Trial Outcomes & Findings for A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies (NCT NCT00109707)

NCT ID: NCT00109707

Last Updated: 2021-06-29

Results Overview

Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in bone marrow).

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 507 participants
• Primary outcome timeframe: Up to End of the Treatment (Approximately 7.5 years)
• Results posted on: 2021-06-29

Participant Flow

The study was conducted at 100 centers in 22 countries.

A total of 507 participants were randomized in the core study, out of which 136 participants entered the extension study.

Participant milestones

Measure	CML-CP With Prior Imatinib Only Adult participants PH+ CML-CP ( Chronic Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP Adult participants PH+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Overall Study STARTED	321	137	49
Overall Study Entered Extension Study	106	15	15
Overall Study COMPLETED	67	8	8
Overall Study NOT COMPLETED	254	129	41

Reasons for withdrawal

Measure	CML-CP With Prior Imatinib Only Adult participants PH+ CML-CP ( Chronic Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP Adult participants PH+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Overall Study Discontinued in core study without entering the extension study	215	122	34
Overall Study Abnormal laboratory values	1	0	0
Overall Study Administrative problems	2	0	1
Overall Study Adverse Event	10	2	3
Overall Study Death	4	0	0
Overall Study Disease progression	12	4	3
Overall Study Lost to Follow-up	3	0	0
Overall Study Protocol Violation	1	0	0
Overall Study Patient withdrew consent	6	1	0

Baseline Characteristics

A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies

Baseline characteristics by cohort

Measure	CML-CP With Prior Imatinib Only n=321 Participants Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only n=137 Participants Adult participants PH+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP n=49 Participants Adult participants PH+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Total n=507 Participants Total of all reporting groups
Age, Customized <35 years	22 Participants n=93 Participants	8 Participants n=4 Participants	3 Participants n=27 Participants	33 Participants n=483 Participants
Age, Customized ≥35 to <55 years	104 Participants n=93 Participants	49 Participants n=4 Participants	16 Participants n=27 Participants	169 Participants n=483 Participants
Age, Customized ≥55 to <65 years	97 Participants n=93 Participants	39 Participants n=4 Participants	12 Participants n=27 Participants	148 Participants n=483 Participants
Age, Customized ≥65 years	98 Participants n=93 Participants	41 Participants n=4 Participants	18 Participants n=27 Participants	157 Participants n=483 Participants
Sex: Female, Male Female	159 Participants n=93 Participants	61 Participants n=4 Participants	25 Participants n=27 Participants	245 Participants n=483 Participants
Sex: Female, Male Male	162 Participants n=93 Participants	76 Participants n=4 Participants	24 Participants n=27 Participants	262 Participants n=483 Participants

PRIMARY outcome

Timeframe: Up to End of the Treatment (Approximately 7.5 years)

Population: Full Analysis Set (FAS): All participants who received at least one dose of study medication

Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in bone marrow).

Outcome measures

Measure	CML-CP With Prior Imatinib Only n=321 Participants Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only n=137 Participants Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP n=49 Participants Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Number of Participants With Major Cytogenetic Response (MCyR)	191 Participants	44 Participants	22 Participants

PRIMARY outcome

Timeframe: Up to End of the Treatment (Approximately 7.5 years)

Population: Full Analysis Set (FAS): All participants who received at least one dose of study medication.

Hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes < 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).

Hematological response was a primary outcome measure for Arm CML-AP with prior imatinib only.

Outcome measures

Measure	CML-CP With Prior Imatinib Only n=137 Participants Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Number of Participants Confirmed Overall Hematological Response (Phase II)	76 Participants	—	—

SECONDARY outcome

Timeframe: Up to End of the Treatment (Approximately 7.5 years)

Population: Full Analysis Set (FAS): All participants who received at least one dose of study medication

Cytogenetic responses (CyRs) in CML are based on the percentage of Ph+ metaphases in bone marrow; a value of 0% Ph+ metaphases defines a complete cytogenetic response (CCyR) and >0% to 35% defines a major cytogenetic response (MCyR). Achievement of CCyR is associated with a significant survival advantage in participants with CML-CP. MCyR was categorized as either CCyR or partial cytogenetic response (PCyR).

Outcome measures

Measure	CML-CP With Prior Imatinib Only n=321 Participants Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only n=137 Participants Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP n=49 Participants Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Number of Participants With Overall Major Cytogenetic Responses (Phase II)	191 participants	44 participants	22 participants

SECONDARY outcome

Timeframe: Up to End of the Treatment (Approximately 7.5 years)

Population: Full Analysis Set (FAS): All participants who received at least one dose of study medication

A Complete Hematologic Response (CHR) is obtained when all the following criteria are met: WBC ≤ institutional ULN; platelets ≤ 450,000/mm3; ≤20% basophils in peripheral blood; no blasts or promyelocytes in PB cells; < 5% myelocytes plus metamyelocytes in PB cells; no extra-medullary involvement including no hepatomegaly or splenomegaly.

Outcome measures

Measure	CML-CP With Prior Imatinib Only n=321 Participants Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only n=137 Participants Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP n=35 Participants Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Number of Participants With Complete Hematologic Response (Phase II)	158 participants	76 participants	27 participants

SECONDARY outcome

Timeframe: Up to End of the Treatment (Approximately 7.5 years)

Population: Full Analysis Set (FAS): All participants who received at least one dose of study medication. Major molecular response was not an efficacy variable for participants who received the CML-CP with prior imatinib and other TKI (Group B E8)

MMR was defined for participants who demonstrated a reduction in BCR-ABL/control gene % transcripts to ≤0.1% based on international scale. The control gene used may have been either BCR or ABL.

Outcome measures

Measure	CML-CP With Prior Imatinib Only n=299 Participants Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only n=122 Participants Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Participants With (MMR) Major Molecular Response (Phase II)	106 Participants	18 Participants	—

SECONDARY outcome

Timeframe: Up to End of the Treatment (Approximately 7.5 years)

Population: Full Analysis Set (FAS): All participants who received at least one dose of study medication. Time to progression was not an efficacy variable for participants who received the CML-CP with prior imatinib and other TKI (Group B E8).

Time to Progression was defined as the time from the start of nilotinib to the earliest date of Disease Progression (PD), discontinuation due to PD or death.

Disease progression was defined as an increase in the number of circulating leukemic cells via cytogenetic assessment using real-time quantitative reverse transcriptase polymerase chain reaction (PCR).

Outcome measures

Measure	CML-CP With Prior Imatinib Only n=321 Participants Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only n=137 Participants Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Time to Progression (TTP) (Phase II)	55.6 Months Interval 0.1 to 77.8	15.9 Months Interval 0.1 to 75.7	—

SECONDARY outcome

Timeframe: Up to End of the Treatment (Approximately 7.5 years)

Population: Full Analysis Set (FAS): All participants who received at least one dose of study medication.

OS was calculated for all participants as the time between the start of nilotinib and death. Participants were followed for survival after discontinuation, every 3 months, and were included in the analysis of OS. Censoring was at the date of the last contact for discontinued participants and followed up for survival.

Outcome measures

Measure	CML-CP With Prior Imatinib Only n=321 Participants Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only n=137 Participants Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP n=49 Participants Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Overall Survival (OS) (Phase II)	NA months Interval 77.93 to Median OS was not reached as there were an insufficient number of participants	47.54 months Interval 38.24 to 64.3	NA months Median OS was not reached as there were an insufficient number of participants

SECONDARY outcome

Timeframe: From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years)

Population: Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.

Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.

Outcome measures

Measure	CML-CP With Prior Imatinib Only n=321 Participants Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only n=137 Participants Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP n=49 Participants Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Number of Participants With Adverse Events and Serious Adverse Events to Evaluate Long Term Safety Serious Adverse Events	61 Participants	26 Participants	5 Participants
Number of Participants With Adverse Events and Serious Adverse Events to Evaluate Long Term Safety Adverse Events	57 Participants	17 Participants	7 Participants

Adverse Events

CML-CP With Prior Imatinib Only

Serious events: 146 serious events

Other events: 319 other events

Deaths: 13 deaths

CML-AP With Prior Imatinib Only

Serious events: 55 serious events

Other events: 136 other events

Deaths: 14 deaths

CML-CP

Serious events: 21 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Measure	CML-CP With Prior Imatinib Only n=321 participants at risk Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only n=137 participants at risk Adult participants Ph+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP n=49 participants at risk Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Blood and lymphatic system disorders Thrombocytopenia	3.4% 11/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.0% 11/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Neutropenia	2.2% 7/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.8% 8/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Anaemia	1.2% 4/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.2% 3/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Febrile neutropenia	1.2% 4/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.2% 3/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	4.1% 2/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Angina pectoris	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	1.5% 2/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Myocardial infarction	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Acute myocardial infarction	1.9% 6/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Atrial fibrillation	1.6% 5/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Coronary artery disease	1.6% 5/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Acute coronary syndrome	0.93% 3/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Palpitations	0.93% 3/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Cardiac failure congestive	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Coronary artery stenosis	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Pericardial effusion	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Pericarditis	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Ear and labyrinth disorders Vertigo	0.93% 3/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Eye disorders Catarac	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Eye disorders Diplopia	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Pancreatitis	1.9% 6/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Abdominal pain	1.2% 4/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.2% 3/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Vomiting	0.93% 3/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Diarrhoea	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	1.5% 2/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
General disorders Pyrexia	2.8% 9/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	4.4% 6/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	4.1% 2/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
General disorders Chest pain	1.2% 4/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
General disorders Malaise	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Hepatobiliary disorders Cholelithiasis	0.93% 3/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Lower respiratory tract infection	1.2% 4/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Cellulitis	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Peritonitis	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Pneumonia	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.2% 4/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Sepsis	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Urinary tract infection	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Injury, poisoning and procedural complications Subdural haemorrhage	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Lipase increased	0.93% 3/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	1.5% 2/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Metabolism and nutrition disorders Hyperglycaemia	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Back pain	1.2% 4/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Bone pain	1.2% 4/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.2% 3/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Pain in extremity	1.2% 4/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Arthralgia	0.93% 3/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Muscular weakness	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Cerebrovascular accident	1.2% 4/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Dizziness	1.2% 4/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Brain oedema	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Cerebral infarction	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Cerebral ischaemia	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Headache	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Loss of consciousness	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Peripheral sensory neuropathy	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Presyncope	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Renal and urinary disorders Renal failure	0.93% 3/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.6% 5/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.2% 3/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.2% 4/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Vascular disorders Deep vein thrombosis	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Vascular disorders Haematoma	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Vascular disorders Temporal arteritis	0.62% 2/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.9% 4/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Leukopenia	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	1.5% 2/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Cardiac arrest	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	1.5% 2/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Nausea	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	1.5% 2/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
General disorders Asthenia	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations White blood cell count increased	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.2% 3/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	4.1% 2/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	1.5% 2/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Cerebral haemorrhage	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.2% 3/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Aphasia	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	1.5% 2/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Syncope	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	1.5% 2/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	1.5% 2/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	1.5% 2/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Atrial flutter	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Gastric ulcer	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Abdominal abscess	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Erysipelas	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Herpes zoster	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Injury, poisoning and procedural complications Nerve injury	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Electrocardiogram QT prolonged	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Haemoglobin decreased	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Metabolism and nutrition disorders Dehydration	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostatic adenoma	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Renal and urinary disorders Urinary retention	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 5/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Skin necrosis	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.

Other adverse events

Measure	CML-CP With Prior Imatinib Only n=321 participants at risk Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-AP With Prior Imatinib Only n=137 participants at risk Adult participants Ph+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	CML-CP n=49 participants at risk Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Blood and lymphatic system disorders Leukocytosis	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.6% 9/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Stomatitis	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 14/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Haemorrhoids	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Thrombocytopenia	33.3% 107/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	43.8% 60/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	32.7% 16/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Anaemia	22.1% 71/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	44.5% 61/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	18.4% 9/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Neutropenia	17.8% 57/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	28.5% 39/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	30.6% 15/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Leukopenia	5.0% 16/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.0% 11/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Thrombocytosis	5.0% 16/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Eye disorders Conjunctivitis	6.2% 20/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Nausea	37.7% 121/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	29.9% 41/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	26.5% 13/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Diarrhoea	29.0% 93/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	24.8% 34/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	12.2% 6/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Vomiting	28.7% 92/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	21.9% 30/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	14.3% 7/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Constipation	27.4% 88/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	22.6% 31/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	20.4% 10/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Abdominal pain	14.6% 47/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	12.4% 17/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	16.3% 8/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Abdominal pain upper	14.3% 46/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	15.3% 21/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	12.2% 6/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Gastrointestinal disorders Dyspepsia	10.3% 33/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	14.3% 7/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
General disorders Fatigue	32.7% 105/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	20.4% 28/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	26.5% 13/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
General disorders Pyrexia	20.6% 66/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	35.8% 49/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	16.3% 8/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
General disorders Oedema peripheral	17.1% 55/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	19.7% 27/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 5/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
General disorders Asthenia	16.5% 53/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	17.5% 24/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	24.5% 12/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
General disorders Chest pain	5.9% 19/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.2% 4/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
General disorders Pain	5.9% 19/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	7.3% 10/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.2% 4/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.2% 4/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Nasopharyngitis	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	16.3% 8/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Upper respiratory tract infection	12.8% 41/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 5/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Urinary tract infection	8.7% 28/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.2% 4/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Bronchitis	8.1% 26/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.2% 4/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Sinusitis	6.9% 22/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 5/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Influenza	6.5% 21/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Rhinitis	5.0% 16/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Injury, poisoning and procedural complications Procedural pain	5.3% 17/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Lipase increased	17.1% 55/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.8% 8/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	20.4% 10/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Alanine aminotransferase increased	12.1% 39/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 14/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	16.3% 8/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Weight decreased	9.3% 30/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.9% 15/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	4.1% 2/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Blood bilirubin increased	9.0% 29/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 14/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.2% 4/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Aspartate aminotransferase increased	7.5% 24/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 5/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Blood creatine phosphokinase increased	5.9% 19/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Gamma-glutamyltransferase increased	5.9% 19/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Amylase increased	5.6% 18/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Metabolism and nutrition disorders Decreased appetite	15.6% 50/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.8% 12/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	14.3% 7/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Metabolism and nutrition disorders Hyperglycaemia	8.4% 27/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.8% 12/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Metabolism and nutrition disorders Hypokalaemia	7.8% 25/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	16.1% 22/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	12.2% 6/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Metabolism and nutrition disorders Hypophosphataemia	6.9% 22/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	7.3% 10/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 5/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Metabolism and nutrition disorders Hypomagnesaemia	5.9% 19/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	7.3% 10/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Metabolism and nutrition disorders Hypocalcaemia	5.3% 17/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.9% 15/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Arthralgia	26.8% 86/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	14.6% 20/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	20.4% 10/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Myalgia	19.6% 63/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	14.3% 7/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Pain in extremity	19.6% 63/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	13.1% 18/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	18.4% 9/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Back pain	18.7% 60/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	13.9% 19/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	14.3% 7/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Muscle spasms	14.0% 45/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.6% 9/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	16.3% 8/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Bone pain	13.4% 43/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 14/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.2% 4/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	10.0% 32/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Neck pain	5.0% 16/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Headache	35.5% 114/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	22.4% 11/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Dizziness	10.9% 35/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 5/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Nervous system disorders Paraesthesia	5.3% 17/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Psychiatric disorders Insomnia	12.5% 40/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	4.1% 2/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Psychiatric disorders Depression	8.7% 28/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Psychiatric disorders Anxiety	6.2% 20/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Renal and urinary disorders Pollakiuria	5.3% 17/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Cough	28.3% 91/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	15.3% 21/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.9% 51/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 14/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	18.4% 9/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.1% 39/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	11.7% 16/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	4.1% 2/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	6.5% 21/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.0% 16/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	12.4% 17/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	4.1% 2/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Rash	36.8% 118/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	28.5% 39/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	40.8% 20/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Pruritus	32.4% 104/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	13.1% 18/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	18.4% 9/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Night sweats	11.5% 37/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Dry skin	11.2% 36/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.2% 4/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Alopecia	10.6% 34/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.8% 8/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Erythema	9.3% 30/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.2% 4/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Hyperhidrosis	8.1% 26/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Skin lesion	5.9% 19/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Vascular disorders Hypertension	11.5% 37/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 5/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Tachycardia	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
General disorders Chills	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.9% 15/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Pneumonia	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations White blood cell count decreased	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.0% 11/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Haemoglobin decreased	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Platelet count decreased	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	5.1% 7/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	7.3% 10/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.2% 4/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.6% 9/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Vascular disorders Haematoma	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	7.3% 10/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Vascular disorders Hypotension	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	7.3% 10/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	2.0% 1/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Cardiac disorders Ventricular extrasystoles	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
General disorders Inflammation	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Herpes simplex	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Herpes zoster	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Infections and infestations Periodontitis	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Weight increased	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	10.2% 5/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Investigations Blood glucose increased	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	8.2% 4/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/321 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	0.00% 0/137 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.	6.1% 3/49 • From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.

Additional Information

Study Director

NovartisPharmaceuticals

Phone: 862-778-8300

Email: novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER