Trial Outcomes & Findings for Long Term Safety of Immediate-release Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (NCT NCT02251275)

NCT ID: NCT02251275

Last Updated: 2019-11-27

Results Overview

An adverse event (AE) was as any untoward medical occurrence associated with the use of an investigational medicinal product (IMP), whether or not considered IMP related. A TEAE was an AE that started after trial drug treatment; or if the event was continuous from baseline and was serious, related to IMP, or resulted in death, discontinuation, interruption or reduction of trial therapy. A serious TEAE included any event that resulted in: death, life-threatening, persistent or significant incapacity, substantial disruption of ability to conduct normal life functions, required inpatient hospitalization, prolonged hospitalization, congenital anomaly/birth defect, or other medically significant events as per medical judgment, that jeopardized the participant and that required medical or surgical intervention. A severe TEAE was an inability to work or perform normal daily activity. A summary of serious and all other non-serious TEAEs, regardless of causality, is located in the AE section.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1803 participants
• Primary outcome timeframe: Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment(+ 7 days)
• Results posted on: 2019-11-27

Participant Flow

Eligible participants could enroll into Trial 156-13-211 after completing follow-up visit(s) of their previous trial (156-13-210, 156-08-271, 156-04-251, or 156-09-290).

One participant screened, but withdrew consent on the same day (prior to study drug treatment) and is not included in the study data. Starting doses depended on the participant's previous trial.

Participant milestones

Measure	Tolvaptan (From 156-13-210: Tolvaptan) Participants were previously treated with tolvaptan in Trial 156-13-210. Participants initiated on tolvaptan at a split-dose of 45/15 milligrams (mg) with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From 156-13-210: Placebo) Participants were previously treated with placebo in Trial 156-13-210. Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From 156-08-271: Tolvaptan) Participants were previously treated with tolvaptan in Trial 156-08-271. Participants retained the last dose level of tolvaptan received in the trial (45/15 mg, 60/30 mg, or 90/30 mg) and started at that same dose in Trial 156-13-211.	Tolvaptan (From Other: Tolvaptan) Participants were previously treated with tolvaptan in Other Trials (156-04-251 and 156-09-290). Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From Other: Placebo) Participants were previously treated with placebo in Other Trials (156-04-251 and 156-09-290). Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.
Overall Study STARTED	506	570	718	6	3
Overall Study Received at Least 1 Dose of Study Drug	505	569	717	6	3
Overall Study COMPLETED	434	423	624	5	2
Overall Study NOT COMPLETED	72	147	94	1	1

Reasons for withdrawal

Measure	Tolvaptan (From 156-13-210: Tolvaptan) Participants were previously treated with tolvaptan in Trial 156-13-210. Participants initiated on tolvaptan at a split-dose of 45/15 milligrams (mg) with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From 156-13-210: Placebo) Participants were previously treated with placebo in Trial 156-13-210. Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From 156-08-271: Tolvaptan) Participants were previously treated with tolvaptan in Trial 156-08-271. Participants retained the last dose level of tolvaptan received in the trial (45/15 mg, 60/30 mg, or 90/30 mg) and started at that same dose in Trial 156-13-211.	Tolvaptan (From Other: Tolvaptan) Participants were previously treated with tolvaptan in Other Trials (156-04-251 and 156-09-290). Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From Other: Placebo) Participants were previously treated with placebo in Other Trials (156-04-251 and 156-09-290). Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.
Overall Study Adverse Event	23	60	28	0	0
Overall Study Lost to Follow-up	5	6	4	0	0
Overall Study Physician Decision	19	30	26	0	1
Overall Study Protocol Deviation	0	0	1	0	0
Overall Study Withdrawal by Subject	25	51	35	1	0

Baseline Characteristics

Long Term Safety of Immediate-release Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease

Baseline characteristics by cohort

Measure	Tolvaptan (From 156-13-210: Tolvaptan) n=506 Participants Participants were previously treated with tolvaptan in Trial 156-13-210. Participants initiated on tolvaptan at a split-dose of 45/15 milligrams (mg) with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From 156-13-210: Placebo) n=570 Participants Participants were previously treated with placebo in Trial 156-13-210. Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From 156-08-271: Tolvaptan) n=718 Participants Participants were previously treated with tolvaptan in Trial 156-08-271. Participants retained the last dose level of tolvaptan received in the trial (45/15 mg, 60/30 mg, or 90/30 mg) and started at that same dose in Trial 156-13-211.	Tolvaptan (From Other: Tolvaptan) n=6 Participants Participants were previously treated with tolvaptan in Other Trials (156-04-251 and 156-09-290). Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From Other: Placebo) n=3 Participants Participants were previously treated with placebo in Other Trials (156-04-251 and 156-09-290). Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Total n=1803 Participants Total of all reporting groups
Age, Continuous	48.9 Years STANDARD_DEVIATION 8.1 • n=5 Participants	48.6 Years STANDARD_DEVIATION 8.0 • n=7 Participants	45.5 Years STANDARD_DEVIATION 7.8 • n=5 Participants	41.2 Years STANDARD_DEVIATION 11.4 • n=4 Participants	47.0 Years STANDARD_DEVIATION 2.6 • n=21 Participants	47.4 Years STANDARD_DEVIATION 8.1 • n=10 Participants
Sex: Female, Male Female	234 Participants n=5 Participants	290 Participants n=7 Participants	343 Participants n=5 Participants	5 Participants n=4 Participants	2 Participants n=21 Participants	874 Participants n=10 Participants
Sex: Female, Male Male	272 Participants n=5 Participants	280 Participants n=7 Participants	375 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	929 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	27 Participants n=5 Participants	25 Participants n=7 Participants	49 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	102 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	479 Participants n=5 Participants	545 Participants n=7 Participants	669 Participants n=5 Participants	5 Participants n=4 Participants	3 Participants n=21 Participants	1701 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=10 Participants
Race (NIH/OMB) Asian	16 Participants n=5 Participants	16 Participants n=7 Participants	10 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	42 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=10 Participants
Race (NIH/OMB) Black or African American	19 Participants n=5 Participants	23 Participants n=7 Participants	6 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	48 Participants n=10 Participants
Race (NIH/OMB) White	461 Participants n=5 Participants	525 Participants n=7 Participants	694 Participants n=5 Participants	6 Participants n=4 Participants	3 Participants n=21 Participants	1689 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	18 Participants n=10 Participants

PRIMARY outcome

Timeframe: Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment(+ 7 days)

Population: All participants who received at least 1 dose of study drug.

An adverse event (AE) was as any untoward medical occurrence associated with the use of an investigational medicinal product (IMP), whether or not considered IMP related. A TEAE was an AE that started after trial drug treatment; or if the event was continuous from baseline and was serious, related to IMP, or resulted in death, discontinuation, interruption or reduction of trial therapy. A serious TEAE included any event that resulted in: death, life-threatening, persistent or significant incapacity, substantial disruption of ability to conduct normal life functions, required inpatient hospitalization, prolonged hospitalization, congenital anomaly/birth defect, or other medically significant events as per medical judgment, that jeopardized the participant and that required medical or surgical intervention. A severe TEAE was an inability to work or perform normal daily activity. A summary of serious and all other non-serious TEAEs, regardless of causality, is located in the AE section.

Outcome measures

Measure	Tolvaptan (From 156-13-210: Tolvaptan) n=505 Participants Participants were previously treated with tolvaptan in Trial 156-13-210. Participants initiated on tolvaptan at a split-dose of 45/15 milligrams (mg) with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From 156-13-210: Placebo) n=569 Participants Participants were previously treated with placebo in Trial 156-13-210. Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From 156-08-271: Tolvaptan) n=717 Participants Participants were previously treated with tolvaptan in Trial 156-08-271. Participants retained the last dose level of tolvaptan received in the trial (45/15 mg, 60/30 mg, or 90/30 mg) and started at that same dose in Trial 156-13-211.	Tolvaptan (From Other: Tolvaptan) n=6 Participants Participants were previously treated with tolvaptan in Other Trials (156-04-251 and 156-09-290). Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From Other: Placebo) n=3 Participants Participants were previously treated with placebo in Other Trials (156-04-251 and 156-09-290). Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.
Number Of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) Discontinued due to TEAEs	33 participants	65 participants	38 participants	0 participants	1 participants
Number Of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) Participants with TEAEs	473 participants	531 participants	640 participants	6 participants	3 participants
Number Of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) Participants with serious TEAEs	87 participants	96 participants	103 participants	1 participants	2 participants
Number Of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) Deaths	1 participants	5 participants	3 participants	0 participants	0 participants
Number Of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) Participants with severe TEAEs	74 participants	78 participants	83 participants	2 participants	1 participants

Adverse Events

Tolvaptan (From 156-13-210: Tolvaptan)

Serious events: 87 serious events

Other events: 469 other events

Deaths: 1 deaths

Tolvaptan (From 156-13-210: Placebo)

Serious events: 96 serious events

Other events: 525 other events

Deaths: 5 deaths

Tolvaptan (From 156-08-271: Tolvaptan)

Serious events: 103 serious events

Other events: 633 other events

Deaths: 3 deaths

Tolvaptan (From Other: Tolvaptan)

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Tolvaptan (From Other: Placebo)

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tolvaptan (From 156-13-210: Tolvaptan) n=505 participants at risk Participants were previously treated with tolvaptan in Trial 156-13-210. Participants initiated on tolvaptan at a split-dose of 45/15 milligrams (mg) with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From 156-13-210: Placebo) n=569 participants at risk Participants were previously treated with placebo in Trial 156-13-210. Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From 156-08-271: Tolvaptan) n=717 participants at risk Participants were previously treated with tolvaptan in Trial 156-08-271. Participants retained the last dose level of tolvaptan received in the trial (45/15 mg, 60/30 mg, or 90/30 mg) and started at that same dose in Trial 156-13-211.	Tolvaptan (From Other: Tolvaptan) n=6 participants at risk Participants were previously treated with tolvaptan in Other Trials (156-04-251 and 156-09-290). Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From Other: Placebo) n=3 participants at risk Participants were previously treated with placebo in Other Trials (156-04-251 and 156-09-290). Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.
Cardiac disorders Cardiogenic Shock	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Cardiac Failure	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Cardiac Arrest	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Atrial Fibrillation	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.42% 3/717 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Aortic Valve Incompetence	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Angina Unstable	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Angina Pectoris	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.35% 2/569 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Acute Myocardial Infarction	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Acute Left Ventricular Failure	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Acute Coronary Syndrome	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Congenital, familial and genetic disorders Polycystic Liver Disease	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Congenital, familial and genetic disorders Urachal Abnormality	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Ear and labyrinth disorders Deafness	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Eye disorders Retinal Detachment	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.28% 2/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Eye disorders Borderline Glaucoma	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Eye disorders Diplopia	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Eye disorders Endocrine Ophthalmopathy	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Gastrointestinal Disorder	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Vomiting	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Upper Gastrointestinal Haemorrhage	0.20% 1/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Umbilical Hernia	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.42% 3/717 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Small Intestinal Obstruction	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Pancreatitis Acute	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Pancreatitis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Nausea	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Lower Gastrointestinal Haemorrhage	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Intestinal Obstruction	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Inguinal Hernia, Obstructive	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Inguinal Hernia	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Incarcerated Umbilical Hernia	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Ileus	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.42% 3/717 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Colitis Ischaemic	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Gastrooesophageal Reflux Disease	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Gastritis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Gastric Ulcer Haemorrhage	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Duodenal Perforation	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Diverticulum	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Diarrhoea	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.53% 3/569 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Constipation	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Haematemesis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Colitis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Ascites	0.20% 1/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Abdominal Pain Upper	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Abdominal Pain Lower	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Abdominal Pain	0.59% 3/505 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Abdominal Hernia	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Pyrexia	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Thirst	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Oedema Peripheral	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Chest Pain	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Fatigue	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Death	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Non-Cardiac Chest Pain	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.35% 2/569 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Asthenia	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Chest Discomfort	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Hepatobiliary disorders Bile Duct Stone	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Hepatobiliary disorders Cholecystitis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Hepatobiliary disorders Cholelithiasis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Hepatobiliary disorders Hepatic Cyst	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Hepatobiliary disorders Hepatic Pain	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Hepatobiliary disorders Ischaemic Hepatitis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Immune system disorders Drug Hypersensitivity	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Pulmonary Tuberculosis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Pyelonephritis	0.59% 3/505 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Postoperative Wound Infection	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Renal Abscess	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Renal Cyst Infection	0.99% 5/505 • Number of events 7 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.4% 8/569 • Number of events 10 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Salmonellosis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Sepsis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.35% 2/569 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.28% 2/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Urinary Tract Infection	0.59% 3/505 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.35% 2/569 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.70% 5/717 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Sinusitis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Staphylococcal Infection	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Superinfection	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Tonsillitis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Urosepsis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.28% 2/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Viral Infection	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Pneumonia Staphylococcal	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Septic Shock	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Pneumonia	0.79% 4/505 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.88% 5/569 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Abdominal Wall Abscess	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Ophthalmic Herpes Zoster	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Appendicitis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Appendicitis Perforated	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Cat Scratch Disease	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Cellulitis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Clostridium Difficile Infection	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Peritonitis Bacterial	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Diarrhoea Infectious	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Diverticulitis	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Cytomegalovirus	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Escherichia Bacteraemia	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Escherichia Urinary Tract Infection	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Gastroenteritis	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.53% 3/569 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Hepatic Cyst Infection	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Herpes Zoster	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Herpes Zoster Oticus	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Infected Cyst	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Infection	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Endocarditis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Radius Fracture	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.28% 2/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Tibia Fracture	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Tendon Rupture	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Subdural Haematoma	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Subarachnoid Haemorrhage	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Spinal Fracture	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Perirenal Haematoma	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Traumatic Haemothorax	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Injury	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Incisional Hernia	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Humerus Fracture	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Fibula Fracture	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Brain Contusion	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Arteriovenous Fistula Site Haematoma	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Ankle Fracture	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Anastomotic Complication	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Meniscus Injury	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Accidental Overdose	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.28% 2/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Weight Decreased	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Tumour Marker Increased	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Liver Function Test Increased	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.53% 3/569 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations International Normalised Ratio Fluctuation	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Hepatic Enzyme Increased	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.53% 3/569 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Glomerular Filtration Rate Decreased	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.53% 3/569 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Transaminases Increased	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations C-Reactive Protein Increased	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Gamma-Glutamyltransferase Increased	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.35% 2/569 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Alanine Aminotransferase Increased	0.59% 3/505 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.88% 5/569 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Aspartate Aminotransferase Increased	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Alanine Aminotransferase Abnormal	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Blood Creatinine Increased	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.88% 5/569 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.42% 3/717 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Blood Glucose Increased	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Blood Alkaline Phosphatase Increased	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Blood Urine Present	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Dehydration	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Diabetes Mellitus	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Hyperkalaemia	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Hypoglycaemia	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Hyponatraemia	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.35% 2/569 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Metabolic Acidosis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Obesity	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Musculoskeletal and connective tissue disorders Spinal Osteoarthritis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Musculoskeletal and connective tissue disorders Foot Deformity	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Musculoskeletal and connective tissue disorders Arthralgia	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Musculoskeletal and connective tissue disorders Pain In Extremity	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic Squamous Cell Carcinoma	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma of Head and Neck	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal Neoplasm	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal Cancer	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer	0.37% 1/272 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.36% 1/280 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/375 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary Thyroid Cancer	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian Theca Cell Tumour	0.00% 0/234 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.34% 1/290 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/343 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Meninges	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid Tumour	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Adrenals	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Liver	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal Cell Carcinoma	0.40% 2/505 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone Cancer Metastatic	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-Cell Small Lymphocytic Lymphoma	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal Proliferative Breast Lesion	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Melanoma	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchial Carcinoma	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Paraesthesia	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Tremor	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Transient Ischaemic Attack	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Syncope	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.35% 2/569 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Sciatica	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Ruptured Cerebral Aneurysm	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Presyncope	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Vith Nerve Paralysis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Headache	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Intracranial Aneurysm	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Basilar Artery Aneurysm	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Cerebellar Ischaemia	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Ischaemic Stroke	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Cerebrovascular Accident	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Encephalopathy	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Cerebral Ischaemia	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Epilepsy	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Psychiatric disorders Depression	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Psychiatric disorders Panic Attack	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Psychiatric disorders Suicidal Ideation	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Renal Pain	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.88% 5/569 • Number of events 7 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Renal Impairment	1.2% 6/505 • Number of events 6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.35% 2/569 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.42% 3/717 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Renal Haemorrhage	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Renal Failure	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.28% 2/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Renal Cyst Haemorrhage	0.59% 3/505 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.70% 4/569 • Number of events 6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Renal Cyst	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Renal Colic	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Renal Cyst Ruptured	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.28% 2/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Pollakiuria	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Nephropathy	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Acute Kidney Injury	0.99% 5/505 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.4% 8/569 • Number of events 9 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.98% 7/717 • Number of events 7 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Nephrolithiasis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Kidney Enlargement	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Haematuria	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.35% 2/569 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders End Stage Renal Disease	0.59% 3/505 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.1% 8/717 • Number of events 8 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Chronic Kidney Disease	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Polyuria	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Reproductive system and breast disorders Rectocele	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Reproductive system and breast disorders Prostatitis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Reproductive system and breast disorders Menorrhagia	0.43% 1/234 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/290 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/343 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Reproductive system and breast disorders Breast Enlargement	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Reproductive system and breast disorders Metrorrhagia	0.00% 0/234 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.34% 1/290 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/343 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Sinus Polyp	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Pleuritic Pain	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Pulmonary Toxicity	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.28% 2/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Acute Respiratory Distress Syndrome	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Acute Pulmonary Oedema	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Skin and subcutaneous tissue disorders Rash Vesicular	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Skin and subcutaneous tissue disorders Skin Laxity	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Skin and subcutaneous tissue disorders Skin Lesion	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Thrombophlebitis Superficial	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Shock	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Peripheral Ischaemia	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Hypotension	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.35% 2/569 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Hypertensive Crisis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Deep Vein Thrombosis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Haemorrhage	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Arteritis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Aortic Dissection	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Aneurysm	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Hypertension	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.42% 3/717 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Aortic Aneurysm	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Blood and lymphatic system disorders Anaemia	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.28% 2/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Blood and lymphatic system disorders Haemorrhagic Anaemia	0.20% 1/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Blood and lymphatic system disorders Leukocytosis	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Blood and lymphatic system disorders Pancytopenia	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Ventricular Tachycardia	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Pericarditis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Pericardial Effusion	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Myocardial Infarction	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Mitral Valve Prolapse	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Left Ventricular Dysfunction	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Coronary Artery Stenosis	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Coronary Artery Disease	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)

Other adverse events

Measure	Tolvaptan (From 156-13-210: Tolvaptan) n=505 participants at risk Participants were previously treated with tolvaptan in Trial 156-13-210. Participants initiated on tolvaptan at a split-dose of 45/15 milligrams (mg) with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From 156-13-210: Placebo) n=569 participants at risk Participants were previously treated with placebo in Trial 156-13-210. Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From 156-08-271: Tolvaptan) n=717 participants at risk Participants were previously treated with tolvaptan in Trial 156-08-271. Participants retained the last dose level of tolvaptan received in the trial (45/15 mg, 60/30 mg, or 90/30 mg) and started at that same dose in Trial 156-13-211.	Tolvaptan (From Other: Tolvaptan) n=6 participants at risk Participants were previously treated with tolvaptan in Other Trials (156-04-251 and 156-09-290). Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.	Tolvaptan (From Other: Placebo) n=3 participants at risk Participants were previously treated with placebo in Other Trials (156-04-251 and 156-09-290). Participants initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.
Respiratory, thoracic and mediastinal disorders Cough	5.3% 27/505 • Number of events 30 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	4.7% 27/569 • Number of events 31 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	3.9% 28/717 • Number of events 31 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Respiratory, thoracic and mediastinal disorders Wheezing	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Skin and subcutaneous tissue disorders Dermatitis Contact	1.4% 7/505 • Number of events 9 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.70% 4/569 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.42% 3/717 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Left Ventricular Hypertrophy	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Cardiac disorders Palpitations	0.99% 5/505 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.1% 6/569 • Number of events 6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	2.0% 14/717 • Number of events 15 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Ear and labyrinth disorders Hypoacusis	0.59% 3/505 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Ear and labyrinth disorders Motion Sickness	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Abdominal Discomfort	1.8% 9/505 • Number of events 10 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	2.5% 14/569 • Number of events 16 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.56% 4/717 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Abdominal Hernia	1.4% 7/505 • Number of events 7 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.84% 6/717 • Number of events 6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Abdominal Pain Lower	1.2% 6/505 • Number of events 6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.1% 6/569 • Number of events 7 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.84% 6/717 • Number of events 6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Abdominal Pain Upper	4.0% 20/505 • Number of events 24 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	3.3% 19/569 • Number of events 24 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.7% 12/717 • Number of events 12 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Constipation	3.2% 16/505 • Number of events 17 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	4.9% 28/569 • Number of events 34 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.4% 10/717 • Number of events 11 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Diarrhoea	7.3% 37/505 • Number of events 41 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	6.7% 38/569 • Number of events 43 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	4.6% 33/717 • Number of events 39 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Dry Mouth	4.4% 22/505 • Number of events 24 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	6.7% 38/569 • Number of events 41 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.42% 3/717 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Dyspepsia	3.4% 17/505 • Number of events 19 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	4.7% 27/569 • Number of events 28 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.4% 10/717 • Number of events 10 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Gastrooesophageal Reflux Disease	2.2% 11/505 • Number of events 11 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	3.3% 19/569 • Number of events 22 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	2.4% 17/717 • Number of events 17 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Gingival Pain	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Nausea	7.3% 37/505 • Number of events 40 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	9.0% 51/569 • Number of events 59 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	5.3% 38/717 • Number of events 40 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Gastrointestinal disorders Vomiting	4.8% 24/505 • Number of events 27 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	6.7% 38/569 • Number of events 41 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	4.5% 32/717 • Number of events 36 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Chest Discomfort	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Fatigue	9.3% 47/505 • Number of events 55 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	13.0% 74/569 • Number of events 85 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	4.7% 34/717 • Number of events 37 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Non-Cardiac Chest Pain	0.99% 5/505 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.88% 5/569 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.56% 4/717 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Oedema Peripheral	6.3% 32/505 • Number of events 37 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	6.9% 39/569 • Number of events 46 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	5.9% 42/717 • Number of events 49 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Pain	1.2% 6/505 • Number of events 9 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.42% 3/717 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
General disorders Thirst	27.5% 139/505 • Number of events 176 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	32.2% 183/569 • Number of events 213 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	12.7% 91/717 • Number of events 99 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	66.7% 4/6 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Immune system disorders Type I Hypersensitivity	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Bronchitis	4.6% 23/505 • Number of events 25 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	5.1% 29/569 • Number of events 34 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	4.3% 31/717 • Number of events 35 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Ear Infection	1.6% 8/505 • Number of events 9 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.6% 9/569 • Number of events 9 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.70% 5/717 • Number of events 8 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Gastroenteritis	2.8% 14/505 • Number of events 15 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	3.9% 22/569 • Number of events 24 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	5.7% 41/717 • Number of events 44 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Gingivitis	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.53% 3/569 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.28% 2/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Influenza	6.7% 34/505 • Number of events 38 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	7.6% 43/569 • Number of events 49 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	5.4% 39/717 • Number of events 52 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Nasopharyngitis	18.2% 92/505 • Number of events 129 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	17.6% 100/569 • Number of events 143 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	13.1% 94/717 • Number of events 123 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Sinusitis	4.4% 22/505 • Number of events 30 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	5.4% 31/569 • Number of events 37 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	4.9% 35/717 • Number of events 47 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Upper Respiratory Tract Infection	11.5% 58/505 • Number of events 64 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	9.3% 53/569 • Number of events 83 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	12.0% 86/717 • Number of events 129 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Urinary Tract Infection	10.3% 52/505 • Number of events 86 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	10.2% 58/569 • Number of events 79 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	9.1% 65/717 • Number of events 117 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Vulvovaginal Mycotic Infection	1.3% 3/234 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.34% 1/290 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.7% 6/343 • Number of events 7 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	50.0% 1/2 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Infections and infestations Zika Virus Infection	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Injury, poisoning and procedural complications Fall	1.6% 8/505 • Number of events 10 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.6% 9/569 • Number of events 10 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.5% 11/717 • Number of events 11 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Alanine Aminotransferase Increased	1.4% 7/505 • Number of events 9 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	3.3% 19/569 • Number of events 26 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	2.4% 17/717 • Number of events 21 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Blood Calcium Increased	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Blood Creatinine Increased	15.2% 77/505 • Number of events 104 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	15.3% 87/569 • Number of events 129 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	9.6% 69/717 • Number of events 87 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Kidney Palpable	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Weight Decreased	0.79% 4/505 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.88% 5/569 • Number of events 6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.28% 2/717 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Investigations Weight Increased	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.53% 3/569 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.56% 4/717 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Decreased Appetite	1.6% 8/505 • Number of events 9 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	3.2% 18/569 • Number of events 19 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.56% 4/717 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Gout	5.5% 28/505 • Number of events 49 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	4.4% 25/569 • Number of events 46 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	4.2% 30/717 • Number of events 42 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Hyperlipidaemia	0.79% 4/505 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.88% 5/569 • Number of events 5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.98% 7/717 • Number of events 7 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Metabolism and nutrition disorders Polydipsia	5.3% 27/505 • Number of events 29 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	9.3% 53/569 • Number of events 54 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	2.0% 14/717 • Number of events 14 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Musculoskeletal and connective tissue disorders Arthralgia	6.5% 33/505 • Number of events 42 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	4.4% 25/569 • Number of events 26 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	3.6% 26/717 • Number of events 36 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Musculoskeletal and connective tissue disorders Back Pain	10.5% 53/505 • Number of events 59 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	10.0% 57/569 • Number of events 71 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	7.1% 51/717 • Number of events 55 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Dizziness	3.6% 18/505 • Number of events 20 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	5.4% 31/569 • Number of events 37 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	4.3% 31/717 • Number of events 37 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Headache	10.1% 51/505 • Number of events 61 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	12.7% 72/569 • Number of events 83 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	7.1% 51/717 • Number of events 68 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 2/6 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Nervous system disorders Tremor	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.18% 1/569 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.28% 2/717 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Psychiatric disorders Anxiety	1.8% 9/505 • Number of events 9 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.6% 9/569 • Number of events 9 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.8% 13/717 • Number of events 15 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Psychiatric disorders Stress	0.40% 2/505 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.70% 4/569 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.14% 1/717 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Chronic Kidney Disease	0.79% 4/505 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.1% 6/569 • Number of events 6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.98% 7/717 • Number of events 7 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Haematuria	5.3% 27/505 • Number of events 34 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	9.1% 52/569 • Number of events 63 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	6.7% 48/717 • Number of events 53 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	66.7% 2/3 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Nocturia	15.2% 77/505 • Number of events 105 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	21.8% 124/569 • Number of events 150 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	8.1% 58/717 • Number of events 63 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	50.0% 3/6 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Pollakiuria	5.3% 27/505 • Number of events 36 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	6.0% 34/569 • Number of events 38 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.7% 12/717 • Number of events 18 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 2/6 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Polyuria	23.2% 117/505 • Number of events 141 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	31.6% 180/569 • Number of events 203 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	7.4% 53/717 • Number of events 56 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 2/6 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Renal Cyst Ruptured	0.79% 4/505 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	1.6% 9/569 • Number of events 12 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.98% 7/717 • Number of events 8 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Renal Impairment	2.4% 12/505 • Number of events 12 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	5.1% 29/569 • Number of events 31 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	2.0% 14/717 • Number of events 16 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Renal and urinary disorders Renal Pain	19.4% 98/505 • Number of events 139 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	19.3% 110/569 • Number of events 179 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	19.7% 141/717 • Number of events 209 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	50.0% 3/6 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	66.7% 2/3 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Reproductive system and breast disorders Vaginal Haemorrhage	0.00% 0/234 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.34% 1/290 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.87% 3/343 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/5 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	50.0% 1/2 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Hypertension	17.2% 87/505 • Number of events 116 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	13.5% 77/569 • Number of events 97 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	19.4% 139/717 • Number of events 163 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	66.7% 4/6 • Number of events 4 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Lymphoedema	0.00% 0/505 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/569 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/717 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/6 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	33.3% 1/3 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)
Vascular disorders Orthostatic Hypotension	0.20% 1/505 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.35% 2/569 • Number of events 2 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.42% 3/717 • Number of events 3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	16.7% 1/6 • Number of events 1 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)	0.00% 0/3 • Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days)

Additional Information

Global Clinical Development

Otsuka Pharmaceutical Development & Commercialization, Inc.

Phone: +1-609-524-6788

Email: clinicaltransparency@otsuka-us.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.
• Publication restrictions are in place

Restriction type: OTHER