Trial Outcomes & Findings for A Study to Evaluate the Safety, Tolerability, and Activity of TAK-931 in Participants With Metastatic Pancreatic Cancer, Metastatic Colorectal Cancer, and Other Advanced Solid Tumors (NCT NCT03261947)

NCT ID: NCT03261947

Last Updated: 2021-09-20

Results Overview

DLT:Any following event related to TAK-931 assessed by Common Terminology Criteria for Adverse Events(CTCAE) version4.03;Non-febrile Grade 4 neutropenia; febrile neutropenia: Grade \>=3 neutropenia; Grade4 thrombocytopenia; Grade \>=3 thrombocytopenia of any duration accompanied by Grade 2 bleeding or requiring transfusion; delay in initiation of Cycle 2 by \>14 days due to lack of adequate recovery of treatment-related hematological or nonhematologic toxicities; Grade 2 ejection fraction decreased by echocardiogram(ECHO) or multiple gated acquisition(MUGA) scan; Grade 4 laboratory abnormalities; other Grade 2 nonhematologic toxicities considered by investigator to be related to study drug and dose-limiting; Participants receiving \<50% of doses (\<7 doses) of planned TAK-931 dosing in Cycle 1 due to study drug-related adverse events(AEs); Grade \>=3 nonhematologic toxicity with few exceptions: Grade 3 arthralgia/myalgia, fatigue, laboratory abnormalities, nausea and/or emesis or diarrhea.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

101 participants

Primary outcome timeframe

Cycle 1 (each cycle = 21 days)

Results posted on

2021-09-20

Participant Flow

Participants took part in the study at 12 investigative sites in Japan and the United States from 25 October 2017 to 24 August 2020.

The study had two parts, Part 1 (Safety Cohort) enrolled western participants with locally advanced/metastatic solid tumors to receive TAK-931 and assessed safety, tolerability and pharmacokinetics. In Part 2, participants were enrolled into Tumor (Disease)-Specific Cohorts based on tumor criteria: pancreatic cancer, metastatic colorectal cancer (CRC), squamous esophageal cancer (sqEC), squamous non-small-cell lung cancer (sqNSCLC) to receive TAK-931 and were assessed for antitumor activity.

Participant milestones

Participant milestones
Measure	Western Safety Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Pancreatic Cancer Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	Metastatic CRC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Overall Study STARTED	12	15	35	21	18
Overall Study COMPLETED	0	2	5	0	1
Overall Study NOT COMPLETED	12	13	30	21	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Western Safety Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Pancreatic Cancer Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	Metastatic CRC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Overall Study Death	10	13	17	12	8
Overall Study Lost to Follow-up	0	0	2	1	0
Overall Study Withdrawal by Subject	0	0	3	0	1
Overall Study Site Terminated by Sponsor	0	0	4	7	5
Overall Study Reason not Specified	2	0	4	1	3

Baseline Characteristics

Number analyzed is the number of participants with data available for height at the Baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Western Safety Cohort n=12 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Pancreatic Cancer Cohort n=15 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	Metastatic CRC Cohort n=35 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=21 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort n=18 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	Total n=101 Participants Total of all reporting groups
Age, Continuous	59.3 years STANDARD_DEVIATION 7.16 • n=12 Participants	63.1 years STANDARD_DEVIATION 12.27 • n=15 Participants	58.3 years STANDARD_DEVIATION 11.93 • n=35 Participants	64.2 years STANDARD_DEVIATION 7.71 • n=21 Participants	64.4 years STANDARD_DEVIATION 7.74 • n=18 Participants	61.5 years STANDARD_DEVIATION 10.23 • n=101 Participants
Sex: Female, Male Female	5 Participants n=12 Participants	5 Participants n=15 Participants	19 Participants n=35 Participants	4 Participants n=21 Participants	7 Participants n=18 Participants	40 Participants n=101 Participants
Sex: Female, Male Male	7 Participants n=12 Participants	10 Participants n=15 Participants	16 Participants n=35 Participants	17 Participants n=21 Participants	11 Participants n=18 Participants	61 Participants n=101 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=12 Participants	1 Participants n=15 Participants	1 Participants n=35 Participants	0 Participants n=21 Participants	0 Participants n=18 Participants	2 Participants n=101 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=12 Participants	12 Participants n=15 Participants	34 Participants n=35 Participants	21 Participants n=21 Participants	18 Participants n=18 Participants	96 Participants n=101 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=12 Participants	2 Participants n=15 Participants	0 Participants n=35 Participants	0 Participants n=21 Participants	0 Participants n=18 Participants	3 Participants n=101 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=12 Participants	0 Participants n=15 Participants	0 Participants n=35 Participants	0 Participants n=21 Participants	0 Participants n=18 Participants	0 Participants n=101 Participants
Race (NIH/OMB) Asian	0 Participants n=12 Participants	3 Participants n=15 Participants	8 Participants n=35 Participants	16 Participants n=21 Participants	2 Participants n=18 Participants	29 Participants n=101 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=12 Participants	0 Participants n=15 Participants	0 Participants n=35 Participants	0 Participants n=21 Participants	0 Participants n=18 Participants	0 Participants n=101 Participants
Race (NIH/OMB) Black or African American	3 Participants n=12 Participants	0 Participants n=15 Participants	3 Participants n=35 Participants	1 Participants n=21 Participants	1 Participants n=18 Participants	8 Participants n=101 Participants
Race (NIH/OMB) White	9 Participants n=12 Participants	12 Participants n=15 Participants	24 Participants n=35 Participants	4 Participants n=21 Participants	15 Participants n=18 Participants	64 Participants n=101 Participants
Race (NIH/OMB) More than one race	0 Participants n=12 Participants	0 Participants n=15 Participants	0 Participants n=35 Participants	0 Participants n=21 Participants	0 Participants n=18 Participants	0 Participants n=101 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=12 Participants	0 Participants n=15 Participants	0 Participants n=35 Participants	0 Participants n=21 Participants	0 Participants n=18 Participants	0 Participants n=101 Participants
Region of Enrollment Japan	0 Participants n=12 Participants	3 Participants n=15 Participants	8 Participants n=35 Participants	16 Participants n=21 Participants	2 Participants n=18 Participants	29 Participants n=101 Participants
Region of Enrollment United States	12 Participants n=12 Participants	12 Participants n=15 Participants	27 Participants n=35 Participants	5 Participants n=21 Participants	16 Participants n=18 Participants	72 Participants n=101 Participants
Height	172.47 cm STANDARD_DEVIATION 13.371 • n=12 Participants • Number analyzed is the number of participants with data available for height at the Baseline.	170.61 cm STANDARD_DEVIATION 11.596 • n=15 Participants • Number analyzed is the number of participants with data available for height at the Baseline.	168.64 cm STANDARD_DEVIATION 10.203 • n=34 Participants • Number analyzed is the number of participants with data available for height at the Baseline.	167.11 cm STANDARD_DEVIATION 7.975 • n=20 Participants • Number analyzed is the number of participants with data available for height at the Baseline.	172.26 cm STANDARD_DEVIATION 10.693 • n=18 Participants • Number analyzed is the number of participants with data available for height at the Baseline.	169.75 cm STANDARD_DEVIATION 10.513 • n=99 Participants • Number analyzed is the number of participants with data available for height at the Baseline.
Weight	79.33 kg STANDARD_DEVIATION 16.052 • n=12 Participants • Number analyzed is the number of participants with data available for weight at the Baseline.	73.22 kg STANDARD_DEVIATION 22.763 • n=15 Participants • Number analyzed is the number of participants with data available for weight at the Baseline.	79.90 kg STANDARD_DEVIATION 17.457 • n=35 Participants • Number analyzed is the number of participants with data available for weight at the Baseline.	57.07 kg STANDARD_DEVIATION 10.358 • n=20 Participants • Number analyzed is the number of participants with data available for weight at the Baseline.	77.70 kg STANDARD_DEVIATION 18.770 • n=18 Participants • Number analyzed is the number of participants with data available for weight at the Baseline.	73.87 kg STANDARD_DEVIATION 19.076 • n=100 Participants • Number analyzed is the number of participants with data available for weight at the Baseline.
Substance Use Tobacco	0 Participants Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	0 Participants Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	0 Participants Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	12 Participants n=20 Participants • Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	3 Participants n=18 Participants • Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	15 Participants n=38 Participants • Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.
Substance Use Cigarette	0 Participants Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	0 Participants Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	0 Participants Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	6 Participants n=20 Participants • Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	15 Participants n=18 Participants • Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	21 Participants n=38 Participants • Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.
Substance Use Cigar	0 Participants Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	0 Participants Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	0 Participants Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	1 Participants n=20 Participants • Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	0 Participants n=18 Participants • Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	1 Participants n=38 Participants • Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.
Substance Use Pipe	0 Participants Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	0 Participants Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	0 Participants Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	1 Participants n=20 Participants • Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	0 Participants n=18 Participants • Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.	1 Participants n=38 Participants • Data for substance use was collected only for sqEC and sqNSCLC cohorts. Number analyzed is the number of participants with data available for substance use at Baseline.
Smoking Classification Never Smoked	12 Participants n=12 Participants	15 Participants n=15 Participants	35 Participants n=35 Participants	2 Participants n=21 Participants	1 Participants n=18 Participants	65 Participants n=101 Participants
Smoking Classification Current Smoker	0 Participants n=12 Participants	0 Participants n=15 Participants	0 Participants n=35 Participants	3 Participants n=21 Participants	7 Participants n=18 Participants	10 Participants n=101 Participants
Smoking Classification Former Smoker	0 Participants n=12 Participants	0 Participants n=15 Participants	0 Participants n=35 Participants	16 Participants n=21 Participants	10 Participants n=18 Participants	26 Participants n=101 Participants

PRIMARY outcome

Timeframe: Cycle 1 (each cycle = 21 days)

Population: DLT-evaluable Analysis Set included all participants in the Western Safety Cohort who received at least 1 of their planned TAK-931 doses during their first cycle of treatment (unless interrupted by related AEs) and who had sufficient follow-up data to allow the investigators and sponsor to determine whether a DLT occurred. As pre-specified in the protocol, DLTs were collected only from participants in the Western Safety Cohort who were evaluable in DLT-evaluable Analysis Set.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=2 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort	50 percentage of participants	—	—	—	—

PRIMARY outcome

Timeframe: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)

Population: Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure reports data only in the participants with locally advanced or metastatic solid tumors in the Western Safety Cohort.

An AE was 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 TEAE was defined as an adverse event with an onset that occurred after receiving study drug. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=12 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort TEAEs	100 percentage of participants	—	—	—	—
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort SAEs	58.3 percentage of participants	—	—	—	—
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort TEAEs Leading to Dose Modifications	33.3 percentage of participants	—	—	—	—
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort TEAEs Leading to Treatment Discontinuation	8.3 percentage of participants	—	—	—	—

PRIMARY outcome

Timeframe: From first dose up to end of treatment (Up to approximately 14 months)

Population: Response-evaluable Analysis Set included all participants who received at least 1 dose of study drug, had measurable disease at Baseline, and had at least 1 post-baseline response assessment. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.

DCR was defined as percentage of participants documented to have unconfirmed CR, PR, or SD for at least 6 weeks from treatment initiation according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as the best response. CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=13 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=31 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=19 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort n=17 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Disease Control Rate (DCR) in Tumor-Specific Cohorts	46.2 percentage of participants Interval 26.4 to 66.9	51.6 percentage of participants Interval 38.7 to 64.3	52.6 percentage of participants Interval 35.8 to 69.0	58.8 percentage of participants Interval 40.6 to 75.4	—

SECONDARY outcome

Timeframe: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose

Population: Pharmacokinetic (PK) Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=12 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=15 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=34 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Cmax: Maximum Observed Plasma Concentration for TAK-931 Cycle 1 Day 1	173.61 ng/mL Standard Deviation 59.677	204.69 ng/mL Standard Deviation 90.527	185.46 ng/mL Standard Deviation 61.158	—	—
Cmax: Maximum Observed Plasma Concentration for TAK-931 Cycle 1 Day 8	196.17 ng/mL Standard Deviation 73.702	180.55 ng/mL Standard Deviation 75.036	216.18 ng/mL Standard Deviation 121.488	—	—

SECONDARY outcome

Timeframe: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose

Population: PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Number analyzed is the number of participants with data available for analysis at the given timepoint.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=12 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=15 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=34 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 Cycle 1 Day 1	1.57 hour Interval 0.8 to 2.2	2.00 hour Interval 0.5 to 6.3	1.85 hour Interval 0.9 to 6.0	—	—
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 Cycle 1 Day 8	1.59 hour Interval 1.0 to 4.0	2.00 hour Interval 1.0 to 4.3	1.97 hour Interval 1.0 to 4.0	—	—

SECONDARY outcome

Timeframe: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=12 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=15 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=34 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931 Cycle 1 Day 1	1190.22 h*ng/mL Standard Deviation 540.877	1166.40 h*ng/mL Standard Deviation 362.856	1302.40 h*ng/mL Standard Deviation 391.035	—	—
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931 Cycle 1 Day 8	1475.88 h*ng/mL Standard Deviation 749.707	1290.72 h*ng/mL Standard Deviation 615.542	1542.82 h*ng/mL Standard Deviation 507.733	—	—

SECONDARY outcome

Timeframe: Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=12 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=15 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=34 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 Cycle 1 Day 1	1165.52 h*ng/mL Standard Deviation 552.287	1114.23 h*ng/mL Standard Deviation 388.844	1311.41 h*ng/mL Standard Deviation 388.557	—	—
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 Cycle 1 Day 8	1426.70 h*ng/mL Standard Deviation 774.257	1289.33 h*ng/mL Standard Deviation 616.737	1551.57 h*ng/mL Standard Deviation 497.856	—	—

SECONDARY outcome

Timeframe: Cycle 1 (each cycle = 21 days) Day 1 pre-dose and at multiple timepoints (up to 8 hours urine sampling) post-dose

Population: PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for urine PK sampling was collected only for participants in Western Safety Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.

CLr is a measure of apparent clearance of the drug from the plasma, renal clearance is a measure of drug excreted through kidneys/urine per unit time.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=4 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
CLr: Renal Clearance of TAK-931	2.16 L/h Standard Deviation 1.913	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose

Population: PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=11 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=10 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=11 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
t1/2z: Terminal Disposition Phase Half-life for TAK-931	5.95 hour Interval 4.3 to 6.7	5.53 hour Interval 3.7 to 8.0	6.18 hour Interval 4.8 to 8.4	—	—

SECONDARY outcome

Timeframe: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose

Population: PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.

CL/F was defined as apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=11 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=10 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=11 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
CLss/F: Steady-state Apparent Oral Clearance for TAK-931	39.71 L/h Standard Deviation 14.135	45.58 L/h Standard Deviation 18.877	35.57 L/h Standard Deviation 10.778	—	—

SECONDARY outcome

Timeframe: Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose

Population: PK Analysis Set included all participants for whom there was sufficient dosing and TAK-931 concentration-time data to reliably estimate the PK parameters. As prespecified in the protocol, data for intensive PK sampling was collected only for participants in Western Safety Cohort, Pancreatic Cancer Cohort, and Metastatic CRC Cohort. Overall number of participants analyzed are the number of participants with data available for analyses.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=11 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=10 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=11 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931	1.27 ratio Standard Deviation 0.317	1.10 ratio Standard Deviation 0.299	1.12 ratio Standard Deviation 0.203	—	—

SECONDARY outcome

Timeframe: From first dose up to end of treatment (Up to approximately 14 months)

Overall response rate was defined as percentage of participants documented to have unconfirmed CR or PR according to RECIST v1.1 as the best response. CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=12 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=13 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=31 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort n=19 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort n=17 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Overall Response Rate (CR and PR)	8.3 percentage of participants Interval 0.9 to 28.7	0 percentage of participants Interval 0.0 to 16.2	0 percentage of participants Interval 0.0 to 7.2	5.3 percentage of participants Interval 0.6 to 19.0	0 percentage of participants Interval 0.0 to 12.7

SECONDARY outcome

Timeframe: From first documented response until disease progression or end of treatment, whichever occurs first (Up to 14 months)

Population: Response-evaluable Analysis Set included all participants who received at least 1 dose of study drug, had measurable disease at Baseline, and had at least 1 post-baseline response assessment. Only responders were to be analyzed for this outcome measure.

DOR was defined as the time from the date of first documentation of a CR or PR to the date of first documentation of tumor progression. Per RECIST V1.1, CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=1 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort n=1 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Duration of Response (DOR)	NA months Data for median; upper and lower limits of confidence interval (CI) were not available as all responders were censored.	—	—	NA months Data for median; upper and lower limits of CI were not available as all responders were censored.	—

SECONDARY outcome

Timeframe: From date of randomization until disease progression or death, whichever occurs first (Up to approximately 34 months)

Population: Safety Analysis Set included all participants who received any amount of study drug.

PFS was defined as the time from the date of first dose to the date of first documentation of PD (including clinical progression or clinical deterioration) or death due to any cause, whichever occurs first. Per RECIST V1.1, PD was defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=12 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=15 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=35 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort n=21 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort n=18 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Progression Free Survival (PFS)	2.05 months Interval 1.31 to 5.09	1.31 months Interval 0.99 to 2.76	1.45 months Interval 1.35 to 2.56	3.02 months Interval 1.25 to 3.58	2.12 months Interval 1.28 to 3.25

SECONDARY outcome

Timeframe: Up to approximately 43 months

Population: Safety Analysis Set included all participants who received any amount of study drug. Participants without documentation of death at the time of analysis were censored at the date last known to be alive. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.

OS was defined as the time from the date of first dose of study drug to death due to any cause.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=15 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=35 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=21 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort n=18 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Overall Survival (OS) in the Tumor-Specific Cohorts	4.67 months Interval 1.77 to 7.06	7.72 months Interval 5.68 to 11.96	8.61 months Interval 3.94 to 42.71	NA months The median, upper and lower limits of 95% confidence interval were not evaluable due to fewer number of participants with events.	—

SECONDARY outcome

Timeframe: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)

Population: Safety Analysis Set included all participants who received any amount of study drug. As pre-specified in the protocol, this outcome measure evaluated and reported data for participants only in the Tumor-Specific Cohorts.

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurred after receiving study drug. TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4:Life-threatening consequences, urgent intervention indicated; Grade 5:Death related to AE. An SAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=15 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=35 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=21 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort n=18 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts Grade >=3 TEAEs	73.3 percentage of participants	54.3 percentage of participants	57.1 percentage of participants	44.4 percentage of participants	—
Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts SAEs	40.0 percentage of participants	22.9 percentage of participants	23.8 percentage of participants	16.7 percentage of participants	—
Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts TEAEs Leading to Dose Modifications	53.3 percentage of participants	48.6 percentage of participants	52.4 percentage of participants	38.9 percentage of participants	—
Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts TEAEs Leading to Treatment Discontinuation	13.3 percentage of participants	8.6 percentage of participants	9.5 percentage of participants	0 percentage of participants	—

SECONDARY outcome

Timeframe: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)

Clinical laboratory tests included hematology, clinical chemistry and urinalysis. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=15 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=35 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=21 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort n=18 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Neutrophil Count Decreased	26.7 percentage of participants	17.1 percentage of participants	38.1 percentage of participants	27.8 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts White Blood Cell Count Decreased	20.0 percentage of participants	8.6 percentage of participants	42.9 percentage of participants	5.6 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Lymphocyte Count Decreased	13.3 percentage of participants	0 percentage of participants	0 percentage of participants	5.6 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Aspartate Aminotransferase Increased	6.7 percentage of participants	2.9 percentage of participants	0 percentage of participants	5.6 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Alanine Aminotransferase Increased	6.7 percentage of participants	0 percentage of participants	0 percentage of participants	5.6 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Blood Bilirubin Increased	0 percentage of participants	2.9 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Hepatic Enzyme Increased	6.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Blood Creatinine Increased	20.0 percentage of participants	0 percentage of participants	4.8 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Blood Creatinine Decreased	6.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Blood Urea Increased	6.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Blood Chloride Decreased	6.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Blood Sodium Decreased	0 percentage of participants	2.9 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Platelet Count Decreased	0 percentage of participants	5.7 percentage of participants	4.8 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Blood Alkaline Phosphatase Increased	6.7 percentage of participants	5.7 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Blood Uric Acid Increased	6.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Blood Glucose Increased	6.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Blood Albumin Decreased	6.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Protein Total Decreased	6.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Haematocrit Decreased	6.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts Red Blood Cell Count Decreased	6.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—

SECONDARY outcome

Timeframe: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months)

Vital signs included assessments of systolic and diastolic blood pressure (BP), heart rate (HR), and body temperature. The investigator determined if the results were clinically significant. Only those categories were reported which are clinically significant at post Baseline.

Outcome measures

Outcome measures
Measure	Western Safety Cohort n=15 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Metastatic CRC Cohort n=35 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=21 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort n=18 Participants TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.	sqNSCLC Cohort TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts Orthostatic Hypotension	0 percentage of participants	2.9 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts Tachycardia	0 percentage of participants	5.7 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts Bradycardia	0 percentage of participants	2.9 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts Atrial Fibrillation	0 percentage of participants	2.9 percentage of participants	0 percentage of participants	0 percentage of participants	—
Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts Increase in HR	0 percentage of participants	2.9 percentage of participants	0 percentage of participants	0 percentage of participants	—

Adverse Events

Western Safety Cohort

Serious events: 7 serious events

Other events: 5 other events

Deaths: 10 deaths

Pancreatic Cancer Cohort

Serious events: 6 serious events

Other events: 8 other events

Deaths: 13 deaths

Metastatic CRC Cohort

Serious events: 8 serious events

Other events: 27 other events

Deaths: 17 deaths

sqEC Cohort

Serious events: 5 serious events

Other events: 14 other events

Deaths: 12 deaths

sqNSCLC Cohort

Serious events: 3 serious events

Other events: 14 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	Western Safety Cohort n=12 participants at risk TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Pancreatic Cancer Cohort n=15 participants at risk TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	Metastatic CRC Cohort n=35 participants at risk TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=21 participants at risk TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort n=18 participants at risk TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Gastrointestinal disorders Abdominal pain	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	4.8% 1/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Nausea	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	13.3% 2/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Vomiting	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Duodenal ulcer perforation	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Constipation	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Large intestine perforation	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	16.7% 2/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	4.8% 1/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	4.8% 1/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	4.8% 1/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	4.8% 1/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Pulmonary alveolar haemorrhage	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Infections and infestations Abdominal infection	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Infections and infestations Pneumonia	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Infections and infestations Sepsis	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Infections and infestations Pyelonephritis	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Metabolism and nutrition disorders Dehydration	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	4.8% 1/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Metabolism and nutrition disorders Hyponatraemia	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	4.8% 1/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Musculoskeletal and connective tissue disorders Pain in extremity	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Nervous system disorders Migraine	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Nervous system disorders Dizziness	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	4.8% 1/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
General disorders Disease progression	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Hepatobiliary disorders Bile duct stenosis	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Neutrophil count decreased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Psychiatric disorders Mental status changes	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	2.9% 1/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Renal and urinary disorders Acute kidney injury	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.

Other adverse events

Other adverse events
Measure	Western Safety Cohort n=12 participants at risk TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, once daily (QD) for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 20 cycles. Participants with locally advanced or metastatic solid tumors with no standard therapeutic alternative in the United States were included in this cohort.	Pancreatic Cancer Cohort n=15 participants at risk TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 4 cycles. Participants with metastatic pancreatic cancer who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	Metastatic CRC Cohort n=35 participants at risk TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 12 cycles. Participants with metastatic CRC who had progressed after at least 2 lines of previous standard chemotherapy were included in this cohort.	sqEC Cohort n=21 participants at risk TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 8 cycles. Participants with metastatic sqEC who had progressed after at least 1 line of standard chemotherapy were included in this cohort.	sqNSCLC Cohort n=18 participants at risk TAK-931 50 mg (2x25 mg or 5x10 mg), capsules, orally, QD for 14 days, followed by a 7-day washout period (14 days on and 7 days off study drug), in 21-day cycles until disease progression or unacceptable treatment-related toxicity up to 18 cycles. Participants with metastatic sqNSCLC who had progressed after at least 2 lines of standard treatment were included in this cohort.
Gastrointestinal disorders Nausea	25.0% 3/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	33.3% 5/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	45.7% 16/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	33.3% 7/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	38.9% 7/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Vomiting	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	20.0% 3/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	40.0% 14/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	9.5% 2/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	38.9% 7/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Constipation	16.7% 2/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	13.3% 2/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	17.1% 6/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	22.2% 4/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Abdominal pain	25.0% 3/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	17.1% 6/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.1% 2/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Diarrhoea	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	14.3% 5/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.1% 2/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Dyspepsia	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.4% 4/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.1% 2/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Proctalgia	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Abdominal distension	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Ascites	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Faeces discoloured	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Flatulence	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Gingival bleeding	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Rectal discharge	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Rectal haemorrhage	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Retching	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Gastrointestinal disorders Stomatitis	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Neutrophil count decreased	25.0% 3/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	13.3% 2/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.4% 4/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	28.6% 6/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	27.8% 5/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations White blood cell count decreased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	8.6% 3/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	33.3% 7/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Ejection fraction decreased	16.7% 2/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.1% 2/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Weight decreased	16.7% 2/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	9.5% 2/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Blood alkaline phosphatase increased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Alanine aminotransferase increased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Aspartate aminotransferase increased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Lymphocyte count decreased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Platelet count decreased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Blood albumin decreased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Blood chloride decreased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Blood creatinine decreased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Blood creatinine increased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Blood glucose increased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Blood urea increased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Blood uric acid increased	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Haematocrit decreased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Hepatic enzyme increased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Protein total decreased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Red blood cell count decreased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Investigations Weight increased	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Metabolism and nutrition disorders Decreased appetite	33.3% 4/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	13.3% 2/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	17.1% 6/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	28.6% 6/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	27.8% 5/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Metabolism and nutrition disorders Dehydration	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	8.6% 3/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.1% 2/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	8.6% 3/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Metabolism and nutrition disorders Hyperglycaemia	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Metabolism and nutrition disorders Iron deficiency	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
General disorders Fatigue	33.3% 4/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	33.3% 5/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	8.6% 3/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	9.5% 2/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.1% 2/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
General disorders Malaise	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	8.6% 3/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	9.5% 2/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
General disorders Early satiety	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
General disorders Oedema peripheral	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
General disorders Asthenia	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
General disorders Chest pain	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
General disorders Chills	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
General disorders Pain	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
General disorders Pyrexia	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Skin and subcutaneous tissue disorders Alopecia	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	8.6% 3/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	14.3% 3/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	27.8% 5/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Skin and subcutaneous tissue disorders Pruritus	16.7% 2/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.4% 4/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Skin and subcutaneous tissue disorders Rash	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	13.3% 2/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	8.6% 3/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Skin and subcutaneous tissue disorders Dry skin	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.1% 2/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Skin and subcutaneous tissue disorders Rash maculo-papular	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Skin and subcutaneous tissue disorders Dermatitis bullous	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Skin and subcutaneous tissue disorders Photosensitivity reaction	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Nervous system disorders Dizziness	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	13.3% 2/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	8.6% 3/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Nervous system disorders Dysgeusia	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	8.6% 3/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.1% 2/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Nervous system disorders Headache	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	8.6% 3/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.1% 2/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Nervous system disorders Peripheral sensory neuropathy	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Nervous system disorders Tremor	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Nervous system disorders Neuropathy peripheral	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Blood and lymphatic system disorders Anaemia	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	13.3% 2/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.4% 4/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	9.5% 2/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	16.7% 3/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Blood and lymphatic system disorders Neutropenia	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	9.5% 2/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.1% 2/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Blood and lymphatic system disorders Increased tendency to bruise	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.4% 4/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Musculoskeletal and connective tissue disorders Myalgia	25.0% 3/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 2/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.4% 4/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	13.3% 2/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	22.2% 4/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Infections and infestations Upper respiratory tract infection	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	16.7% 3/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Infections and infestations Pneumonia	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Infections and infestations Candida infection	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Infections and infestations Cellulitis	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Infections and infestations Kidney infection	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Infections and infestations Localised infection	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Infections and infestations Skin infection	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Psychiatric disorders Insomnia	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.6% 1/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Psychiatric disorders Depression	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	9.5% 2/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Injury, poisoning and procedural complications Contusion	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Injury, poisoning and procedural complications Foot fracture	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Injury, poisoning and procedural complications Wound	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Cardiac disorders Tachycardia	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	5.7% 2/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Eye disorders Vision blurred	8.3% 1/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Eye disorders Vitreous floaters	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Renal and urinary disorders Dysuria	16.7% 2/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Vascular disorders Hot flush	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	11.1% 2/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Ear and labyrinth disorders Ear pain	0.00% 0/12 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	6.7% 1/15 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/35 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/21 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/18 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.
Reproductive system and breast disorders Vulvovaginal pruritus	0.00% 0/5 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	20.0% 1/5 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/19 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/4 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.	0.00% 0/4 • All-Cause Mortality: Up to approximately 43 months; Serious and Other Adverse Events: From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. A total of 67 deaths occurred in this study. Since all the information for death data could not be collected, not all deaths could be reported in all-cause mortality.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Publication restrictions are in place

Restriction type: OTHER