Trial Outcomes & Findings for A Phase 2 Trial of Ponatinib in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor (NCT NCT01874665)

NCT ID: NCT01874665

Last Updated: 2018-05-18

Results Overview

To assess clinical benefit rate in participants with KIT exon 11-mutant GIST.It is defined as the composite of complete response(CR),partial response(PR),and stable disease(SD) lasting \>=16 weeks per modified Response Evaluation Criteria In Solid Tumors(RECIST) 1.1 as a measure of disease control.CR is complete disappearance of all target lesions and non-target disease, with the exception of nodal disease.All nodes, both target and non-target, must decrease to normal (short axis \<10millimeter \[mm\]).No new lesions.PR is \>=30% decrease under baseline of the sum of diameters of all target lesions.The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions.No unequivocal progression of non-target disease.No new lesions.SD is not qualifying for CR,PR,Progressive Disease(PD).PD is \>=20% increase from the smallest prior sum of the longest diameter(SLD)and with \>=5mm absolute increase, or appearance of a new lesion.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 45 participants
• Primary outcome timeframe: 16 weeks after first dose
• Results posted on: 2018-05-18

Participant Flow

Participant milestones

Measure	Cohort A Participants with KIT exon 11-mutant GIST ponatinib: 45 milligram (mg), taken orally once-daily.	Cohort B Participants with gastrointestinal stromal tumors (GIST) that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Overall Study STARTED	30	15
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	30	15

Reasons for withdrawal

Measure	Cohort A Participants with KIT exon 11-mutant GIST ponatinib: 45 milligram (mg), taken orally once-daily.	Cohort B Participants with gastrointestinal stromal tumors (GIST) that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Overall Study Adverse Event	6	2
Overall Study Withdrawal by Subject	4	1
Overall Study Physician Decision	3	0
Overall Study Clinical Progressive Disease	4	3
Overall Study Study Terminated by Sponsor	0	2
Overall Study Documented Progressive Disease	11	7
Overall Study Other	2	0

Baseline Characteristics

The ITT population included all participants who received any dose of ponatinib in the study.

Baseline characteristics by cohort

Measure	Cohort A n=30 Participants Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B n=15 Participants Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.	Total n=45 Participants Total of all reporting groups
Age, Continuous	59.3 years STANDARD_DEVIATION 10.37 • n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	53.9 years STANDARD_DEVIATION 16.06 • n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	57.5 years STANDARD_DEVIATION 12.63 • n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Sex: Female, Male Female	11 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	8 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	19 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Sex: Female, Male Male	19 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	7 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	26 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	1 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	15 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	44 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Race (NIH/OMB) Asian	0 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Race (NIH/OMB) White	29 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	15 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	44 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	0 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	1 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Region of Enrollment United States	30 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	15 Participants n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	45 Participants n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Weight	80.12 kilogram (kg) STANDARD_DEVIATION 20.699 • n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	75.10 kilogram (kg) STANDARD_DEVIATION 13.917 • n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	78.45 kilogram (kg) STANDARD_DEVIATION 18.702 • n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.
Height	171.20 centimeter (cm) STANDARD_DEVIATION 7.839 • n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	171.28 centimeter (cm) STANDARD_DEVIATION 7.149 • n=7 Participants • The ITT population included all participants who received any dose of ponatinib in the study.	171.23 centimeter (cm) STANDARD_DEVIATION 7.534 • n=5 Participants • The ITT population included all participants who received any dose of ponatinib in the study.

PRIMARY outcome

Timeframe: 16 weeks after first dose

Population: The ITT population included all participants who received any dose of ponatinib in the study. The ITT population where data at specified time points was available.

To assess clinical benefit rate in participants with KIT exon 11-mutant GIST.It is defined as the composite of complete response(CR),partial response(PR),and stable disease(SD) lasting >=16 weeks per modified Response Evaluation Criteria In Solid Tumors(RECIST) 1.1 as a measure of disease control.CR is complete disappearance of all target lesions and non-target disease, with the exception of nodal disease.All nodes, both target and non-target, must decrease to normal (short axis <10millimeter [mm]).No new lesions.PR is >=30% decrease under baseline of the sum of diameters of all target lesions.The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions.No unequivocal progression of non-target disease.No new lesions.SD is not qualifying for CR,PR,Progressive Disease(PD).PD is >=20% increase from the smallest prior sum of the longest diameter(SLD)and with >=5mm absolute increase, or appearance of a new lesion.

Outcome measures

Measure	Cohort A n=28 Participants Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Clinical Benefit Rate (CBR) in Cohort A	35.7 percentage (%) of participants Interval 18.6 to 55.9	—

SECONDARY outcome

Timeframe: 16 weeks after first dose

Population: The ITT population included all participants who received any dose of ponatinib in the study.

To assess clinical benefit rate in participants with GIST that lacks KIT exon 11 mutations (Cohort B) and in the total participant population. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 millimeter [mm]). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. SD was defined as not qualifying for CR, PR, PD.

Outcome measures

Measure	Cohort A n=15 Participants Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Clinical Benefit Rate (CBR) in Cohort B	20.0 percentage (%) of participants Interval 4.3 to 48.1	—

SECONDARY outcome

Timeframe: From date of enrollment until the end of the study or disease progression or death due to any cause, whichever came first, assessed up to 3 years

Population: The ITT population included all participants who received any dose of ponatinib in the study.

PFS is defined as the duration of time from start of study drug administration to time of objective disease progression or death due to any cause, whichever may come first. To assess PFS in each cohort and in the total participant population.

Outcome measures

Measure	Cohort A n=30 Participants Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B n=15 Participants Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Progression-free Survival (PFS)	112.0 days Interval 57.0 to 252.0	57.0 days Interval 55.0 to 502.0

SECONDARY outcome

Timeframe: From date of enrollment until discontinuation or the end of the study, whichever came first, assessed up to 3 years

Population: The ITT population included all participants who received any dose of ponatinib in the study. The ITT population where data at specified time points was available.

ORR is defined as the composite of CR and PR per Response Evaluation Criteria in RECIST 1.1, assessed for each cohort and in the total participant population. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions.

Outcome measures

Measure	Cohort A n=28 Participants Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B n=15 Participants Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Percentage of Participants With Objective Response Rate (ORR)	7.1 percentage of participants Interval 0.9 to 23.5	0.0 percentage of participants Interval 0.0 to 21.8

SECONDARY outcome

Timeframe: From first dose of drug until the end of the study or death, whichever came first, assessed up to 3 years

Population: The ITT population included all participants who received any dose of ponatinib in the study.

OS is defined as the time interval between the first dose of study drug to death due to any cause. Overall survival was analyzed using the Kaplan-Meier method.

Outcome measures

Measure	Cohort A n=30 Participants Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B n=15 Participants Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Overall Survival (OS)	411.0 days Interval 234.0 to 836.0	399.0 days Interval 90.0 to Upper limit of confidence interval was not estimable.

SECONDARY outcome

Timeframe: From date of enrollment until the End-of-Treatment, assessed up to 3 years

Population: The ITT population included all participants who received any dose of ponatinib in the study.

Outcome measures

Measure	Cohort A n=30 Participants Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B n=15 Participants Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Number of Participants With Physical Examination	6 Participants	1 Participants

SECONDARY outcome

Timeframe: From date of enrollment until the End-of-Treatment, assessed up to 3 years

Population: The ITT population included all participants who received any dose of ponatinib in the study.

Outcome measures

Measure	Cohort A n=30 Participants Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B n=15 Participants Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Sign Measurements Hypertension	15 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Sign Measurements Procedural hypotension	1 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Sign Measurements Pyrexia	7 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Sign Measurements Chills	3 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Sign Measurements Feeling of body temperature change	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From date of enrollment until the End-of-Treatment, assessed up to 3 years

Population: The ITT population included all participants who received any dose of ponatinib in the study.

Outcome measures

Measure	Cohort A n=30 Participants Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B n=15 Participants Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Albumin decreased	13 Participants	4 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Alkaline phosphatase increased	12 Participants	8 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Alanine aminotransferase (ALT) increased	11 Participants	7 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Amylase	3 Participants	5 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Absolute neutrophil count (ANC) decreased	2 Participants	0 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Aspartate aminotransferase (AST) increased	11 Participants	8 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Bicarbonate decreased	1 Participants	1 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Bilirubin	4 Participants	2 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Calcium decreased	5 Participants	4 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Calcium increased	5 Participants	1 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Creatinine increased	3 Participants	3 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Glucose decreased	1 Participants	3 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Glucose increased	19 Participants	9 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Hemoglobin decreased	10 Participants	5 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Lipase increased	6 Participants	7 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Lymphocytes (ALC)/ lymphopenia	5 Participants	4 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Phosphorus decreased	5 Participants	1 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Platelets decreased	2 Participants	0 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Potassium decreased	5 Participants	2 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Potassium increased	8 Participants	3 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Sodium decreased	8 Participants	1 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Sodium increased	7 Participants	2 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters Triglycerides increased	2 Participants	0 Participants
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters White blood cells (WBC) decreased	2 Participants	0 Participants

SECONDARY outcome

Timeframe: From date of enrollment until the End-of-Treatment, assessed up to 3 years

Population: The ITT population included all participants who received any dose of ponatinib in the study.

Outcome measures

Measure	Cohort A n=30 Participants Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B n=15 Participants Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Findings Ejection Fraction Decreased	1 Participants	2 Participants
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Findings Atrial Fibrillation	1 Participants	2 Participants
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Findings Sinus Tachycardia	1 Participants	1 Participants
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Findings Cardiac Failure Congestive	1 Participants	0 Participants
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Findings Myocardial Ischaemia	1 Participants	0 Participants
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Findings Pericardial Effusion	0 Participants	1 Participants
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Findings Right Ventricular Dysfunction	1 Participants	0 Participants
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Findings Sinus Bradycardia	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From date of enrollment until the End-of-Treatment, assessed up to 3 years

Population: The ITT population included all participants who received any dose of ponatinib in the study.

Outcome measures

Measure	Cohort A n=30 Participants Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B n=15 Participants Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Number of Participants With TEAEs Related to Echocardiography Parameter Congestive Cardiac Failure	1 Participants	0 Participants
Number of Participants With TEAEs Related to Echocardiography Parameter Right Ventricular Dysfunction	1 Participants	0 Participants
Number of Participants With TEAEs Related to Echocardiography Parameter Decreased Ejection Fraction	1 Participants	2 Participants
Number of Participants With TEAEs Related to Echocardiography Parameter Pulmonary Oedema	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From date of enrollment until the End-of-Treatment, assessed up to 3 years

Population: The ITT population included all participants who received any dose of ponatinib in the study.

Outcome measures

Measure	Cohort A n=30 Participants Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B n=15 Participants Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Number of Participants Reporting One or More TEAEs and Serious Adverse Event (SAE) TEAE	30 Participants	15 Participants
Number of Participants Reporting One or More TEAEs and Serious Adverse Event (SAE) SAE	20 Participants	6 Participants

SECONDARY outcome

Timeframe: Pre-dose and at multiple timepoints (up to 1 month) post-dose

Population: Data was not collected for Cmax,ss, since outcome measure was not planned to be analyzed.

Outcome measures

Outcome data not reported

Adverse Events

Cohort A

Serious events: 20 serious events

Other events: 30 other events

Deaths: 4 deaths

Cohort B

Serious events: 6 serious events

Other events: 15 other events

Deaths: 2 deaths

Serious adverse events

Measure	Cohort A n=30 participants at risk Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B n=15 participants at risk Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Blood and lymphatic system disorders ANAEMIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders ATRIAL FIBRILLATION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders MYOCARDIAL ISCHAEMIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders RIGHT VENTRICULAR DYSFUNCTION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders ABDOMINAL PAIN	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders DUODENAL STENOSIS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders NAUSEA	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders OBSTRUCTION GASTRIC	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders SMALL INTESTINAL OBSTRUCTION	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders SMALL INTESTINAL ULCER PERFORATION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders UPPER GASTROINTESTINAL HAEMORRHAGE	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders VOMITING	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders FATIGUE	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders HEPATIC FAILURE	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations COLONIC ABSCESS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations PNEUMONIA	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations SEPSIS	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations URINARY TRACT INFECTION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications HIP FRACTURE	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders DEHYDRATION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders HYPERCALCAEMIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) NEOPLASM PROGRESSION	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOUR HAEMORRHAGE	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders CEREBROVASCULAR ACCIDENT	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders SYNCOPE	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders ACUTE RESPIRATORY FAILURE	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders HYPOXIA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders DEEP VEIN THROMBOSIS	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders PERIPHERAL ARTERY STENOSIS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders CARDIAC FAILURE CONGESTIVE	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders SPINAL CORD COMPRESSION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Measure	Cohort A n=30 participants at risk Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.	Cohort B n=15 participants at risk Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.
Blood and lymphatic system disorders ANAEMIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 5/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders ATRIAL FIBRILLATION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Endocrine disorders HYPOTHYROIDISM	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders ABDOMINAL PAIN	46.7% 14/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	40.0% 6/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders ASCITES	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders CONSTIPATION	46.7% 14/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 5/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders DIARRHOEA	26.7% 8/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders DRY MOUTH	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders DYSPEPSIA	13.3% 4/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	26.7% 4/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders NAUSEA	20.0% 6/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 3/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders STOMATITIS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders VOMITING	23.3% 7/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders CHILLS	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders FATIGUE	50.0% 15/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	60.0% 9/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders NON-CARDIAC CHEST PAIN	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders OEDEMA PERIPHERAL	43.3% 13/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 3/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders PAIN	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders PYREXIA	23.3% 7/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 3/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations PNEUMONIA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations URINARY TRACT INFECTION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 3/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications FALL	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations ALANINE AMINOTRANSFERASE INCREASED	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 5/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations AMYLASE INCREASED	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	16.7% 5/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 5/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations BLOOD ALKALINE PHOSPHATASE INCREASED	23.3% 7/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	40.0% 6/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations EJECTION FRACTION DECREASED	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations LIPASE INCREASED	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	26.7% 4/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations WEIGHT DECREASED	20.0% 6/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders DECREASED APPETITE	36.7% 11/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	26.7% 4/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders DEHYDRATION	16.7% 5/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders HYPERGLYCAEMIA	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 3/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders HYPOPHOSPHATAEMIA	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders ARTHRALGIA	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	26.7% 4/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders BACK PAIN	23.3% 7/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders BONE PAIN	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	16.7% 5/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders MYALGIA	50.0% 15/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 3/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders NECK PAIN	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	13.3% 4/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOUR HAEMORRHAGE	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders DIZZINESS	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders HEADACHE	43.3% 13/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	46.7% 7/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders PERIPHERAL SENSORY NEUROPATHY	13.3% 4/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders INSOMNIA	13.3% 4/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders URINARY RETENTION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Reproductive system and breast disorders ERECTILE DYSFUNCTION	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders COUGH	26.7% 8/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	26.7% 4/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders DYSPHONIA	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	26.7% 4/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	13.3% 4/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	10.0% 3/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders ALOPECIA	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders DRY SKIN	36.7% 11/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	26.7% 4/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders HYPERHIDROSIS	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 3/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders PRURITUS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.0% 3/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders RASH	50.0% 15/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	80.0% 12/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders HYPERTENSION	50.0% 15/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders LEUKOCYTOSIS	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders IRON DEFICIENCY ANAEMIA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders LYMPH NODE PAIN	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders SINUS TACHYCARDIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders PERICARDIAL EFFUSION	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders SINUS BRADYCARDIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders ABDOMINAL DISCOMFORT	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders ABDOMINAL DISTENSION	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders ABDOMINAL TENDERNESS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders COLITIS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders DYSPHAGIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders ERUCTATION	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders GASTRIC ULCER	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders HAEMORRHOIDS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders OBSTRUCTION GASTRIC	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders OESOPHAGEAL PAIN	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders PROCTALGIA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders TOOTHACHE	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders UPPER GASTROINTESTINAL HAEMORRHAGE	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations CELLULITIS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations CLOSTRIDIUM DIFFICILE INFECTION	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations CYSTITIS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations DIVERTICULITIS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations INFECTION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations ORAL CANDIDIASIS	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations ORAL INFECTION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations OTITIS MEDIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations POSTOPERATIVE WOUND INFECTION	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations PYURIA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations SKIN INFECTION	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations TOOTH INFECTION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications HEAD INJURY	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications HIP FRACTURE	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications INCISION SITE HAEMATOMA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications LOWER LIMB FRACTURE	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications POST PROCEDURAL HAEMORRHAGE	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications PROCEDURAL HYPOTENSION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications PROCEDURAL PAIN	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations PLATELET COUNT DECREASED	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations BLOOD BILIRUBIN INCREASED	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations BLOOD CREATININE INCREASED	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders FLANK PAIN	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders GROIN PAIN	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders LIMB DISCOMFORT	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL DISCOMFORT	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders NUCHAL RIGIDITY	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders PAIN IN JAW	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders ROTATOR CUFF SYNDROME	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MALIGNANT PLEURAL EFFUSION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders DYSGEUSIA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders MEMORY IMPAIRMENT	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders TREMOR	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders CEREBROVASCULAR ACCIDENT	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders DIZZINESS POSTURAL	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders DYSAESTHESIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders HYPERAESTHESIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders LETHARGY	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders PERIPHERAL MOTOR NEUROPATHY	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders RESTLESS LEGS SYNDROME	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders SOMNOLENCE	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders ANXIETY	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders CONFUSIONAL STATE	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders DEPRESSION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders POLLAKIURIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders ACUTE KIDNEY INJURY	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders DYSURIA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders MICTURITION URGENCY	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders HAEMATURIA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders NOCTURIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders URINARY TRACT OBSTRUCTION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders URINARY TRACT PAIN	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Reproductive system and breast disorders GYNAECOMASTIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Reproductive system and breast disorders TESTICULAR PAIN	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders DYSPNOEA EXERTIONAL	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders WHEEZING	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders HYPOXIA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders PLEURITIC PAIN	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders PULMONARY OEDEMA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders THROAT IRRITATION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders UPPER-AIRWAY COUGH SYNDROME	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders DERMATITIS ACNEIFORM	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders EXFOLIATIVE RASH	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders NIGHT SWEATS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders PAIN OF SKIN	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders PITYRIASIS RUBRA PILARIS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders PRURITUS GENERALISED	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders RASH FOLLICULAR	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders RASH PRURITIC	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders SKIN REACTION	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders FLUSHING	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders HOT FLUSH	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders PERIPHERAL ARTERY STENOSIS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders VISION BLURRED	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders DIPLOPIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders DRY EYE	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders EPISCLERITIS	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders EYELID PAIN	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders HYPERMETROPIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders PERIORBITAL OEDEMA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders VISUAL ACUITY REDUCED	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders VISUAL IMPAIRMENT	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders VITREOUS DETACHMENT	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders HYPOGLYCAEMIA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 2/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders HYPOKALAEMIA	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders HYPONATRAEMIA	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders HYPERKALAEMIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders HYPERNATRAEMIA	0.00% 0/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders HYPERTRIGLYCERIDAEMIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders HYPOCALCAEMIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders HYPOMAGNESAEMIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders IRON DEFICIENCY	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Ear and labyrinth disorders EAR DISCOMFORT	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Ear and labyrinth disorders EAR PAIN	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Ear and labyrinth disorders HYPOACUSIS	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders EARLY SATIETY	6.7% 2/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.7% 1/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders ASTHENIA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders CHEST PAIN	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders FACE OEDEMA	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders FEELING OF BODY TEMPERATURE CHANGE	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders MALAISE	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders PERIPHERAL SWELLING	3.3% 1/30 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/15 • Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to 3 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Ariad Pharmaceuticals

Phone: +1-844-662-8532

Email: globaloncologymedinfo@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor can review results communications prior to public release and can embargo communications regarding trial results for up to 1 year (to first generate a multicenter publication) and a period that is 60 to 120 days from the time submitted to the sponsor for review. The sponsor can require changes to the communication to delete confidential information, excluding the results of the Study.
• Publication restrictions are in place

Restriction type: OTHER