Trial Outcomes & Findings for INC424 for Patients With Primary Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis. (NCT NCT01493414)

Last Updated: 2019-04-26

Results Overview

An adverse event (AE) is any untoward medical occurrence in a clinical trial participant regardless of causal relationship to study drug and regardless whether study drug has been administered. A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. A non-serious AE is any AE that does not meet the criteria above.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2233 participants

Primary outcome timeframe

Baseline up to approximately 5 years

Results posted on

2019-04-26

Participant Flow

This was an expanded access study intended to provide an access path to ruxolitinib for patients with Myelofibrosis (MF) and to allow for collection of additional safety and efficacy data for ruxolitinib.

Participant milestones

Participant milestones
Measure	INC424 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Overall Study STARTED	2233
Overall Study COMPLETED	1283
Overall Study NOT COMPLETED	950

Reasons for withdrawal

Reasons for withdrawal
Measure	INC424 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Overall Study Adverse Event	405
Overall Study Disease progression	204
Overall Study Death	101
Overall Study Physician Decision	93
Overall Study Withdrawal by Subject	79
Overall Study Protocol deviation	27
Overall Study Administrative problems	25
Overall Study Lost to Follow-up	16

Baseline Characteristics

INC424 for Patients With Primary Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	INC424 n=2233 Participants 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Age, Continuous	65.6 years STANDARD_DEVIATION 10.50 • n=99 Participants
Sex: Female, Male Female	1016 Participants n=99 Participants
Sex: Female, Male Male	1217 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	6 Participants n=99 Participants
Race (NIH/OMB) Asian	23 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=99 Participants
Race (NIH/OMB) Black or African American	20 Participants n=99 Participants
Race (NIH/OMB) White	2087 Participants n=99 Participants
Race (NIH/OMB) More than one race	96 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race/Ethnicity, Customized Hispanic/Latino	509 Participants n=99 Participants
Race/Ethnicity, Customized Chinese	1 Participants n=99 Participants
Race/Ethnicity, Customized Indian (Indian subcontinent)	1 Participants n=99 Participants
Race/Ethnicity, Customized Japanese	0 Participants n=99 Participants
Race/Ethnicity, Customized Mixed Ethnicity	15 Participants n=99 Participants
Race/Ethnicity, Customized Others	1707 Participants n=99 Participants
ECOG score 0	1061 Participants n=99 Participants
ECOG score 1	960 Participants n=99 Participants
ECOG score 2	197 Participants n=99 Participants
ECOG score 3	1 Participants n=99 Participants
ECOG score 4	0 Participants n=99 Participants
ECOG score Missing	14 Participants n=99 Participants

PRIMARY outcome

Timeframe: Baseline up to approximately 5 years

Population: Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.

Outcome measures

Outcome measures
Measure	INC424 n=2233 Participants 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Stable Disease Participants with Stable Disease with spleen length between 5 and 10 cm=does not meet criteria for response or disease progression. Participants with Stable Disease with spleen length more than 10 cm=does not meet criteria for response or disease progression. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Progressive Disease Participants with Progressive Disease with spleen length between 5 and 10 cm=increase of 100% from baseline in spleen length. Participants with Progressive Disease with spleen length more than 10 cm=increase of 50% from baseline in spleen length. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Missing Missing values. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 5 Years Adverse Events	2153 Participants	—	—	—
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 5 Years Serious adverse events	830 Participants	—	—	—

SECONDARY outcome

Timeframe: Baseline up to approximately 5 years

Population: Full analysis set includes all patients who received at least one administration of study drug.

Spleen length was assessed by manual palpation. Assessment of spleen response was repeated until early discontinuation of the study drug and also at study completion (28 days post end of treatment visit).

Outcome measures

Outcome measures
Measure	INC424 n=2049 Participants 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Stable Disease Participants with Stable Disease with spleen length between 5 and 10 cm=does not meet criteria for response or disease progression. Participants with Stable Disease with spleen length more than 10 cm=does not meet criteria for response or disease progression. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Progressive Disease Participants with Progressive Disease with spleen length between 5 and 10 cm=increase of 100% from baseline in spleen length. Participants with Progressive Disease with spleen length more than 10 cm=increase of 50% from baseline in spleen length. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Missing Missing values. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Percentage of Participants With at Least 50% Reduction in Spleen Length	71.7 percentage of participants Interval 69.7 to 73.7	—	—	—

SECONDARY outcome

Timeframe: Baseline up to approximately 5 years

Population: Full analysis set includes all patients who received at least one administration of study drug and were observed from baseline in to the study follow-up period.

Overall response is analyzed using the spleen response, as assessed by the investigator and also by deriving the response using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. Participants with spleen length at baseline between 5 and 10 cm were reported as Responders if reporting non palpable spleen; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 100% from baseline in spleen length. Participants with spleen length at baseline more than 10 cm were reported as Responders with spleen reduction of 50% from baseline; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 50% from baseline in spleen length.

Outcome measures

Outcome measures
Measure	INC424 n=2178 Participants 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Stable Disease n=2178 Participants Participants with Stable Disease with spleen length between 5 and 10 cm=does not meet criteria for response or disease progression. Participants with Stable Disease with spleen length more than 10 cm=does not meet criteria for response or disease progression. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Progressive Disease n=2178 Participants Participants with Progressive Disease with spleen length between 5 and 10 cm=increase of 100% from baseline in spleen length. Participants with Progressive Disease with spleen length more than 10 cm=increase of 50% from baseline in spleen length. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Missing n=2178 Participants Missing values. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length Spleen length at baseline-Less than 5 cm	NA Participants Patients with spleen length less than 5 cm are not evaluable (NE) for response.	NA Participants Patients with spleen length less than 5 cm are not evaluable (NE) for response.	NA Participants Patients with spleen length less than 5 cm are not evaluable (NE) for response.	NA Participants Patients with spleen length less than 5 cm are not evaluable (NE) for response.
Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length Spleen length at baseline-Between 5 and 10 cm	421 Participants	334 Participants	1 Participants	9 Participants
Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length Spleen length at baseline-More than 10 cm	742 Participants	463 Participants	0 Participants	19 Participants

SECONDARY outcome

Timeframe: Baseline up to approximately 5 years

Population: Full analysis set includes all patients who received at least one administration of study drug.

ECOG Performance Score has 5 grades. 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care. Totally confined to bed/chair. 5 = Death.

Outcome measures

Outcome measures
Measure	INC424 n=2233 Participants 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Stable Disease Participants with Stable Disease with spleen length between 5 and 10 cm=does not meet criteria for response or disease progression. Participants with Stable Disease with spleen length more than 10 cm=does not meet criteria for response or disease progression. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Progressive Disease Participants with Progressive Disease with spleen length between 5 and 10 cm=increase of 100% from baseline in spleen length. Participants with Progressive Disease with spleen length more than 10 cm=increase of 50% from baseline in spleen length. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Missing Missing values. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 0 · Worst value post-baseline: Grade 4	7 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 3 · Worst value post-baseline: Missing	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 4 · Worst value post-baseline: Grade 0	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 4 · Worst value post-baseline: Grade 1	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 0 · Worst value post-baseline: Grade 0	598 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 0 · Worst value post-baseline: Grade 1	377 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 0 · Worst value post-baseline: Grade 2	62 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 0 · Worst value post-baseline: Grade 3	12 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 0 · Worst value post-baseline: Grade 5	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 0 · Worst value post-baseline: Missing	5 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 1 · Worst value post-baseline: Grade 0	89 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 1 · Worst value post-baseline: Grade 1	629 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 1 · Worst value post-baseline: Grade 2	187 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 1 · Worst value post-baseline: Grade 3	26 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 1 · Worst value post-baseline: Grade 4	12 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 1 · Worst value post-baseline: Grade 5	1 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 1 · Worst value post-baseline: Missing	16 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 2 · Worst value post-baseline: Grade 0	3 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 2 · Worst value post-baseline: Grade 1	43 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 2 · Worst value post-baseline: Grade 2	111 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 2 · Worst value post-baseline: Grade 3	20 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 2 · Worst value post-baseline: Grade 4	12 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 2 · Worst value post-baseline: Grade 5	1 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 2 · Worst value post-baseline: Missing	7 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 3 · Worst value post-baseline: Grade 0	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 3 · Worst value post-baseline: Grade 1	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 3 · Worst value post-baseline: Grade 2	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 3 · Worst value post-baseline: Grade 3	1 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 3 · Worst value post-baseline: Grade 4	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 3 · Worst value post-baseline: Grade 5	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 4 · Worst value post-baseline: Grade 2	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 4 · Worst value post-baseline: Grade 3	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 4 · Worst value post-baseline: Grade 4	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 4 · Worst value post-baseline: Grade 5	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Grade 4 · Worst value post-baseline: Missing	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Missing · Worst value post-baseline: Grade 0	1 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Missing · Worst value post-baseline: Grade 1	8 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Missing · Worst value post-baseline: Grade 2	4 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Missing · Worst value post-baseline: Grade 3	1 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Missing · Worst value post-baseline: Grade 4	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Missing · Worst value post-baseline: Grade 5	0 Participants	—	—	—
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years Baseline - Missing · Worst value post-baseline: Missing	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: Full analysis set includes all patients who received at least one administration of study drug.

The FACT-Lym questionnaire consists of a total of 42 questions divided between five subscales (i.e., physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma subscale). Each subscale questionnaire rates each question on a 5-point scale from 0 = Not at all to 4 = Very much. These scores were summed to three total sum scores, namely FACT-Lym score, FACT-Lym Trial Outcome Index (TOI), FACT-General (FACT-G) and FACT-Lym total score. Total scores: FACT-Lym=0-60, FACT-TOI=0-116, FACT-G total=0-108, FACT-Lym Total= 0-168. Higher scores are reflective of better HRQoL.

Outcome measures

Outcome measures
Measure	INC424 n=2233 Participants 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Stable Disease Participants with Stable Disease with spleen length between 5 and 10 cm=does not meet criteria for response or disease progression. Participants with Stable Disease with spleen length more than 10 cm=does not meet criteria for response or disease progression. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Progressive Disease Participants with Progressive Disease with spleen length between 5 and 10 cm=increase of 100% from baseline in spleen length. Participants with Progressive Disease with spleen length more than 10 cm=increase of 50% from baseline in spleen length. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Missing Missing values. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 FACT-Lymphoma Baseline	42.3 scores on a scale Standard Deviation 10.20	—	—	—
Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 FACT-Lymphoma Week 48	47.9 scores on a scale Standard Deviation 8.47	—	—	—
Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 FACT-Lymphoma TOI Baseline	77.9 scores on a scale Standard Deviation 18.99	—	—	—
Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 FACT-Lymphoma TOI Week 48	86.8 scores on a scale Standard Deviation 16.42	—	—	—
Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 FACT-Lymphoma total score Baseline	113.9 scores on a scale Standard Deviation 24.01	—	—	—
Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 FACT-Lymphoma total score Week 48	123.3 scores on a scale Standard Deviation 22.34	—	—	—
Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 FACT-G Baseline	71.6 scores on a scale Standard Deviation 15.98	—	—	—
Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 FACT-G Week 48	75.5 scores on a scale Standard Deviation 15.59	—	—	—

SECONDARY outcome

Timeframe: Baseline up to approximately 5 years

Population: Full analysis set includes all patients who received at least one administration of study drug.

Improvement was defined by the upper limit of the minimally important difference (MID). Patients with the best possible score at Baseline were excluded from this analysis because their HRQoL cannot be further improved. Responders and non-responders for each endpoint were defined based on change from baseline scores using pre specified cut-off points. Patients with an improved score compared to Baseline, for which the magnitude of the change was at least the cutoff value, were classified as responders; otherwise, as non-responders. The responder cutoff: ECOG cutoff=1, range=0 to 5, FACT-Lym cutoff=5.4, range 0-60, FACIT-Fatigue =5 and range=0-52.The median time to first improvement was estimated using the Kaplan Meier method and time to improvement event was determined based on upper bound of the MID. The time to improvement was calculated from the date of first study drug administration.

Outcome measures

Outcome measures
Measure	INC424 n=2233 Participants 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Stable Disease Participants with Stable Disease with spleen length between 5 and 10 cm=does not meet criteria for response or disease progression. Participants with Stable Disease with spleen length more than 10 cm=does not meet criteria for response or disease progression. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Progressive Disease Participants with Progressive Disease with spleen length between 5 and 10 cm=increase of 100% from baseline in spleen length. Participants with Progressive Disease with spleen length more than 10 cm=increase of 50% from baseline in spleen length. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Missing Missing values. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status FACT-Lym Total score median time to improvement	10.9 weeks Interval 5.1 to 11.6	—	—	—
Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status FACIT - Fatigue score median time to improvement	4.6 weeks Interval 4.4 to 4.6	—	—	—
Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status ECOG score median time to improvement	63.1 weeks Interval 61.1 to 65.0	—	—	—

SECONDARY outcome

Timeframe: Baseline up to approximately 5 years.

Population: Full analysis set includes all patients who received at least one administration of study drug.

Percentage of patients requiring medical resources (blood transfusions, hospitalization, emergency room visits, general practitioners or specialists consultations, urgent care or splenic irradiation) up to 5 years.

Outcome measures

Outcome measures
Measure	INC424 n=2233 Participants 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Stable Disease Participants with Stable Disease with spleen length between 5 and 10 cm=does not meet criteria for response or disease progression. Participants with Stable Disease with spleen length more than 10 cm=does not meet criteria for response or disease progression. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Progressive Disease Participants with Progressive Disease with spleen length between 5 and 10 cm=increase of 100% from baseline in spleen length. Participants with Progressive Disease with spleen length more than 10 cm=increase of 50% from baseline in spleen length. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	INC424 - Missing Missing values. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Medical Resource Utilization up to 5 Years Baseline- Dependency · End of Study - Dependency	129 Participants	—	—	—
Medical Resource Utilization up to 5 Years Baseline- Dependency · End of Study - Independency	29 Participants	—	—	—
Medical Resource Utilization up to 5 Years Baseline- Independency · End of Study - Dependency	480 Participants	—	—	—
Medical Resource Utilization up to 5 Years Baseline- Independency · End of Study - Independency	1595 Participants	—	—	—

Adverse Events

INC424

Serious events: 830 serious events

Other events: 2008 other events

Deaths: 205 deaths

Serious adverse events

Serious adverse events
Measure	INC424 n=2233 participants at risk All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 25 mg twice a day. No INC424 dose will exceed 20 mg BID orally.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Skin and subcutaneous tissue disorders Skin mass	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Skin and subcutaneous tissue disorders Skin ulcer	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Surgical and medical procedures Stem cell transplant	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Aortic aneurysm	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Aortic rupture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Aortic stenosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Arterial disorder	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Arterial haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.2% 26/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Thoracic haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Skin and subcutaneous tissue disorders Dermal cyst	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Skin and subcutaneous tissue disorders Dermatitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Skin and subcutaneous tissue disorders Erythema nodosum	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Skin and subcutaneous tissue disorders Panniculitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Skin and subcutaneous tissue disorders Pruritus	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Agranulocytosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Anaemia	4.2% 94/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Autoimmune haemolytic anaemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Bone marrow oedema	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Coagulopathy	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Febrile neutropenia	0.36% 8/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Haemolytic anaemia	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Histiocytosis haematophagic	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Hypercoagulation	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Leukocytosis	0.36% 8/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Leukostasis syndrome	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Lymphadenopathy	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Lymphocytosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Monoclonal B-cell lymphocytosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Neutropenia	0.45% 10/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Pancytopenia	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Polycythaemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Splenic haematoma	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Splenic infarction	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Splenomegaly	0.36% 8/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Spontaneous haematoma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Thrombocytopenia	1.1% 24/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Thrombocytosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Acute coronary syndrome	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Acute myocardial infarction	0.40% 9/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Angina pectoris	0.36% 8/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Aortic valve incompetence	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Atrial fibrillation	0.94% 21/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Atrioventricular block	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Atrioventricular block first degree	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Bradycardia	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Cardiac arrest	0.72% 16/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Cardiac disorder	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Cardiac failure	1.9% 43/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Cardiac failure acute	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Cardiac failure chronic	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Cardiac failure congestive	0.31% 7/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Cardiac tamponade	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Cardio-respiratory arrest	0.40% 9/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Cardiogenic shock	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Cardiopulmonary failure	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Conduction disorder	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Congestive cardiomyopathy	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Cor pulmonale	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Coronary artery disease	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Coronary artery stenosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Hypertensive heart disease	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Intracardiac thrombus	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Left ventricular dysfunction	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Left ventricular failure	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Left ventricular hypertrophy	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Mitral valve incompetence	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Myocardial infarction	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Myocardial ischaemia	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Palpitations	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Pericardial effusion	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Pericardial haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Pericarditis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Right ventricular dysfunction	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Right ventricular failure	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Sinus node dysfunction	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Sinus tachycardia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Stress cardiomyopathy	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Supraventricular tachycardia	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Tachyarrhythmia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Tachycardia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Tricuspid valve incompetence	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Ventricular dysfunction	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Cardiac disorders Ventricular hypokinesia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Congenital, familial and genetic disorders Hydrocele	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Ear and labyrinth disorders Hypoacusis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Ear and labyrinth disorders Vertigo	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Endocrine disorders Adrenal insufficiency	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Eye disorders Cataract	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Eye disorders Corneal oedema	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Eye disorders Diplopia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Eye disorders Macular degeneration	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Eye disorders Optic ischaemic neuropathy	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Eye disorders Uveitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Abdominal hernia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Abdominal mass	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Abdominal pain	1.3% 28/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Abdominal pain lower	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Abdominal pain upper	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Abdominal tenderness	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Abdominal wall haematoma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Anal fissure	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Anal prolapse	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Anal ulcer	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Ascites	0.63% 14/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Barrett's oesophagus	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Colitis	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Constipation	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Diarrhoea	0.76% 17/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Diarrhoea haemorrhagic	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Diverticular perforation	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Enteritis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Enterovesical fistula	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Faecaloma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Femoral hernia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Gastric haemorrhage	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Gastric stenosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Gastric ulcer	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Gastric varices haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Gastritis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.94% 21/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Haematemesis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Haematochezia	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Haemorrhoids	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Ileus	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Ileus paralytic	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Inguinal hernia	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Inguinal hernia strangulated	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Intestinal haemorrhage	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Intestinal infarction	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Intestinal obstruction	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Intestinal perforation	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Mallory-Weiss syndrome	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Melaena	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Mesenteric haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Mesenteric vein thrombosis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Mouth haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Nausea	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Oesophageal haemorrhage	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Oesophageal rupture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.45% 10/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Pancreatitis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Peritoneal haemorrhage	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Pneumoperitoneum	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Rectal haemorrhage	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Rectal polyp	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Retroperitoneal haematoma	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Retroperitoneal haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Small intestinal obstruction	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Small intestinal stenosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Splenic artery aneurysm	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Subileus	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Tooth loss	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Toothache	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Varices oesophageal	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Vomiting	0.72% 16/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Asthenia	0.63% 14/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Chest pain	0.36% 8/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Death	0.54% 12/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Disease progression	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Drug withdrawal syndrome	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Face oedema	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Fatigue	0.49% 11/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Gait disturbance	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders General physical health deterioration	0.85% 19/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Generalised oedema	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Hernia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Hyperpyrexia	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Malaise	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Multiple organ dysfunction syndrome	0.49% 11/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Nodule	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Non-cardiac chest pain	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Oedema peripheral	0.45% 10/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Pain	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Peripheral swelling	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Polyp	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Pseudocyst	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Pyrexia	3.5% 79/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Sudden death	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Bile duct stone	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Biliary colic	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Cholangitis chronic	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Cholecystitis	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Cholecystitis acute	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Cholelithiasis	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Hepatic failure	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Hepatitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Hepatorenal syndrome	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Hepatotoxicity	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Hyperbilirubinaemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Jaundice	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Portal hypertension	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Hepatobiliary disorders Portal vein thrombosis	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Immune system disorders Cytokine release syndrome	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Immune system disorders Hypersensitivity	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Immune system disorders Immunosuppression	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Actinomycosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Anal abscess	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Appendicitis	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Arthritis bacterial	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Aspergillus infection	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Atypical pneumonia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Bacterial infection	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Biliary sepsis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Bone tuberculosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Bronchitis	0.40% 9/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Bronchitis bacterial	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Bronchopulmonary aspergillosis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Campylobacter infection	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Cellulitis	0.36% 8/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Cerebral toxoplasmosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Community acquired infection	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Corneal abscess	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Cystitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Dengue fever	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Dermo-hypodermitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Device related infection	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Device related sepsis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Diverticulitis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Endocarditis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Enterococcal infection	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Enterococcal sepsis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Epididymitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Erysipelas	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Escherichia infection	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Escherichia sepsis	0.27% 6/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Escherichia urinary tract infection	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Gangrene	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Gastroenteritis	0.49% 11/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Gastroenteritis norovirus	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Gastroenteritis salmonella	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Gastroenteritis viral	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Gastrointestinal infection	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Genital herpes	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations H1N1 influenza	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Hepatic echinococciasis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Hepatitis B	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Hepatitis E	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Hepatitis infectious	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Herpes simplex	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Herpes simplex pneumonia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Herpes zoster	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Skin and subcutaneous tissue disorders Skin lesion	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Herpes zoster infection neurological	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Infection	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Infectious pleural effusion	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Influenza	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Klebsiella infection	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Localised infection	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Lower respiratory tract infection	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Lung abscess	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Lung infection	0.49% 11/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Lymph node tuberculosis	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Meningitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Mycobacterial infection	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Neurocryptococcosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Ophthalmic herpes zoster	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Oral candidiasis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Pelvic inflammatory disease	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Perirectal abscess	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Peritoneal tuberculosis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Peritonitis	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Peritonitis bacterial	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Pharyngitis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Pneumococcal infection	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Pneumocystis jirovecii infection	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Pneumonia	5.5% 123/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Pneumonia bacterial	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Pneumonia pneumococcal	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Pseudomonal sepsis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Psoas abscess	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Pulmonary sepsis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Pulmonary tuberculosis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Pulpitis dental	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Pyelonephritis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Q fever	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Respiratory syncytial virus infection	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Respiratory tract infection	0.85% 19/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Sepsis	1.4% 31/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Septic shock	0.94% 21/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Sinusitis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Skin infection	0.27% 6/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Soft tissue infection	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Staphylococcal infection	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Staphylococcal sepsis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Streptococcal sepsis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Subcutaneous abscess	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Tooth abscess	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Tracheitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Tracheobronchitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Tuberculosis	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Tubo-ovarian abscess	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Upper respiratory tract infection	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Urinary tract infection	1.0% 23/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Urinary tract infection bacterial	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Urosepsis	0.36% 8/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Vestibular neuronitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Viral infection	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Anastomotic leak	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Ankle fracture	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Arterial injury	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Brain contusion	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Craniocerebral injury	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Crush injury	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Face injury	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Facial bones fracture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Fall	0.27% 6/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Femoral neck fracture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Femur fracture	0.27% 6/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Foot fracture	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Fractured sacrum	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Head injury	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Heart injury	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Hip fracture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Humerus fracture	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Joint injury	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Limb injury	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Lower limb fracture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Meniscus injury	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Overdose	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Patella fracture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Rib fracture	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Road traffic accident	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Spinal compression fracture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Spinal fracture	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Splenic injury	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Splenic rupture	0.31% 7/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Subarachnoid haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Subdural haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Tendon rupture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Transfusion reaction	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Traumatic fracture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Traumatic haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Upper limb fracture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Injury, poisoning and procedural complications Wound dehiscence	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Blast cell count increased	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Blood alkaline phosphatase increased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Blood lactate dehydrogenase increased	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Body temperature increased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations C-reactive protein increased	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Cardioactive drug level increased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Ejection fraction decreased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Electrocardiogram QT prolonged	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Electrocardiogram T wave abnormal	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Electrocardiogram T wave amplitude increased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Epstein-Barr virus antigen positive	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Gamma-glutamyltransferase increased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations General physical condition abnormal	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Haemoglobin decreased	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Heart rate irregular	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Hepatic enzyme increased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Lipase increased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Myeloblast count increased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Platelet count decreased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Portal vein pressure increased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Sensory level abnormal	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Transaminases increased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Troponin I increased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations White blood cell count increased	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Cachexia	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Decreased appetite	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Dehydration	0.36% 8/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Diabetes mellitus	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Diabetic metabolic decompensation	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Electrolyte imbalance	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Fluid retention	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Gout	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Hypercalcaemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Hyperkalaemia	0.36% 8/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Hyperlactacidaemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Hyperuricaemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Hypocalcaemia	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Hypoglycaemia	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Hypokalaemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Hyponatraemia	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Hypophosphataemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Hypovolaemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Metabolic acidosis	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Metabolism and nutrition disorders Tumour lysis syndrome	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Arthralgia	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Arthritis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Arthropathy	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Back pain	0.36% 8/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Bone pain	0.49% 11/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Chondrocalcinosis pyrophosphate	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Compartment syndrome	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Crystal arthropathy	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Flank pain	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Meniscal degeneration	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Muscle tightness	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Muscular weakness	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Myalgia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Neck pain	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Osteolysis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Osteoporotic fracture	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Pain in extremity	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Soft tissue necrosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acrochordon	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute leukaemia	0.58% 13/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.81% 18/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.45% 10/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Blast cell crisis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chloroma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia transformation	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myelomonocytic leukaemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intestinal adenocarcinoma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	0.31% 7/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphangioma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Monoclonal gammopathy	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelofibrosis	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myeloid metaplasia	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm skin	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pelvic neoplasm	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Second primary malignancy	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.40% 9/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.27% 6/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the vagina	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour thrombosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Basilar artery aneurysm	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Central nervous system haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Central nervous system lesion	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Cerebral haemorrhage	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Cerebral ischaemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Cerebrovascular accident	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Coma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Cranial nerve paralysis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Dizziness	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Drop attacks	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Dysarthria	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Embolic stroke	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Encephalopathy	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Extrapyramidal disorder	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Generalised tonic-clonic seizure	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Haemorrhagic stroke	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Headache	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Hepatic encephalopathy	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Hydrocephalus	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Hyperaesthesia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Ischaemic stroke	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Loss of consciousness	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Muscle contractions involuntary	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Myoclonus	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Neuralgia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Neurological decompensation	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Neuropathy peripheral	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Osmotic demyelination syndrome	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Paraesthesia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Parkinson's disease	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Posterior reversible encephalopathy syndrome	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Presyncope	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Pyramidal tract syndrome	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Sciatica	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Seizure	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Somnolence	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Speech disorder	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Syncope	0.49% 11/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Transient ischaemic attack	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Product Issues Device leakage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Psychiatric disorders Anxiety	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Psychiatric disorders Anxiety disorder	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Psychiatric disorders Confusional state	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Psychiatric disorders Delirium	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Psychiatric disorders Depression	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Psychiatric disorders Disorientation	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Acute kidney injury	0.85% 19/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Acute prerenal failure	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Anuria	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Calculus bladder	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Chronic kidney disease	0.27% 6/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Dysuria	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Haematuria	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Hydronephrosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Nephrolithiasis	0.27% 6/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Nephropathy	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Nephrotic syndrome	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Renal colic	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Renal failure	0.54% 12/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Renal impairment	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Renal infarct	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Renal and urinary disorders Tubulointerstitial nephritis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Reproductive system and breast disorders Cervical dysplasia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Reproductive system and breast disorders Menometrorrhagia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Reproductive system and breast disorders Ovarian cyst	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Reproductive system and breast disorders Postmenopausal haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Reproductive system and breast disorders Prostatitis	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Reproductive system and breast disorders Testicular pain	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.31% 7/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.31% 7/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Alveolitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Asthma	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Chronic respiratory failure	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Cough	0.27% 6/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.6% 36/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Emphysema	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.45% 10/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.18% 4/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.58% 13/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.22% 5/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Productive cough	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.81% 18/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.36% 8/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Circulatory collapse	0.09% 2/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Deep vein thrombosis	0.45% 10/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Embolism	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Haematoma	0.40% 9/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Hyperaemia	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Hypertension	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Hypertensive crisis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Hypotension	0.31% 7/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Pallor	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Peripheral artery occlusion	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Peripheral artery stenosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Peripheral ischaemia	0.13% 3/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Phlebitis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Shock	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Thrombophlebitis superficial	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Vascular disorders Venous thrombosis	0.04% 1/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.

Other adverse events

Other adverse events
Measure	INC424 n=2233 participants at risk All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 25 mg twice a day. No INC424 dose will exceed 20 mg BID orally.
Blood and lymphatic system disorders Anaemia	58.2% 1300/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Neutropenia	6.5% 146/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Blood and lymphatic system disorders Thrombocytopenia	44.3% 990/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Abdominal pain	6.7% 149/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Constipation	5.4% 121/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Diarrhoea	12.0% 267/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Gastrointestinal disorders Nausea	5.7% 128/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Asthenia	14.8% 331/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Fatigue	9.6% 215/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Oedema peripheral	8.2% 182/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
General disorders Pyrexia	13.9% 310/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Herpes zoster	5.0% 112/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Nasopharyngitis	5.2% 115/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Infections and infestations Urinary tract infection	5.1% 114/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Alanine aminotransferase increased	6.0% 134/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Platelet count decreased	8.9% 198/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Investigations Weight increased	6.3% 140/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Arthralgia	7.9% 176/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Back pain	5.2% 115/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Musculoskeletal and connective tissue disorders Pain in extremity	6.6% 147/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Nervous system disorders Headache	8.6% 191/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 186/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.9% 155/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Skin and subcutaneous tissue disorders Pruritus	5.9% 131/2233 • Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years . Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
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