Trial Outcomes & Findings for Dose Escalation Study of MLN0128 in Participants With Advanced Malignancies (NCT NCT01058707)

NCT ID: NCT01058707

Last Updated: 2020-04-01

Results Overview

MTD was defined as the highest dose level of MLN0128 at which no more than 1 out of 6 evaluable participants experienced a DLT during the first cycle (28 days) of therapy.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 198 participants
• Primary outcome timeframe: Cycle 1 (28 Days)
• Results posted on: 2020-04-01

Participant Flow

Participants took part in the study at 15 investigative sites in Spain and the United States from 4 January 2010 to 7 February 2019.

Participants with a diagnosis of advanced malignancies were enrolled and received rising doses of MLN0128 in the Dose Escalation Phase to determine Maximum Tolerated Dose (MTD). In the Dose Expansion Phase participants were enrolled to receive one of 3 dose regimens: MLN0128 5 mg once daily (QD), 30 mg once weekly (QW) or 40 mg QW.

Participant milestones

Measure	MLN0128 QD MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).
Overall Study STARTED	31	30	33	22	39	17	26
Overall Study COMPLETED	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	31	30	33	22	39	17	26

Reasons for withdrawal

Measure	MLN0128 QD MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).
Overall Study Adverse Event	11	4	7	6	7	3	1
Overall Study Subject Decision	5	3	3	1	2	3	6
Overall Study Lost to Follow-up	0	0	1	0	0	0	0
Overall Study Disease Progression	15	20	20	15	23	10	12
Overall Study Reason Not Specified	0	3	2	0	7	1	7

Baseline Characteristics

Dose Escalation Study of MLN0128 in Participants With Advanced Malignancies

Baseline characteristics by cohort

Measure	MLN0128 QD n=31 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=30 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=33 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=22 Participants MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD n=39 Participants MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW n=17 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=26 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	Total n=198 Participants Total of all reporting groups
Age, Continuous	59.7 years n=5 Participants	53.8 years n=7 Participants	56.1 years n=5 Participants	58.1 years n=4 Participants	58.8 years n=21 Participants	59.7 years n=10 Participants	63.2 years n=115 Participants	58.31 years n=6 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	18 Participants n=7 Participants	22 Participants n=5 Participants	13 Participants n=4 Participants	16 Participants n=21 Participants	6 Participants n=10 Participants	14 Participants n=115 Participants	105 Participants n=6 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	12 Participants n=7 Participants	11 Participants n=5 Participants	9 Participants n=4 Participants	23 Participants n=21 Participants	11 Participants n=10 Participants	12 Participants n=115 Participants	93 Participants n=6 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants	11 Participants n=7 Participants	7 Participants n=5 Participants	9 Participants n=4 Participants	8 Participants n=21 Participants	1 Participants n=10 Participants	2 Participants n=115 Participants	49 Participants n=6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	19 Participants n=7 Participants	26 Participants n=5 Participants	13 Participants n=4 Participants	30 Participants n=21 Participants	16 Participants n=10 Participants	24 Participants n=115 Participants	148 Participants n=6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=6 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	2 Participants n=6 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	6 Participants n=6 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	29 Participants n=7 Participants	30 Participants n=5 Participants	22 Participants n=4 Participants	37 Participants n=21 Participants	17 Participants n=10 Participants	25 Participants n=115 Participants	188 Participants n=6 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	1 Participants n=6 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=6 Participants
Region of Enrollment United States	21 Participants n=5 Participants	18 Participants n=7 Participants	19 Participants n=5 Participants	12 Participants n=4 Participants	32 Participants n=21 Participants	15 Participants n=10 Participants	25 Participants n=115 Participants	142 Participants n=6 Participants
Region of Enrollment Spain	10 Participants n=5 Participants	12 Participants n=7 Participants	14 Participants n=5 Participants	10 Participants n=4 Participants	7 Participants n=21 Participants	2 Participants n=10 Participants	1 Participants n=115 Participants	56 Participants n=6 Participants

PRIMARY outcome

Timeframe: Cycle 1 (28 Days)

Population: Dose Escalation-Evaluable Population included participants who received ≥ 75% or more of planned doses of MLN0128 in Cycle 1 or stopped study drug before receiving 75% of doses because of study drug-related AEs considered a DLT.

MTD was defined as the highest dose level of MLN0128 at which no more than 1 out of 6 evaluable participants experienced a DLT during the first cycle (28 days) of therapy.

Outcome measures

Measure	MLN0128 QD n=25 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=27 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=29 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=22 Participants MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
Dose Escalation Phase: Maximum Tolerated Dose (MTD)	6 milligrams (mg)	40 milligrams (mg)	9 milligrams (mg)	7 milligrams (mg)	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 (28 days)

Population: Dose Escalation-Evaluable Population included participants who received ≥ 75% or more of planned doses of MLN0128 in Cycle 1 or stopped study drug before receiving 75% of doses because of study drug-related AEs considered a DLT.

DLTs were defined as MLN0128-related treatment-emergent adverse events (TEAEs) that occurred within the Cycle 1 (first 28 days of treatment) as per Common Terminology Criteria for Adverse Events (CTCAE): Any ≥Grade 3 or non-hematologic toxicity except for Grade 3 nausea and/or vomiting and diarrhea, Grade 3 hyperglycemia lasting ≤ 14 days, Grade 3 rash lasting ≤ 3 days; Grade 4 neutropenia lasting >7 days in the absence of growth factor support; Grade 4 neutropenia of any duration associated with fever ≥38.5 degree celsius and/or systemic infection; Any other Grade 4 hematologic toxicity; Inability to administer at least 75% of planned doses of MLN0128 within Cycle 1 due to drug-related toxicity and any clinically significant occurrence that the investigators and sponsor agreed would place participants at an undue safety risk.

Outcome measures

Measure	MLN0128 QD n=25 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=27 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=29 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=22 Participants MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
Dose Escalation Phase: Number of Participants With Dose Limiting Toxicities (DLTs)	7 Participants	2 Participants	6 Participants	7 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: First dose of study drug through 30 days after the administration of the last dose of study drug (Up to approximately 244 weeks)

Population: ASaT population included all participants who received at least 1 dose of MLN0128.

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Measure	MLN0128 QD n=31 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=30 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=33 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=22 Participants MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD n=39 Participants MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW n=17 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=26 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
Number of Participants Experiencing One or More Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Resulting in Discontinuation of MLN0128 and Fatal AEs Within 30 Days of Last Dose of Study Drug TEAE	31 Participants	30 Participants	33 Participants	22 Participants	39 Participants	17 Participants	26 Participants	—	—	—	—	—	—	—	—	—	—	—
Number of Participants Experiencing One or More Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Resulting in Discontinuation of MLN0128 and Fatal AEs Within 30 Days of Last Dose of Study Drug SAE	13 Participants	10 Participants	17 Participants	10 Participants	19 Participants	6 Participants	9 Participants	—	—	—	—	—	—	—	—	—	—	—
Number of Participants Experiencing One or More Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Resulting in Discontinuation of MLN0128 and Fatal AEs Within 30 Days of Last Dose of Study Drug AEs Resulting in Discontinuation of MLN0128	11 Participants	4 Participants	7 Participants	6 Participants	7 Participants	3 Participants	2 Participants	—	—	—	—	—	—	—	—	—	—	—
Number of Participants Experiencing One or More Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Resulting in Discontinuation of MLN0128 and Fatal AEs Within 30 Days of Last Dose of Study Drug Fatal AEs within 30 Days of Last Dose Study Drug	1 Participants	1 Participants	2 Participants	0 Participants	0 Participants	2 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From the first dose of study drug up to disease progression or death (Up to approximately 240 weeks)

Population: Response-Evaluable Population included participants who received at least 1 dose of MLN0128, had measurable disease at Baseline, and underwent at least 1 post-Baseline disease assessment. Participants without a post-Baseline disease assessment but discontinued study drug due to symptomatic and/or clinical deterioration were included.

ORR is defined as the percentage of participants who achieved complete response (CR) or partial response (PR based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. CR is defined as disappearance of all target lesions and PR was defined of at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD and for non-target lesions. Data was categorized as per type of cancer.

Outcome measures

Measure	MLN0128 QD n=36 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=14 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=22 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
Dose Expansion: Objective Response Rate (ORR) Cancer Type: Renal	15 percentage of participants	13 percentage of participants	15 percentage of participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dose Expansion: Objective Response Rate (ORR) Cancer Type: Endometrial	9 percentage of participants	0 percentage of participants	0 percentage of participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dose Expansion: Objective Response Rate (ORR) Cancer Type: Bladder	0 percentage of participants	0 percentage of participants	0 percentage of participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From the first dose of study drug up to disease progression or death (Up to approximately 240 weeks)

Population: Response-Evaluable Population:participants who received ≥1 dose of MLN0128,had measurable disease at Baseline,had ≥1 post-Baseline disease assessment.Participants without post-Baseline disease assessment but discontinued study drug due to symptomatic and/or clinical deterioration were included.CR/PR participants with available data were analyzed.

Duration of objective response is defined as the number of months from the start date of CR or PR (whichever occurred first) based on RECIST Criteria version 1.1 to the first date of objectively documented progressive disease (PD) for participants who achieved CR or PR. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

Outcome measures

Measure	MLN0128 QD n=4 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=1 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=2 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
Dose Expansion Phase: Duration of Objective Response	8.90 months Interval 3.48 to 23.06	56.05 months Interval 56.05 to 56.05	20.73 months Interval 20.24 to 21.22	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From the first dose of study drug up to disease progression or death (Up to approximately 240 weeks)

Population: Response-Evaluable Population: participants who received ≥1 dose of MLN0128, had measurable disease at Baseline (BL), underwent ≥1 post-BL disease assessment. Participants without post-BL disease assessment but discontinued study drug due to symptomatic and/or clinical deterioration were included. SD participants with available data were analyzed.

Duration of SD was evaluated for participants with best response of SD and is defined as number of months from date of first dose to date of PD. As per RECIST 1.1, SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PR was defined of at least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD and for non-target lesions. PD is defined as at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this includes baseline sum if that is smallest on study).

Outcome measures

Measure	MLN0128 QD n=19 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=5 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=11 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
Dose Expansion: Duration of Stable Disease (SD)	3.68 months Interval 0.95 to 14.88	2.20 months Interval 0.76 to 5.45	3.55 months Interval 1.18 to 13.08	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose and multiple time-points up to 8 hours post-dose on Day 1 of Cycles 1 and 2

Population: Pharmacokinetic (PK) population consisted of all participants included during the dose escalation phase of the study who received at least 1 dose of MLN0128. Number analyzed is the number of participants with data available for analysis at the given time-point.

Outcome measures

Measure	MLN0128 QD n=3 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=7 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=12 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=8 Participants MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD n=3 Participants MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW n=3 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=3 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW n=3 Participants MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW n=3 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=15 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW n=3 Participants MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW n=8 Participants MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW n=6 Participants MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW n=11 Participants MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW n=4 Participants MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW n=6 Participants MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW n=11 Participants MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW n=3 Participants MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
Cmax: Maximum Observed Plasma Concentration for MLN0128 Cycle 1 Day 1	13.7 ng/mL Interval 12.3 to 16.3	20.5 ng/mL Interval 9.54 to 35.7	48.9 ng/mL Interval 18.6 to 75.6	67.8 ng/mL Interval 21.1 to 143.0	43.6 ng/mL Interval 16.2 to 94.4	75.9 ng/mL Interval 43.6 to 139.0	80.2 ng/mL Interval 24.3 to 173.0	136.6 ng/mL Interval 66.8 to 217.0	174.0 ng/mL Interval 101.0 to 259.0	193.8 ng/mL Interval 57.9 to 358.0	88.5 ng/mL Interval 72.9 to 115.0	82.9 ng/mL Interval 25.0 to 111.0	124.3 ng/mL Interval 50.9 to 320.0	78.5 ng/mL Interval 35.2 to 184.0	194.0 ng/mL Interval 118.0 to 300.0	46.9 ng/mL Interval 18.8 to 79.0	48.5 ng/mL Interval 22.6 to 76.5	110.1 ng/mL Interval 42.3 to 181.0
Cmax: Maximum Observed Plasma Concentration for MLN0128 Cycle 2 Day 1	16.2 ng/mL Interval 12.0 to 22.7	22.1 ng/mL Interval 11.9 to 35.9	39.4 ng/mL Interval 24.0 to 76.4	65.0 ng/mL Interval 28.2 to 130.0	66.7 ng/mL Interval 55.8 to 77.6	40.5 ng/mL Interval 22.4 to 58.5	66.9 ng/mL Interval 47.7 to 87.9	134.00 ng/mL Interval 134.0 to 134.0	142.6 ng/mL Interval 96.7 to 222.0	249.8 ng/mL Interval 140.0 to 394.0	60.0 ng/mL Interval 52.5 to 74.4	87.7 ng/mL Interval 46.8 to 118.0	115.1 ng/mL Interval 93.4 to 143.0	113.6 ng/mL Interval 42.5 to 292.0	183.00 ng/mL Interval 183.0 to 183.0	60.1 ng/mL Interval 23.5 to 126.0	60.0 ng/mL Interval 32.0 to 95.7	96.50 ng/mL Interval 96.5 to 96.5

SECONDARY outcome

Timeframe: Pre-dose and multiple time-points up to 8 hours post-dose on Day 1 of Cycles 1 and 2

Population: PK population consisted of all participants included during the dose escalation phase of the study who received at least 1 dose of MLN0128. Number analyzed is the number of participants with data available for analysis at the given time-point.

Outcome measures

Measure	MLN0128 QD n=3 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=7 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=12 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=8 Participants MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD n=3 Participants MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW n=3 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=3 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW n=3 Participants MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW n=3 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=15 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW n=3 Participants MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW n=8 Participants MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW n=6 Participants MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW n=11 Participants MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW n=4 Participants MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW n=6 Participants MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW n=11 Participants MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW n=3 Participants MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
Ctrough: Observed Concentration at the End of a Dosing Interval Cycle 1 Day 1	0.9 ng/mL Interval 0.0 to 2.76	1.2 ng/mL Interval 0.0 to 2.48	3.5 ng/mL Interval 0.0 to 8.84	4.4 ng/mL Interval 1.15 to 9.22	—	—	—	—	—	—	2.5 ng/mL Interval 0.0 to 5.01	6.8 ng/mL Interval 0.0 to 16.8	9.9 ng/mL Interval 1.83 to 22.9	8.1 ng/mL Interval 0.0 to 21.5	44.7 ng/mL Interval 6.35 to 123.0	3.1 ng/mL Interval 2.02 to 4.48	3.6 ng/mL Interval 0.0 to 10.1	21.7 ng/mL Interval 5.85 to 43.7
Ctrough: Observed Concentration at the End of a Dosing Interval Cycle 2 Day 1	4.5 ng/mL Interval 1.48 to 9.76	3.7 ng/mL Interval 0.0 to 10.3	4.5 ng/mL Interval 3.07 to 9.37	3.0 ng/mL Interval 1.24 to 6.23	—	—	—	—	—	—	10.3 ng/mL Interval 0.0 to 25.1	10.8 ng/mL Interval 5.03 to 25.5	4.4 ng/mL Interval 3.34 to 5.38	10.0 ng/mL Interval 0.0 to 27.1	11.40 ng/mL Interval 11.4 to 11.4	5.2 ng/mL Interval 1.82 to 11.2	3.0 ng/mL Interval 1.08 to 4.68	6.58 ng/mL Interval 6.58 to 6.58

SECONDARY outcome

Timeframe: Pre-dose and multiple time-points up to 8 hours post-dose on Day 1 of Cycles 1 and 2

Population: PK population consisted of all participants included during the dose escalation phase of the study who received at least 1 dose of MLN0128. Number analyzed is the number of participants with data available for analysis at the given time-point.

Outcome measures

Measure	MLN0128 QD n=3 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=7 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=12 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=8 Participants MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD n=3 Participants MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW n=3 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=3 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW n=3 Participants MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW n=3 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=15 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW n=3 Participants MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW n=8 Participants MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW n=6 Participants MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW n=11 Participants MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW n=4 Participants MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW n=6 Participants MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW n=11 Participants MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW n=3 Participants MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
Terminal Phase Elimination Half-life (T1/2) for MLN0128 Cycle 1 Day 1	10.3 hours Interval 10.3 to 10.3	7.4 hours Interval 5.27 to 8.22	6.3 hours Interval 4.86 to 10.4	6.2 hours Interval 5.66 to 6.23	6.47 hours Interval 6.47 to 6.47	5.8 hours Interval 5.72 to 5.95	9.4 hours Interval 6.99 to 11.9	5.7 hours Interval 4.11 to 11.6	5.5 hours Interval 5.3 to 6.94	7.1 hours Interval 4.07 to 12.7	5.5 hours Interval 5.15 to 5.93	7.9 hours Interval 6.53 to 8.12	6.4 hours Interval 4.71 to 11.1	7.2 hours Interval 4.59 to 9.52	5.5 hours Interval 5.1 to 5.84	7.8 hours Interval 5.26 to 9.38	6.5 hours Interval 4.72 to 10.1	8.7 hours Interval 8.2 to 9.16
Terminal Phase Elimination Half-life (T1/2) for MLN0128 Cycle 2 Day 1	8.1 hours Interval 7.49 to 8.75	9.7 hours Interval 9.47 to 11.7	7.9 hours Interval 5.83 to 8.06	4.9 hours Interval 3.99 to 7.85	5.6 hours Interval 4.91 to 6.19	—	8.01 hours Interval 8.01 to 8.01	4.57 hours Interval 4.57 to 4.57	5.7 hours Interval 5.08 to 6.35	5.6 hours Interval 4.29 to 9.02	9.1 hours Interval 6.05 to 12.1	7.0 hours Interval 6.01 to 7.85	4.9 hours Interval 4.63 to 5.11	6.4 hours Interval 3.61 to 10.3	6.28 hours Interval 6.28 to 6.28	6.8 hours Interval 6.18 to 7.14	5.6 hours Interval 4.19 to 7.58	6.42 hours Interval 6.42 to 6.42

SECONDARY outcome

Timeframe: Pre-dose and multiple time-points up to 8 hours post-dose on Day 1 of Cycles 1 and 2

Population: PK population consisted of all participants included during the dose escalation phase of the study who received at least 1 dose of MLN0128. Number analyzed is the number of participants with data available for analysis at the given time-point.

Outcome measures

Measure	MLN0128 QD n=3 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=7 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=12 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=8 Participants MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD n=3 Participants MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW n=3 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=3 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW n=3 Participants MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW n=3 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=15 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW n=3 Participants MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW n=8 Participants MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW n=6 Participants MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW n=11 Participants MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW n=4 Participants MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW n=6 Participants MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW n=11 Participants MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW n=3 Participants MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN0128 Cycle 1 Day 1	185.00 ng*hr/mL Interval 185.0 to 185.0	205.3 ng*hr/mL Interval 145.0 to 269.0	390.6 ng*hr/mL Interval 263.0 to 608.0	459.5 ng*hr/mL Interval 195.0 to 585.0	440.00 ng*hr/mL Interval 440.0 to 440.0	609.0 ng*hr/mL Interval 241.0 to 977.0	1014.5 ng*hr/mL Interval 179.0 to 1850.0	1172.7 ng*hr/mL Interval 563.0 to 2190.0	1316.3 ng*hr/mL Interval 759.0 to 2290.0	2149.8 ng*hr/mL Interval 844.0 to 4310.0	494.0 ng*hr/mL Interval 411.0 to 577.0	725.2 ng*hr/mL Interval 388.0 to 903.0	922.8 ng*hr/mL Interval 383.0 to 1470.0	820.1 ng*hr/mL Interval 389.0 to 1220.0	1245.0 ng*hr/mL Interval 1080.0 to 1410.0	326.2 ng*hr/mL Interval 240.0 to 423.0	388.5 ng*hr/mL Interval 231.0 to 761.0	941.5 ng*hr/mL Interval 483.0 to 1400.0
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN0128 Cycle 2 Day 1	—	—	—	—	371.0 ng*hr/mL Interval 354.0 to 388.0	—	510.00 ng*hr/mL Interval 510.0 to 510.0	1030.00 ng*hr/mL Interval 1030.0 to 1030.0	1427.5 ng*hr/mL Interval 745.0 to 2110.0	2876.6 ng*hr/mL Interval 903.0 to 6110.0	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose and multiple time-points up to 8 hours post-dose on Day 1 of Cycles 1 and 2

Population: PK population consisted of all participants included during the dose escalation phase of the study who received at least 1 dose of MLN0128. Number analyzed is the number of participants with data available for analysis at the given time-point.

Outcome measures

Measure	MLN0128 QD n=3 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=7 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=12 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=8 Participants MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD n=3 Participants MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW n=3 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=3 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW n=3 Participants MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW n=3 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=15 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW n=3 Participants MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW n=8 Participants MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW n=6 Participants MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW n=11 Participants MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW n=4 Participants MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW n=6 Participants MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW n=11 Participants MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW n=3 Participants MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN0128 Cycle 1 Day 1	65.4 ng*hr/mL Interval 64.0 to 66.8	65.3 ng*hr/mL Interval 51.6 to 89.8	95.30 ng*hr/mL Interval 95.3 to 95.3	—	72.80 ng*hr/mL Interval 72.8 to 72.8	106.00 ng*hr/mL Interval 106.0 to 106.0	—	—	—	—	162.00 ng*hr/mL Interval 162.0 to 162.0	207.5 ng*hr/mL Interval 198.0 to 217.0	—	130.2 ng*hr/mL Interval 93.4 to 167.0	—	—	221.00 ng*hr/mL Interval 221.0 to 221.0	—
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN0128 Cycle 2 Day 1	—	62.2 ng*hr/mL Interval 56.3 to 68.0	—	—	—	105.00 ng*hr/mL Interval 105.0 to 105.0	—	—	—	—	182.00 ng*hr/mL Interval 182.0 to 182.0	—	—	197.00 ng*hr/mL Interval 197.0 to 197.0	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose and multiple time-points up to 8 hours post-dose on Day 1 of Cycles 1 and 2

Population: PK population consisted of all participants included during the dose escalation phase of the study who received at least 1 dose of MLN0128. Number analyzed is the number of participants with data available for analysis at the given time-point.

Outcome measures

Measure	MLN0128 QD n=3 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=7 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=12 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=8 Participants MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD n=3 Participants MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW n=3 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=3 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW n=3 Participants MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW n=3 Participants MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=15 Participants MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW n=3 Participants MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW n=8 Participants MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW n=6 Participants MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW n=11 Participants MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW n=4 Participants MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW n=6 Participants MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW n=11 Participants MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW n=3 Participants MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
Tmax: Time to Maximum Observed Plasma Concentration for MLN0128 Cycle 1 Day 1	2.0 hours Interval 2.0 to 2.05	2.0 hours Interval 0.98 to 4.0	1.0 hours Interval 0.5 to 4.17	1.5 hours Interval 0.5 to 7.57	2.1 hours Interval 0.52 to 8.0	1.0 hours Interval 1.0 to 1.97	2.0 hours Interval 1.07 to 2.0	2.0 hours Interval 1.0 to 2.15	1.0 hours Interval 1.0 to 4.0	2.4 hours Interval 1.0 to 4.53	0.6 hours Interval 0.5 to 1.15	1.1 hours Interval 0.55 to 4.33	2.0 hours Interval 0.55 to 4.05	2.1 hours Interval 0.5 to 8.67	3.1 hours Interval 0.53 to 4.05	1.2 hours Interval 0.5 to 4.08	4.0 hours Interval 0.53 to 4.33	2.1 hours Interval 1.08 to 8.0
Tmax: Time to Maximum Observed Plasma Concentration for MLN0128 Cycle 2 Day 1	2.0 hours Interval 1.97 to 2.0	3.8 hours Interval 1.0 to 4.03	2.0 hours Interval 1.03 to 4.42	4.0 hours Interval 1.0 to 4.03	1.02 hours Interval 1.02 to 1.02	2.9 hours Interval 1.8 to 4.0	2.0 hours Interval 2.0 to 8.0	4.0 hours Interval 4.0 to 4.0	4.0 hours Interval 1.03 to 7.92	2.0 hours Interval 1.0 to 8.0	4.0 hours Interval 1.0 to 4.0	2.1 hours Interval 0.5 to 7.57	3.7 hours Interval 1.0 to 4.18	2.1 hours Interval 0.53 to 8.0	1.0 hours Interval 1.0 to 1.0	1.5 hours Interval 0.97 to 7.42	2.0 hours Interval 0.52 to 3.58	2.02 hours Interval 2.02 to 2.02

SECONDARY outcome

Timeframe: Pre-dose and multiple time-points up to 8 hours post-dose on Day 1 of Cycles 1 and 2

Population: The study was acquired from another organization and limited results data are available.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Cycle 1 Week 2

Population: ASaT population included all participants who received at least 1 dose of MLN0128 in dose escalation phase. Participants with data at Baseline and Cycle 1 Week 2 are included. Number analyzed is the number of participants with data available at the given time-point.

P4EBP, PAKT and PS6 were assayed in skin biopsies. A negative percentage change from Baseline indicates improvement.

Outcome measures

Measure	MLN0128 QD n=31 Participants MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=30 Participants MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=33 Participants MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=22 Participants MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 20 mg QW MLN0128 20 mg, capsule, orally QW in 28-day cycle (Up to 10.1 weeks).	MLN0128 30 mg QW MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).	MLN0128 6 mg QDx3dQW MLN0128 6 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 8.4 weeks).	MLN0128 9 mg QDx3d QW MLN0128 9 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 129.4 weeks).	MLN0128 12 mg QDx3d QW MLN0128 12 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 11.4 weeks).	MLN0128 16 mg QDx3d QW MLN0128 16 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 31.4 weeks).	MLN0128 20 mg QDx3dQW MLN0128 20 mg, capsule, orally QDx3d QW in 28-day cycle (Up to 7.4 weeks).	MLN0128 7 mg QDx5dQW MLN0128 7 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 15.9 weeks).	MLN0128 10 mg QDx5dQW MLN0128 10 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 161.9 weeks).	MLN0128 13 mg QDx5dQW MLN0128 13 mg, capsule, orally QDx5d QW in 28-day cycle (Up to 7.7 weeks).
Percentage Change From Baseline in Eukaryotic Initiation Factor 4E-binding Protein 1 (P4EBP1), Serine/Threonine Protein Kinase B (PAKT) and Ribosomal Protein S6 (PS6) p4EBP1	-64.1 percentage change Standard Deviation 47.65	-15.5 percentage change Standard Deviation 378.88	-99.5 percentage change Standard Deviation 2.75	87.4 percentage change Standard Deviation 43.83	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Percentage Change From Baseline in Eukaryotic Initiation Factor 4E-binding Protein 1 (P4EBP1), Serine/Threonine Protein Kinase B (PAKT) and Ribosomal Protein S6 (PS6) pAKT	27.1 percentage change Standard Deviation 73.78	26.9 percentage change Standard Deviation 139.75	73.3 percentage change Standard Deviation 115.55	168.9 percentage change Standard Deviation 514.88	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Percentage Change From Baseline in Eukaryotic Initiation Factor 4E-binding Protein 1 (P4EBP1), Serine/Threonine Protein Kinase B (PAKT) and Ribosomal Protein S6 (PS6) pS6	-50.2 percentage change Standard Deviation 43.89	-42.7 percentage change Standard Deviation 59.64	-68.2 percentage change Standard Deviation 37.98	-82.5 percentage change Standard Deviation 12.15	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Adverse Events

MLN0128 QD

Serious events: 13 serious events

Other events: 31 other events

Deaths: 3 deaths

MLN0128 QW

Serious events: 10 serious events

Other events: 30 other events

Deaths: 2 deaths

MLN0128 QDx3d QW

Serious events: 17 serious events

Other events: 33 other events

Deaths: 2 deaths

MLN0128 QDx5d QW

Serious events: 10 serious events

Other events: 22 other events

Deaths: 0 deaths

MLN0128 5 mg QD

Serious events: 19 serious events

Other events: 39 other events

Deaths: 2 deaths

MLN0128 30 mg QW

Serious events: 6 serious events

Other events: 17 other events

Deaths: 2 deaths

MLN0128 40 mg QW

Serious events: 9 serious events

Other events: 26 other events

Deaths: 3 deaths

Serious adverse events

Measure	MLN0128 QD n=31 participants at risk MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=30 participants at risk MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=33 participants at risk MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=22 participants at risk MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD n=39 participants at risk MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW n=17 participants at risk MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=26 participants at risk MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).
Gastrointestinal disorders Stomatitis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.1% 4/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Abdominal pain	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Intestinal obstruction	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Diarrhoea	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Dysphagia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Enterocutaneous fistula	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Nausea	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Oesophagitis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Pancreatitis acute	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Vomiting	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intestinal adenocarcinoma	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Pneumonia	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Bacteraemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Cellulitis	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Device related infection	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Gastroenteritis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Osteomyelitis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Sepsis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Urinary tract infection	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Asthenia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders General physical health deterioration	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Cardiac disorders Atrial fibrillation	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Cardiac disorders Cardiac arrest	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Cardiac disorders Cardiac tamponade	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Cardiac disorders Supraventricular tachycardia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Cardiac disorders Ventricular fibrillation	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Renal and urinary disorders Renal failure	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Renal and urinary disorders Nephrolithiasis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Dehydration	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Injury, poisoning and procedural complications Overdose	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Brain oedema	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Hemiparesis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Seizure	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Blood and lymphatic system disorders Anaemia	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Endocrine disorders Carcinoid syndrome	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Ejection fraction decreased	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Constipation	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Cystitis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Respiratory tract infection	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Renal and urinary disorders Acute kidney injury	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Renal and urinary disorders Haematuria	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Renal and urinary disorders Hydronephrosis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Disease progression	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Fatigue	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Pyrexia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Vascular disorders Deep vein thrombosis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Vascular disorders Hypotension	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Vascular disorders Peripheral ischaemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Psychiatric disorders Delirium	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Psychiatric disorders Mental status changes	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Encephalopathy	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)

Other adverse events

Measure	MLN0128 QD n=31 participants at risk MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks).	MLN0128 QW n=30 participants at risk MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks).	MLN0128 QDx3d QW n=33 participants at risk MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks).	MLN0128 QDx5d QW n=22 participants at risk MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks).	MLN0128 5 mg QD n=39 participants at risk MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks).	MLN0128 30 mg QW n=17 participants at risk MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks).	MLN0128 40 mg QW n=26 participants at risk MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks).
Skin and subcutaneous tissue disorders Pruritus generalised	32.3% 10/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	18.2% 6/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	30.8% 12/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	29.4% 5/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Flatulence	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Ascites	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Retching	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Tongue ulceration	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Pruritus	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.0% 3/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	18.2% 4/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	25.6% 10/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.4% 4/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Nausea	51.6% 16/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	73.3% 22/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	72.7% 24/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	59.1% 13/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	53.8% 21/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	70.6% 12/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	76.9% 20/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Vomiting	38.7% 12/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	66.7% 20/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	60.6% 20/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	54.5% 12/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	30.8% 12/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	52.9% 9/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	76.9% 20/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Stomatitis	35.5% 11/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	33.3% 10/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	66.7% 22/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	59.1% 13/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	48.7% 19/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	52.9% 9/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	42.3% 11/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Diarrhoea	45.2% 14/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	33.3% 10/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	51.5% 17/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	40.9% 9/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	51.3% 20/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	52.9% 9/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	42.3% 11/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Dry mouth	25.8% 8/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	23.3% 7/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.8% 5/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	17.6% 3/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	26.9% 7/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Abdominal pain	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	20.0% 6/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.1% 4/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	18.2% 4/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	20.5% 8/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	35.3% 6/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.4% 4/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Constipation	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	20.0% 6/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	18.2% 6/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.6% 3/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	25.6% 10/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	47.1% 8/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	38.5% 10/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Abdominal pain upper	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Abdominal distension	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	17.6% 3/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Dyspepsia	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	17.6% 3/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Oral pain	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	19.2% 5/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Abdominal discomfort	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Haemorrhoids	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hyperglycaemia	83.9% 26/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	60.0% 18/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	66.7% 22/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	54.5% 12/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	46.2% 18/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	70.6% 12/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	76.9% 20/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Decreased appetite	41.9% 13/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	40.0% 12/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	60.6% 20/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	40.9% 9/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	51.3% 20/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	41.2% 7/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	53.8% 14/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Dehydration	16.1% 5/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	20.0% 6/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	18.2% 6/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	17.9% 7/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	23.5% 4/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	19.2% 5/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hypokalaemia	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.3% 4/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	22.7% 5/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.4% 6/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	17.6% 3/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hypercholesterolaemia	16.1% 5/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.1% 4/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hypomagnesaemia	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.0% 3/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.1% 4/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.6% 3/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.3% 4/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hyponatraemia	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.1% 4/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hypocalcaemia	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hypocholesterolaemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Asthenia	22.6% 7/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	50.0% 15/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	39.4% 13/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	45.5% 10/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	17.9% 7/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	19.2% 5/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Fatigue	32.3% 10/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	30.0% 9/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	45.5% 15/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	31.8% 7/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	64.1% 25/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	64.7% 11/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	92.3% 24/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Pyrexia	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	30.0% 9/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	24.2% 8/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	27.3% 6/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	20.5% 8/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	19.2% 5/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Chills	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.0% 3/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Oedema peripheral	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.3% 4/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	23.1% 9/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	19.2% 5/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Chest pain	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Performance status decreased	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Headache	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	26.7% 8/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	27.3% 9/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	22.7% 5/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.3% 4/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	17.6% 3/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	23.1% 6/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Dysgeusia	29.0% 9/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.3% 4/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.1% 4/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	18.2% 4/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	25.6% 10/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	23.5% 4/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Dizziness	12.9% 4/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.0% 3/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.2% 5/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	23.1% 9/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Tremor	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.6% 3/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Neuropathy peripheral	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Somnolence	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Hypoaesthesia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Rash	32.3% 10/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.3% 4/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	21.2% 7/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	18.2% 4/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Rash pruritic	12.9% 4/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Dry skin	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.6% 3/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Rash maculo-papular	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	43.6% 17/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	23.5% 4/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Rash erythematous	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Rash generalised	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Back pain	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	43.3% 13/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.8% 5/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	19.2% 5/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Pain in extremity	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.6% 3/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.8% 5/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Arthralgia	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	26.9% 7/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Muscle spasms	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.1% 4/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Neck pain	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.3% 4/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	19.2% 5/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Myalgia	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.0% 3/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Limb discomfort	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Urinary tract infection	12.9% 4/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.0% 3/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	18.2% 6/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	27.3% 6/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.4% 6/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	30.8% 8/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Upper respiratory tract infection	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	16.7% 5/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Cellulitis	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Nasopharyngitis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Oral herpes	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.1% 4/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Sinusitis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Respiratory tract infection	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Oral candidiasis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Catheter site infection	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Oropharyngeal candidiasis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	23.3% 7/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	30.3% 10/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	18.2% 4/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	17.9% 7/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	17.6% 3/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.4% 4/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Cough	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	16.7% 5/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.1% 4/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	18.2% 4/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	23.1% 9/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	35.3% 6/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	30.8% 8/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.0% 3/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.3% 4/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	34.6% 9/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Dysphonia	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.6% 3/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Nasal dryness	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.6% 3/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.0% 3/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Blood creatinine increased	29.0% 9/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.3% 4/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.4% 6/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	23.5% 4/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	19.2% 5/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Weight decreased	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.0% 3/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.2% 5/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.4% 6/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	17.6% 3/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	26.9% 7/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Blood urea increased	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Alanine aminotransferase increased	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Aspartate aminotransferase increased	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.0% 3/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Gamma-glutamyltransferase increased	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Platelet count decreased	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Blood albumin decreased	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Blood triglycerides increased	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Blood urea decreased	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.0% 3/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Blood and lymphatic system disorders Anaemia	19.4% 6/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	16.7% 5/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	30.3% 10/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.6% 3/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.8% 5/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	42.3% 11/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Blood and lymphatic system disorders Lymphopenia	16.1% 5/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.3% 4/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Blood and lymphatic system disorders Thrombocytopenia	16.1% 5/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Psychiatric disorders Confusional state	16.1% 5/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.3% 4/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Psychiatric disorders Insomnia	9.7% 3/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 3/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	13.6% 3/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	17.6% 3/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	19.2% 5/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Psychiatric disorders Anxiety	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.1% 4/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	17.6% 3/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Psychiatric disorders Depression	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	23.5% 4/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Psychiatric disorders Agitation	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Renal and urinary disorders Haematuria	3.2% 1/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.0% 3/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.4% 4/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Renal and urinary disorders Dysuria	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Renal and urinary disorders Proteinuria	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Vascular disorders Hypotension	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	16.7% 5/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Vascular disorders Orthostatic hypotension	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Vascular disorders Hypertension	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.0% 1/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Vascular disorders Deep vein thrombosis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Cardiac disorders Tachycardia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	4.5% 1/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Cardiac disorders Palpitations	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Cardiac disorders Pericardial effusion	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	9.1% 2/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Cardiac disorders Ventricular extrasystoles	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.7% 2/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Injury, poisoning and procedural complications Contusion	6.5% 2/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	6.1% 2/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Aphthous ulcer	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Dysphagia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Glossodynia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Hiatus hernia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Lip swelling	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Oesophagitis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Coeliac disease	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Haematemesis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Oesophageal stenosis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Oesophageal ulcer	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Gastrointestinal disorders Rectal obstruction	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.3% 1/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	24.2% 8/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	22.7% 5/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.3% 4/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	19.2% 5/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.4% 4/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Malaise	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Pain	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
General disorders Early satiety	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Paraesthesia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Memory impairment	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Disturbance in attention	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Nervous system disorders Sciatica	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Osteitis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	10.3% 4/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Blister	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Conjunctivitis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Herpes zoster	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Pneumonia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Infections and infestations Clostridium difficile infection	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	12.8% 5/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.4% 4/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Nasal inflammation	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Pharyngeal inflammation	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Lymphocyte count decreased	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	15.4% 4/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Blood alkaline phosphatase increased	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations Blood potassium increased	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Investigations White blood cell count decreased	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Blood and lymphatic system disorders Coagulopathy	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Renal and urinary disorders Acute kidney injury	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.5% 3/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Renal and urinary disorders Pollakiuria	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 3/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Renal and urinary disorders Azotaemia	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Vascular disorders Flushing	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Vascular disorders Phlebitis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Vascular disorders Lymphoedema	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Eye disorders Vision blurred	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Eye disorders Blindness transient	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Ear and labyrinth disorders Tinnitus	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	11.8% 2/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	3.8% 1/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Ear and labyrinth disorders Hypoacusis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.1% 2/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Product Issues Device breakage	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	5.9% 1/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)
Psychiatric disorders Mental status changes	0.00% 0/31 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/30 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/33 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/22 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	2.6% 1/39 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	0.00% 0/17 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)	7.7% 2/26 • All cause-mortality were collected throughout the study; SAEs and Other (non-serious) were collected from the first dose of study drug plus 30 days after last dose of study drug (Up to approximately 244 weeks)

Additional Information

Medical Director

Takeda

Phone: +1-866-835-2233

Email: GlobalOncologyMedinfo@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
• Publication restrictions are in place

Restriction type: OTHER