LEUKOCYTOSIS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders LOCALIZED EDEMA	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations LYMPHOCYTE COUNT DECREASED	15.1% 8/53 • Number of events 18 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	30.9% 17/55 • Number of events 35 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders MEMORY IMPAIRMENT	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders MUCOSITIS ORAL	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Musculoskeletal and connective tissue disorders MUSCLE WEAKNESS LOWER LIMB	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.3% 4/55 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Musculoskeletal and connective tissue disorders MYALGIA	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	9.1% 5/55 • Number of events 7 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.3% 4/55 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	11.1% 3/27 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders NAUSEA	18.9% 10/53 • Number of events 10 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	16.4% 9/55 • Number of events 15 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	14.8% 4/27 • Number of events 9 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Musculoskeletal and connective tissue disorders NECK PAIN	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.3% 4/55 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders NERVOUS SYSTEM DISORDERS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations NEUTROPHIL COUNT DECREASED	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 8 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders ORAL DYSESTHESIA	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders PAIN	11.3% 6/53 • Number of events 9 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	10.9% 6/55 • Number of events 7 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	11.3% 6/53 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	16.4% 9/55 • Number of events 14 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	11.1% 3/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders PARESTHESIA	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.3% 4/55 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations PARONYCHIA	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Reproductive system and breast disorders PELVIC PAIN	5.7% 3/53 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.3% 4/55 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders PERIPHERAL MOTOR NEUROPATHY	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders PERIPHERAL SENSORY NEUROPATHY	11.3% 6/53 • Number of events 8 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	16.4% 9/55 • Number of events 9 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations PLATELET COUNT DECREASED	13.2% 7/53 • Number of events 8 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	12.7% 7/55 • Number of events 11 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Hepatobiliary disorders PORTAL VEIN THROMBOSIS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders POSTNASAL DRIP	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders PRODUCTIVE COUGH	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	11.1% 3/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Injury, poisoning and procedural complications PROLAPSE OF INTESTINAL STOMA	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders PROTEINURIA	5.7% 3/53 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders PRURITUS	13.2% 7/53 • Number of events 7 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	23.6% 13/55 • Number of events 19 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders PULMONARY HYPERTENSION	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders RASH ACNEIFORM	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders RASH MACULO-PAPULAR	7.5% 4/53 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	21.8% 12/55 • Number of events 24 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders RENAL AND URINARY DISORDERS	5.7% 3/53 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Cardiac disorders RIGHT VENTRICULAR DYSFUNCTION	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations SEPSIS	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Cardiac disorders SINUS TACHYCARDIA	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations SINUSITIS	5.7% 3/53 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders SKIN AND SUBCUTANEOUS TISSUE DISORDERS	7.5% 4/53 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	10.9% 6/55 • Number of events 13 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations SKIN INFECTION	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders SORE THROAT	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Vascular disorders THROMBOEMBOLIC EVENT	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Ear and labyrinth disorders TINNITUS	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders TOOTHACHE	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations UPPER RESPIRATORY INFECTION	9.4% 5/53 • Number of events 7 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders URINARY FREQUENCY	5.7% 3/53 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders URINARY RETENTION	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations URINARY TRACT INFECTION	9.4% 5/53 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	18.2% 10/55 • Number of events 13 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders URINARY TRACT OBSTRUCTION	3.8% 2/53 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders URINARY TRACT PAIN	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders VOMITING	3.8% 2/53 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	16.4% 9/55 • Number of events 18 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations WEIGHT GAIN	1.9% 1/53 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations WEIGHT LOSS	3.8% 2/53 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	11.1% 3/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations WHITE BLOOD CELL DECREASED	3.8% 2/53 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	9.1% 5/55 • Number of events 13 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders ABDOMINAL DISTENSION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders ACUTE KIDNEY INJURY	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Endocrine disorders ADRENAL INSUFFICIENCY	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Psychiatric disorders ANXIETY	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.3% 4/55 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders BLADDER SPASM	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders BLOATING	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Blood and lymphatic system disorders BLOOD AND LYMPHATIC SYSTEM DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders BULLOUS DERMATITIS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Cardiac disorders CARDIAC DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Cardiac disorders CHEST PAIN - CARDIAC	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders DENTAL CARIES	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders DRY MOUTH	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	10.9% 6/55 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders DUODENAL ULCER	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders DYSPHAGIA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Ear and labyrinth disorders EAR AND LABYRINTH DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders ENCEPHALOPATHY	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Endocrine disorders ENDOCRINE DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders ESOPHAGEAL ULCER	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders FECAL INCONTINENCE	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders FLU LIKE SYMPTOMS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	7.4% 2/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders GAIT DISTURBANCE	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Hepatobiliary disorders GALLBLADDER PAIN	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders GASTRITIS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Reproductive system and breast disorders GENITAL EDEMA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations GGT INCREASED	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations HEMOGLOBIN INCREASED	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Hepatobiliary disorders HEPATOBILIARY DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Vascular disorders HOT FLASHES	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Endocrine disorders HYPERTHYROIDISM	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	9.1% 5/55 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPERURICEMIA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPOCALCEMIA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPOGLYCEMIA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPOPHOSPHATEMIA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Immune system disorders IMMUNE SYSTEM DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 4 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations INFECTIONS AND INFESTATIONS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Injury, poisoning and procedural complications INJURY, POISONING AND PROCEDURAL COMPLICATIONS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations INR INCREASED	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations KIDNEY INFECTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders LETHARGY	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations LIP INFECTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations LIPASE INCREASED	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 6 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations LUNG INFECTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders MOVEMENTS INVOLUNTARY	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders NAIL DISCOLORATION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations NAIL INFECTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders NAIL RIDGING	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders NECK EDEMA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
General disorders NON-CARDIAC CHEST PAIN	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders PANCREATITIS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations PENILE INFECTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Reproductive system and breast disorders PENILE PAIN	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations PHARYNGITIS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders PHOTOSENSITIVITY	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Reproductive system and breast disorders PROSTATIC PAIN	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations RASH PUSTULAR	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Reproductive system and breast disorders REPRODUCTIVE SYSTEM AND BREAST DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Investigations SERUM AMYLASE INCREASED	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders SKIN HYPOPIGMENTATION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders SKIN INDURATION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders SKIN ULCERATION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Nervous system disorders SYNCOPE	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Reproductive system and breast disorders TESTICULAR PAIN	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Blood and lymphatic system disorders THROMBOTIC THROMBOCYTOPENIC PURPURA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Infections and infestations TOOTH INFECTION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.6% 2/55 • Number of events 2 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders URINARY INCONTINENCE	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	9.1% 5/55 • Number of events 5 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Renal and urinary disorders URINARY URGENCY	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	5.5% 3/55 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Vascular disorders VASCULAR DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Eye disorders WATERING EYES	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders WHEEZING	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	1.8% 1/55 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/27 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Cardiac disorders ATRIAL FLUTTER	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders ERYTHEMA MULTIFORME	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Injury, poisoning and procedural complications FRACTURE	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders HOARSENESS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Metabolism and nutrition disorders HYPERTRIGLYCERIDEMIA	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Musculoskeletal and connective tissue disorders MYOSITIS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 3 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Gastrointestinal disorders RECTAL HEMORRHAGE	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Respiratory, thoracic and mediastinal disorders RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.
Skin and subcutaneous tissue disorders SKIN HYPERPIGMENTATION	0.00% 0/53 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	0.00% 0/55 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.	3.7% 1/27 • Number of events 1 • Adverse Events were recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) up to 25 months.

Additional Information

Clinical Trials Results Coordinator

Hoosier Cancer Research Network

Phone: 317-634-5842

Email: aneal@hoosiercancer.org

Results disclosure agreements

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