Trial Outcomes & Findings for A Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100) (NCT NCT02493751)

NCT ID: NCT02493751

Last Updated: 2022-02-18

Results Overview

DLT: greater than or equal to (\>=) Grade 3 hematologic/non-hematologic toxicity, Grade 3-4 liver-related laboratory test elevation (alanine aminotransferase, aspartate aminotransferase) with Grade 2 elevation of total bilirubin, non-hematologic Grade 3 laboratory abnormality (required medical intervention to treat participant/led to hospitalization), inability to complete \>=75% of first 2 cycles doses of axitinib (from Cycle 1 Day 1 after completion of lead-in period) or 2 infusions of avelumab within DLT observation period due to investigational product related toxicity.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 55 participants
• Primary outcome timeframe: DLT observation period (from the beginning of Cycle 1 up to the end of Cycle 2 [28 days])
• Results posted on: 2022-02-18

Participant Flow

In this study, a lead-in period was conducted (only axitinib administered) in few participants prior to the administration of combination treatment (axitinib+avelumab) in treatment period. After 5 years from study initiation, the study was closed by Sponsor due to an internal decision (ie, end of study). No safety concerns were related to the study closure. Data reported based on last participant last visit (LPLV) date (04 March 2021).

Participant milestones

Measure	Axitinib + Avelumab With Lead-in Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Overall Study STARTED	16	39
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	16	39

Reasons for withdrawal

Measure	Axitinib + Avelumab With Lead-in Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Overall Study Withdrawal by Subject	2	8
Overall Study Death	6	13
Overall Study Lost to Follow-up	2	3
Overall Study Study closed by Sponsor due to an internal decision with no safety concerns related.	6	15

Baseline Characteristics

A Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100)

Baseline characteristics by cohort

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).	Total n=55 Participants Total of all reporting groups
Age, Continuous	60.0 years STANDARD_DEVIATION 8.45 • n=93 Participants	60.5 years STANDARD_DEVIATION 8.89 • n=4 Participants	60.3 years STANDARD_DEVIATION 8.69 • n=27 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	11 Participants n=4 Participants	13 Participants n=27 Participants
Sex: Female, Male Male	14 Participants n=93 Participants	28 Participants n=4 Participants	42 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=93 Participants	35 Participants n=4 Participants	51 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized Asian	0 Participants n=93 Participants	6 Participants n=4 Participants	6 Participants n=27 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized White	15 Participants n=93 Participants	29 Participants n=4 Participants	44 Participants n=27 Participants
Race/Ethnicity, Customized Other	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants

PRIMARY outcome

Timeframe: DLT observation period (from the beginning of Cycle 1 up to the end of Cycle 2 [28 days])

Population: DLT evaluable analysis set: First 6 enrolled participants who received at least 1 dose of avelumab and axitinib, and either experienced DLT during DLT observation period or completed it. Data for this endpoint was only planned to be collected and analyzed for "Axitinib + Avelumab with Lead-in" arm.

DLT: greater than or equal to (>=) Grade 3 hematologic/non-hematologic toxicity, Grade 3-4 liver-related laboratory test elevation (alanine aminotransferase, aspartate aminotransferase) with Grade 2 elevation of total bilirubin, non-hematologic Grade 3 laboratory abnormality (required medical intervention to treat participant/led to hospitalization), inability to complete >=75% of first 2 cycles doses of axitinib (from Cycle 1 Day 1 after completion of lead-in period) or 2 infusions of avelumab within DLT observation period due to investigational product related toxicity.

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=6 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Number of Participants With Dose Limiting Toxicities (DLTs)	1 Participants	—

SECONDARY outcome

Timeframe: Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks)

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib.

Adverse event (AE)=any untoward medical occurrence in participant who received study treatment without regard to causality. TEAE=event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or worsened relative to pretreatment state. Serious AE (SAE)=AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs were graded by worst National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 severity grade. Grade 3 event=unacceptable or intolerable event, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 event caused participant to be in imminent danger of death. Grade 5 event=death related to AE. The results reflect data available on cutoff of LPLV (04 Mar 2021).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) Participants with TEAEs	16 Participants	39 Participants
Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) Participants with Grade >=3 TEAEs	13 Participants	30 Participants
Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) Participants with SAEs	6 Participants	18 Participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks)

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib.

Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE=event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs were graded by worst NCI CTCAE v4.03 severity grade. Grade 3 events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events caused participant to be in imminent danger of death. Grade 5 events=death related to an AE. Treatment-related AEs and SAEs were determined by the investigator. The results reflect data available on cutoff of LPLV (04 Mar 2021).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Number of Participants With Treatment-related TEAEs Participants with treatment-related SAEs	3 Participants	10 Participants
Number of Participants With Treatment-related TEAEs Participants with treatment-related TEAEs	15 Participants	39 Participants
Number of Participants With Treatment-related TEAEs Participants with Grade >=3 treatment-related TEAEs	11 Participants	23 Participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks)

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib.

Laboratory abnormalities (hematology) reported included anemia, platelet count decreased, lymphocyte count decreased, and neutrophil count decreased. Grade 1=mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2=therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for <=24 hours. Grade 3=prolonged; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4=life threatening consequences; urgent intervention indicated. Grade 5=death. The results reflect data available on cutoff of LPLV (04 Mar 2021).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology Participants with Grade >=1 platelet count decreased	4 Participants	11 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology Participants with Grade >=1 anemia	8 Participants	24 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology Participants with Grade >=3 anemia	0 Participants	2 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology Participants with Grade >=3 platelet count decreased	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology Participants with Grade >=1 lymphocyte count decreased	10 Participants	16 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology Participants with Grade >=3 lymphocyte count decreased	1 Participants	3 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology Participants with Grade >=1 neutrophil count decreased	1 Participants	4 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology Participants with Grade >=3 neutrophil count decreased	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks)

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib.

Laboratory abnormalities (chemistry) reported included creatinine increased, serum amylase increased, lipase increased, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatine kinase increased, hypoglycemia, and hyperglycemia. Grade 1=mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2=therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for <=24 hours. Grade 3=prolonged; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4=life threatening consequences; urgent intervention indicated. Grade 5=death. The results reflect data available on cutoff of LPLV (04 Mar 2021).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=3 ALT increased	2 Participants	2 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=1 creatinine increased	16 Participants	37 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=3 creatinine increased	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=1 serum amylase increased	11 Participants	16 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=3 serum amylase increased	4 Participants	3 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=1 lipase increased	9 Participants	16 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=3 lipase increased	5 Participants	8 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=1 ALT increased	8 Participants	20 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=1 AST increased	10 Participants	21 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=3 AST increased	1 Participants	1 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=1 blood bilirubin increased	2 Participants	7 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=3 blood bilirubin increased	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=1 creatine kinase increased	6 Participants	15 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=3 creatine kinase increased	1 Participants	0 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=1 hypoglycemia	4 Participants	4 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=3 hypoglycemia	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=1 hyperglycemia	5 Participants	13 Participants
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Participants with Grade >=3 hyperglycemia	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib (ie, safety analysis set). Number of Participants Analyzed represents the total number of participants in the safety analysis set. Number Analyzed in each row represents the number of participants in the safety analysis set with at least 1 baseline and 1 post-baseline assessments at the visit.

Blood pressure was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of primary completion date (PCD) (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C7D1	4.8 millimeter of mercury (mm Hg) Standard Deviation 11.82	7.5 millimeter of mercury (mm Hg) Standard Deviation 12.50
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C8D1	5.7 millimeter of mercury (mm Hg) Standard Deviation 10.76	9.0 millimeter of mercury (mm Hg) Standard Deviation 10.86
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C45D1	8.1 millimeter of mercury (mm Hg) Standard Deviation 10.23	5.4 millimeter of mercury (mm Hg) Standard Deviation 13.16
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C50D1	9.0 millimeter of mercury (mm Hg) Standard Deviation 9.27	7.0 millimeter of mercury (mm Hg) Standard Deviation 11.53
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure Lead-in Day 7	5.4 millimeter of mercury (mm Hg) Standard Deviation 9.32	—
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C1D1	4.1 millimeter of mercury (mm Hg) Standard Deviation 9.36	—
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C1D8	3.2 millimeter of mercury (mm Hg) Standard Deviation 12.80	9.8 millimeter of mercury (mm Hg) Standard Deviation 11.81
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C2D1	3.4 millimeter of mercury (mm Hg) Standard Deviation 13.15	10.1 millimeter of mercury (mm Hg) Standard Deviation 10.03
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C2D8	1.8 millimeter of mercury (mm Hg) Standard Deviation 10.01	14.7 millimeter of mercury (mm Hg) Standard Deviation 5.03
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C3D1	6.1 millimeter of mercury (mm Hg) Standard Deviation 12.16	10.2 millimeter of mercury (mm Hg) Standard Deviation 11.80
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C4D1	3.6 millimeter of mercury (mm Hg) Standard Deviation 10.34	8.8 millimeter of mercury (mm Hg) Standard Deviation 9.60
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C5D1	4.8 millimeter of mercury (mm Hg) Standard Deviation 10.53	6.9 millimeter of mercury (mm Hg) Standard Deviation 11.64
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C6D1	3.0 millimeter of mercury (mm Hg) Standard Deviation 9.84	7.5 millimeter of mercury (mm Hg) Standard Deviation 11.76
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C9D1	3.9 millimeter of mercury (mm Hg) Standard Deviation 10.80	10.0 millimeter of mercury (mm Hg) Standard Deviation 13.44
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C10D1	7.3 millimeter of mercury (mm Hg) Standard Deviation 9.80	7.7 millimeter of mercury (mm Hg) Standard Deviation 8.97
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C11D1	7.4 millimeter of mercury (mm Hg) Standard Deviation 8.98	7.5 millimeter of mercury (mm Hg) Standard Deviation 11.09
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C12D1	5.3 millimeter of mercury (mm Hg) Standard Deviation 8.20	6.6 millimeter of mercury (mm Hg) Standard Deviation 12.07
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C13D1	6.0 millimeter of mercury (mm Hg) Standard Deviation 7.71	10.5 millimeter of mercury (mm Hg) Standard Deviation 11.92
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C14D1	5.4 millimeter of mercury (mm Hg) Standard Deviation 10.87	7.2 millimeter of mercury (mm Hg) Standard Deviation 14.04
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C15D1	6.9 millimeter of mercury (mm Hg) Standard Deviation 6.56	7.6 millimeter of mercury (mm Hg) Standard Deviation 12.13
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C16D1	7.5 millimeter of mercury (mm Hg) Standard Deviation 10.33	5.8 millimeter of mercury (mm Hg) Standard Deviation 13.57
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C17D1	6.2 millimeter of mercury (mm Hg) Standard Deviation 9.84	6.4 millimeter of mercury (mm Hg) Standard Deviation 13.20
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C18D1	4.3 millimeter of mercury (mm Hg) Standard Deviation 8.45	5.1 millimeter of mercury (mm Hg) Standard Deviation 12.22
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C19D1	6.3 millimeter of mercury (mm Hg) Standard Deviation 7.58	5.5 millimeter of mercury (mm Hg) Standard Deviation 10.67
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C20D1	7.9 millimeter of mercury (mm Hg) Standard Deviation 6.71	6.9 millimeter of mercury (mm Hg) Standard Deviation 11.69
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C21D1	8.9 millimeter of mercury (mm Hg) Standard Deviation 9.35	6.6 millimeter of mercury (mm Hg) Standard Deviation 10.22
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C22D1	7.2 millimeter of mercury (mm Hg) Standard Deviation 9.34	6.2 millimeter of mercury (mm Hg) Standard Deviation 11.96
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C23D1	9.2 millimeter of mercury (mm Hg) Standard Deviation 9.54	4.5 millimeter of mercury (mm Hg) Standard Deviation 11.52
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C24D1	7.3 millimeter of mercury (mm Hg) Standard Deviation 8.42	4.3 millimeter of mercury (mm Hg) Standard Deviation 12.91
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C25D1	3.1 millimeter of mercury (mm Hg) Standard Deviation 9.62	6.0 millimeter of mercury (mm Hg) Standard Deviation 13.34
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C26D1	5.6 millimeter of mercury (mm Hg) Standard Deviation 9.65	7.8 millimeter of mercury (mm Hg) Standard Deviation 12.33
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C27D1	4.5 millimeter of mercury (mm Hg) Standard Deviation 8.64	6.2 millimeter of mercury (mm Hg) Standard Deviation 13.39
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C28D1	4.9 millimeter of mercury (mm Hg) Standard Deviation 7.53	6.2 millimeter of mercury (mm Hg) Standard Deviation 13.35
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C29D1	5.4 millimeter of mercury (mm Hg) Standard Deviation 9.90	7.1 millimeter of mercury (mm Hg) Standard Deviation 11.13
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C30D1	5.6 millimeter of mercury (mm Hg) Standard Deviation 8.53	6.1 millimeter of mercury (mm Hg) Standard Deviation 13.32
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C31D1	4.8 millimeter of mercury (mm Hg) Standard Deviation 11.40	6.7 millimeter of mercury (mm Hg) Standard Deviation 10.41
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C32D1	7.1 millimeter of mercury (mm Hg) Standard Deviation 11.06	7.6 millimeter of mercury (mm Hg) Standard Deviation 13.52
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C33D1	5.5 millimeter of mercury (mm Hg) Standard Deviation 6.59	3.6 millimeter of mercury (mm Hg) Standard Deviation 13.67
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C34D1	3.5 millimeter of mercury (mm Hg) Standard Deviation 13.67	5.0 millimeter of mercury (mm Hg) Standard Deviation 15.71
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C35D1	7.2 millimeter of mercury (mm Hg) Standard Deviation 9.76	8.1 millimeter of mercury (mm Hg) Standard Deviation 12.46
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C36D1	7.5 millimeter of mercury (mm Hg) Standard Deviation 9.40	10.9 millimeter of mercury (mm Hg) Standard Deviation 11.31
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C37D1	9.9 millimeter of mercury (mm Hg) Standard Deviation 10.47	7.6 millimeter of mercury (mm Hg) Standard Deviation 13.32
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C38D1	5.0 millimeter of mercury (mm Hg) Standard Deviation 8.92	6.9 millimeter of mercury (mm Hg) Standard Deviation 12.73
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C39D1	6.6 millimeter of mercury (mm Hg) Standard Deviation 10.10	7.9 millimeter of mercury (mm Hg) Standard Deviation 14.61
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C40D1	7.8 millimeter of mercury (mm Hg) Standard Deviation 10.75	6.0 millimeter of mercury (mm Hg) Standard Deviation 13.08
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C41D1	6.6 millimeter of mercury (mm Hg) Standard Deviation 9.76	8.4 millimeter of mercury (mm Hg) Standard Deviation 11.70
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C42D1	5.9 millimeter of mercury (mm Hg) Standard Deviation 9.35	5.7 millimeter of mercury (mm Hg) Standard Deviation 13.64
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C43D1	13.0 millimeter of mercury (mm Hg) Standard Deviation 11.53	2.5 millimeter of mercury (mm Hg) Standard Deviation 7.73
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C44D1	8.3 millimeter of mercury (mm Hg) Standard Deviation 11.04	6.6 millimeter of mercury (mm Hg) Standard Deviation 10.08
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C46D1	11.1 millimeter of mercury (mm Hg) Standard Deviation 11.27	3.0 millimeter of mercury (mm Hg) Standard Deviation 14.03
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C47D1	8.4 millimeter of mercury (mm Hg) Standard Deviation 13.62	1.1 millimeter of mercury (mm Hg) Standard Deviation 12.01
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C48D1	6.3 millimeter of mercury (mm Hg) Standard Deviation 9.75	3.9 millimeter of mercury (mm Hg) Standard Deviation 13.37
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C49D1	9.4 millimeter of mercury (mm Hg) Standard Deviation 10.67	11.8 millimeter of mercury (mm Hg) Standard Deviation 11.44
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C51D1	9.3 millimeter of mercury (mm Hg) Standard Deviation 10.17	4.3 millimeter of mercury (mm Hg) Standard Deviation 10.14
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C52D1	9.3 millimeter of mercury (mm Hg) Standard Deviation 11.60	8.2 millimeter of mercury (mm Hg) Standard Deviation 11.48
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C53D1	15.4 millimeter of mercury (mm Hg) Standard Deviation 18.37	2.0 millimeter of mercury (mm Hg) Standard Deviation 14.72
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C54D1	12.5 millimeter of mercury (mm Hg) Standard Deviation 7.42	0.3 millimeter of mercury (mm Hg) Standard Deviation 12.66
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C55D1	16.0 millimeter of mercury (mm Hg) Standard Deviation 19.71	-3.0 millimeter of mercury (mm Hg) Standard Deviation NA Standard deviation was not calculated for n\<3.
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C56D1	10.0 millimeter of mercury (mm Hg) Standard Deviation 13.74	0.0 millimeter of mercury (mm Hg) Standard Deviation NA Standard deviation was not calculated for n\<3.
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C57D1	14.5 millimeter of mercury (mm Hg) Standard Deviation 12.15	—
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C58D1	16.5 millimeter of mercury (mm Hg) Standard Deviation 12.82	—
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C59D1	26.5 millimeter of mercury (mm Hg) Standard Deviation 9.19	—
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C60D1	22.5 millimeter of mercury (mm Hg) Standard Deviation 4.95	—
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C61D1	24.5 millimeter of mercury (mm Hg) Standard Deviation 4.95	—
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure C62D1	22.0 millimeter of mercury (mm Hg) Standard Deviation 1.41	—
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure End of Treatment	-1.6 millimeter of mercury (mm Hg) Standard Deviation 10.38	2.5 millimeter of mercury (mm Hg) Standard Deviation 13.05
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure Follow-up Day 30	-3.2 millimeter of mercury (mm Hg) Standard Deviation 8.41	-2.9 millimeter of mercury (mm Hg) Standard Deviation 12.51
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure Follow-up Day 60	-4.7 millimeter of mercury (mm Hg) Standard Deviation 10.26	3.8 millimeter of mercury (mm Hg) Standard Deviation 8.33
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure Follow-up Day 90	-2.0 millimeter of mercury (mm Hg) Standard Deviation 4.58	1.3 millimeter of mercury (mm Hg) Standard Deviation 6.18

SECONDARY outcome

Timeframe: Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib (ie, safety analysis set). Number of Participants Analyzed represents the total number of participants in the safety analysis set. Number Analyzed in each row represents the number of participants in the safety analysis set with at least 1 baseline and 1 post-baseline assessments at the visit.

Blood pressure was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C38D1	8.3 mm Hg Standard Deviation 11.83	4.9 mm Hg Standard Deviation 14.66
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C39D1	3.8 mm Hg Standard Deviation 13.33	4.3 mm Hg Standard Deviation 15.83
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C40D1	10.9 mm Hg Standard Deviation 14.13	3.8 mm Hg Standard Deviation 12.86
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C41D1	7.9 mm Hg Standard Deviation 16.74	3.7 mm Hg Standard Deviation 14.22
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C42D1	11.6 mm Hg Standard Deviation 15.74	0.9 mm Hg Standard Deviation 15.02
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C43D1	12.3 mm Hg Standard Deviation 13.20	-1.9 mm Hg Standard Deviation 11.49
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C44D1	9.6 mm Hg Standard Deviation 21.41	0.8 mm Hg Standard Deviation 5.70
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C45D1	9.1 mm Hg Standard Deviation 17.71	-3.5 mm Hg Standard Deviation 14.18
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C46D1	6.1 mm Hg Standard Deviation 11.28	-3.4 mm Hg Standard Deviation 10.65
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C47D1	6.6 mm Hg Standard Deviation 18.31	2.8 mm Hg Standard Deviation 13.29
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C48D1	-0.1 mm Hg Standard Deviation 15.04	-1.3 mm Hg Standard Deviation 9.50
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C49D1	5.4 mm Hg Standard Deviation 13.73	7.0 mm Hg Standard Deviation 14.11
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C50D1	9.7 mm Hg Standard Deviation 10.50	0.9 mm Hg Standard Deviation 10.06
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C51D1	13.5 mm Hg Standard Deviation 13.85	1.4 mm Hg Standard Deviation 10.01
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C52D1	4.3 mm Hg Standard Deviation 16.17	5.4 mm Hg Standard Deviation 17.74
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C53D1	17.0 mm Hg Standard Deviation 16.29	1.5 mm Hg Standard Deviation 17.94
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C54D1	10.8 mm Hg Standard Deviation 14.20	0.0 mm Hg Standard Deviation 18.36
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C55D1	15.8 mm Hg Standard Deviation 19.17	6.0 mm Hg Standard Deviation NA Standard deviation was not calculated for n\<3.
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C56D1	8.5 mm Hg Standard Deviation 11.62	3.0 mm Hg Standard Deviation NA Standard deviation was not calculated for n\<3.
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C57D1	11.5 mm Hg Standard Deviation 12.23	—
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C58D1	8.0 mm Hg Standard Deviation 17.45	—
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C59D1	21.5 mm Hg Standard Deviation 4.95	—
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C60D1	22.0 mm Hg Standard Deviation 19.80	—
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C61D1	20.0 mm Hg Standard Deviation 15.56	—
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C62D1	14.5 mm Hg Standard Deviation 13.44	—
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure End of Treatment	11.3 mm Hg Standard Deviation 25.45	3.5 mm Hg Standard Deviation 18.94
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure Follow-up Day 30	15.0 mm Hg Standard Deviation 20.65	1.7 mm Hg Standard Deviation 18.67
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure Follow-up Day 60	16.0 mm Hg Standard Deviation 9.54	15.3 mm Hg Standard Deviation 15.68
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure Follow-up Day 90	20.7 mm Hg Standard Deviation 13.32	9.3 mm Hg Standard Deviation 10.24
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure Lead-in Day 7	9.7 mm Hg Standard Deviation 13.44	—
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C1D1	11.0 mm Hg Standard Deviation 18.20	—
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C1D8	8.0 mm Hg Standard Deviation 18.94	10.3 mm Hg Standard Deviation 16.12
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C2D1	4.6 mm Hg Standard Deviation 18.49	11.2 mm Hg Standard Deviation 11.47
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C2D8	0.8 mm Hg Standard Deviation 15.63	17.7 mm Hg Standard Deviation 6.66
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C3D1	9.9 mm Hg Standard Deviation 18.96	8.7 mm Hg Standard Deviation 15.05
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C4D1	6.7 mm Hg Standard Deviation 15.61	5.8 mm Hg Standard Deviation 11.73
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C5D1	6.2 mm Hg Standard Deviation 19.45	6.7 mm Hg Standard Deviation 14.90
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C6D1	6.5 mm Hg Standard Deviation 15.05	5.2 mm Hg Standard Deviation 13.34
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C7D1	10.2 mm Hg Standard Deviation 14.46	6.1 mm Hg Standard Deviation 14.49
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C8D1	13.5 mm Hg Standard Deviation 12.07	8.0 mm Hg Standard Deviation 15.14
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C9D1	11.4 mm Hg Standard Deviation 14.24	10.2 mm Hg Standard Deviation 16.29
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C10D1	8.9 mm Hg Standard Deviation 16.83	8.4 mm Hg Standard Deviation 15.69
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C11D1	7.8 mm Hg Standard Deviation 15.36	7.2 mm Hg Standard Deviation 14.83
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C12D1	6.8 mm Hg Standard Deviation 11.27	4.1 mm Hg Standard Deviation 14.29
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C13D1	7.3 mm Hg Standard Deviation 11.17	8.6 mm Hg Standard Deviation 16.01
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C14D1	5.8 mm Hg Standard Deviation 15.49	3.9 mm Hg Standard Deviation 17.66
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C15D1	7.3 mm Hg Standard Deviation 13.89	7.3 mm Hg Standard Deviation 20.46
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C16D1	6.2 mm Hg Standard Deviation 13.46	5.5 mm Hg Standard Deviation 16.80
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C17D1	7.3 mm Hg Standard Deviation 15.55	3.5 mm Hg Standard Deviation 17.32
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C18D1	3.5 mm Hg Standard Deviation 14.67	4.2 mm Hg Standard Deviation 15.07
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C19D1	5.8 mm Hg Standard Deviation 16.04	2.6 mm Hg Standard Deviation 14.15
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C20D1	8.3 mm Hg Standard Deviation 9.67	1.1 mm Hg Standard Deviation 12.20
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C21D1	5.0 mm Hg Standard Deviation 14.14	3.1 mm Hg Standard Deviation 10.17
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C22D1	2.9 mm Hg Standard Deviation 14.53	0.2 mm Hg Standard Deviation 14.31
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C23D1	9.3 mm Hg Standard Deviation 14.19	1.5 mm Hg Standard Deviation 15.05
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C24D1	9.1 mm Hg Standard Deviation 12.55	-0.1 mm Hg Standard Deviation 16.57
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C25D1	4.0 mm Hg Standard Deviation 12.78	3.5 mm Hg Standard Deviation 15.28
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C26D1	2.8 mm Hg Standard Deviation 15.86	3.4 mm Hg Standard Deviation 15.82
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C27D1	5.4 mm Hg Standard Deviation 14.74	1.6 mm Hg Standard Deviation 16.13
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C28D1	7.8 mm Hg Standard Deviation 14.49	2.1 mm Hg Standard Deviation 16.65
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C29D1	3.3 mm Hg Standard Deviation 14.28	4.1 mm Hg Standard Deviation 11.82
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C30D1	6.4 mm Hg Standard Deviation 13.57	2.9 mm Hg Standard Deviation 15.17
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C31D1	2.7 mm Hg Standard Deviation 13.14	1.7 mm Hg Standard Deviation 10.52
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C32D1	8.6 mm Hg Standard Deviation 16.71	3.8 mm Hg Standard Deviation 14.22
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C33D1	2.9 mm Hg Standard Deviation 16.07	0.2 mm Hg Standard Deviation 15.02
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C34D1	2.8 mm Hg Standard Deviation 18.79	2.5 mm Hg Standard Deviation 15.97
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C35D1	10.3 mm Hg Standard Deviation 13.47	2.9 mm Hg Standard Deviation 12.89
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C36D1	9.0 mm Hg Standard Deviation 12.92	5.3 mm Hg Standard Deviation 19.01
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure C37D1	10.2 mm Hg Standard Deviation 11.48	2.7 mm Hg Standard Deviation 16.02

SECONDARY outcome

Timeframe: Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib (ie, safety analysis set). Number of Participants Analyzed represents the total number of participants in the safety analysis set. Number Analyzed in each row represents the number of participants in the safety analysis set with at least 1 baseline and 1 post-baseline assessments at the visit.

Pulse rate was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Change From Baseline in Vital Signs - Pulse Rate C43D1	4.5 beats per minute (bpm) Interval -16.0 to 12.0	1.0 beats per minute (bpm) Interval -19.0 to 20.0
Change From Baseline in Vital Signs - Pulse Rate C44D1	2.0 beats per minute (bpm) Interval -13.0 to 19.0	5.0 beats per minute (bpm) Interval -7.0 to 29.0
Change From Baseline in Vital Signs - Pulse Rate Lean-in Day 7	-0.5 beats per minute (bpm) Interval -16.0 to 28.0	—
Change From Baseline in Vital Signs - Pulse Rate C1D1	-1.0 beats per minute (bpm) Interval -21.0 to 19.0	—
Change From Baseline in Vital Signs - Pulse Rate C1D8	-2.0 beats per minute (bpm) Interval -20.0 to 24.0	-2.0 beats per minute (bpm) Interval -27.0 to 41.0
Change From Baseline in Vital Signs - Pulse Rate C2D1	3.0 beats per minute (bpm) Interval -20.0 to 24.0	4.0 beats per minute (bpm) Interval -30.0 to 29.0
Change From Baseline in Vital Signs - Pulse Rate C2D8	8.0 beats per minute (bpm) Interval -6.0 to 25.0	2.0 beats per minute (bpm) Interval -14.0 to 10.0
Change From Baseline in Vital Signs - Pulse Rate C3D1	4.0 beats per minute (bpm) Interval -25.0 to 29.0	2.0 beats per minute (bpm) Interval -34.0 to 35.0
Change From Baseline in Vital Signs - Pulse Rate C4D1	1.5 beats per minute (bpm) Interval -20.0 to 24.0	4.0 beats per minute (bpm) Interval -28.0 to 48.0
Change From Baseline in Vital Signs - Pulse Rate C5D1	0.0 beats per minute (bpm) Interval -27.0 to 16.0	2.5 beats per minute (bpm) Interval -40.0 to 26.0
Change From Baseline in Vital Signs - Pulse Rate C6D1	-3.5 beats per minute (bpm) Interval -27.0 to 35.0	3.5 beats per minute (bpm) Interval -32.0 to 35.0
Change From Baseline in Vital Signs - Pulse Rate C7D1	1.0 beats per minute (bpm) Interval -26.0 to 20.0	1.0 beats per minute (bpm) Interval -42.0 to 34.0
Change From Baseline in Vital Signs - Pulse Rate C8D1	-6.5 beats per minute (bpm) Interval -34.0 to 13.0	-1.0 beats per minute (bpm) Interval -40.0 to 46.0
Change From Baseline in Vital Signs - Pulse Rate C9D1	-1.5 beats per minute (bpm) Interval -26.0 to 25.0	1.0 beats per minute (bpm) Interval -35.0 to 30.0
Change From Baseline in Vital Signs - Pulse Rate C10D1	-3.0 beats per minute (bpm) Interval -33.0 to 17.0	3.0 beats per minute (bpm) Interval -34.0 to 43.0
Change From Baseline in Vital Signs - Pulse Rate C11D1	-2.0 beats per minute (bpm) Interval -30.0 to 22.0	3.0 beats per minute (bpm) Interval -37.0 to 41.0
Change From Baseline in Vital Signs - Pulse Rate C12D1	-6.0 beats per minute (bpm) Interval -33.0 to 5.0	1.5 beats per minute (bpm) Interval -23.0 to 33.0
Change From Baseline in Vital Signs - Pulse Rate C13D1	-1.5 beats per minute (bpm) Interval -33.0 to 25.0	2.0 beats per minute (bpm) Interval -28.0 to 44.0
Change From Baseline in Vital Signs - Pulse Rate C14D1	1.5 beats per minute (bpm) Interval -32.0 to 29.0	5.0 beats per minute (bpm) Interval -37.0 to 45.0
Change From Baseline in Vital Signs - Pulse Rate C15D1	-4.5 beats per minute (bpm) Interval -31.0 to 42.0	-3.0 beats per minute (bpm) Interval -31.0 to 32.0
Change From Baseline in Vital Signs - Pulse Rate C16D1	-1.0 beats per minute (bpm) Interval -18.0 to 30.0	1.5 beats per minute (bpm) Interval -36.0 to 40.0
Change From Baseline in Vital Signs - Pulse Rate C17D1	-6.0 beats per minute (bpm) Interval -38.0 to 32.0	1.5 beats per minute (bpm) Interval -32.0 to 41.0
Change From Baseline in Vital Signs - Pulse Rate C18D1	0.0 beats per minute (bpm) Interval -30.0 to 21.0	3.0 beats per minute (bpm) Interval -37.0 to 41.0
Change From Baseline in Vital Signs - Pulse Rate C19D1	-1.0 beats per minute (bpm) Interval -28.0 to 29.0	-3.0 beats per minute (bpm) Interval -43.0 to 22.0
Change From Baseline in Vital Signs - Pulse Rate C20D1	2.0 beats per minute (bpm) Interval -30.0 to 26.0	1.0 beats per minute (bpm) Interval -35.0 to 24.0
Change From Baseline in Vital Signs - Pulse Rate C21D1	-1.5 beats per minute (bpm) Interval -21.0 to 24.0	2.5 beats per minute (bpm) Interval -31.0 to 59.0
Change From Baseline in Vital Signs - Pulse Rate C22D1	0.0 beats per minute (bpm) Interval -12.0 to 27.0	-6.0 beats per minute (bpm) Interval -33.0 to 20.0
Change From Baseline in Vital Signs - Pulse Rate C23D1	2.0 beats per minute (bpm) Interval -20.0 to 17.0	-3.0 beats per minute (bpm) Interval -33.0 to 24.0
Change From Baseline in Vital Signs - Pulse Rate C24D1	-3.5 beats per minute (bpm) Interval -25.0 to 12.0	0.0 beats per minute (bpm) Interval -30.0 to 25.0
Change From Baseline in Vital Signs - Pulse Rate C25D1	0.0 beats per minute (bpm) Interval -15.0 to 16.0	-4.5 beats per minute (bpm) Interval -29.0 to 18.0
Change From Baseline in Vital Signs - Pulse Rate C26D1	-4.0 beats per minute (bpm) Interval -25.0 to 17.0	-3.0 beats per minute (bpm) Interval -30.0 to 19.0
Change From Baseline in Vital Signs - Pulse Rate C27D1	1.5 beats per minute (bpm) Interval -11.0 to 11.0	0.5 beats per minute (bpm) Interval -28.0 to 19.0
Change From Baseline in Vital Signs - Pulse Rate C28D1	-8.5 beats per minute (bpm) Interval -21.0 to 9.0	0.5 beats per minute (bpm) Interval -29.0 to 34.0
Change From Baseline in Vital Signs - Pulse Rate C29D1	-6.0 beats per minute (bpm) Interval -17.0 to 12.0	-4.0 beats per minute (bpm) Interval -31.0 to 22.0
Change From Baseline in Vital Signs - Pulse Rate C30D1	-3.0 beats per minute (bpm) Interval -16.0 to 17.0	-2.0 beats per minute (bpm) Interval -26.0 to 17.0
Change From Baseline in Vital Signs - Pulse Rate C31D1	1.5 beats per minute (bpm) Interval -22.0 to 11.0	-3.5 beats per minute (bpm) Interval -20.0 to 24.0
Change From Baseline in Vital Signs - Pulse Rate C32D1	2.0 beats per minute (bpm) Interval -22.0 to 12.0	2.0 beats per minute (bpm) Interval -32.0 to 38.0
Change From Baseline in Vital Signs - Pulse Rate C33D1	-4.0 beats per minute (bpm) Interval -26.0 to 13.0	1.0 beats per minute (bpm) Interval -25.0 to 14.0
Change From Baseline in Vital Signs - Pulse Rate C34D1	-1.0 beats per minute (bpm) Interval -25.0 to 38.0	1.0 beats per minute (bpm) Interval -19.0 to 14.0
Change From Baseline in Vital Signs - Pulse Rate C35D1	-2.0 beats per minute (bpm) Interval -27.0 to 21.0	2.5 beats per minute (bpm) Interval -19.0 to 27.0
Change From Baseline in Vital Signs - Pulse Rate C36D1	1.0 beats per minute (bpm) Interval -20.0 to 14.0	0.0 beats per minute (bpm) Interval -19.0 to 28.0
Change From Baseline in Vital Signs - Pulse Rate C37D1	1.5 beats per minute (bpm) Interval -26.0 to 19.0	0.0 beats per minute (bpm) Interval -14.0 to 24.0
Change From Baseline in Vital Signs - Pulse Rate C38D1	-1.0 beats per minute (bpm) Interval -24.0 to 26.0	2.0 beats per minute (bpm) Interval -16.0 to 24.0
Change From Baseline in Vital Signs - Pulse Rate C39D1	0.0 beats per minute (bpm) Interval -24.0 to 12.0	-1.0 beats per minute (bpm) Interval -13.0 to 23.0
Change From Baseline in Vital Signs - Pulse Rate C40D1	-3.0 beats per minute (bpm) Interval -29.0 to 24.0	2.5 beats per minute (bpm) Interval -18.0 to 25.0
Change From Baseline in Vital Signs - Pulse Rate C41D1	-5.0 beats per minute (bpm) Interval -28.0 to 21.0	1.0 beats per minute (bpm) Interval -18.0 to 17.0
Change From Baseline in Vital Signs - Pulse Rate C42D1	-3.0 beats per minute (bpm) Interval -24.0 to 12.0	0.0 beats per minute (bpm) Interval -17.0 to 14.0
Change From Baseline in Vital Signs - Pulse Rate C45D1	2.5 beats per minute (bpm) Interval -12.0 to 18.0	9.5 beats per minute (bpm) Interval -8.0 to 18.0
Change From Baseline in Vital Signs - Pulse Rate C46D1	1.0 beats per minute (bpm) Interval -16.0 to 25.0	11.5 beats per minute (bpm) Interval -4.0 to 22.0
Change From Baseline in Vital Signs - Pulse Rate C47D1	5.0 beats per minute (bpm) Interval -7.0 to 35.0	5.5 beats per minute (bpm) Interval -5.0 to 24.0
Change From Baseline in Vital Signs - Pulse Rate C48D1	-3.0 beats per minute (bpm) Interval -20.0 to 29.0	4.5 beats per minute (bpm) Interval -13.0 to 16.0
Change From Baseline in Vital Signs - Pulse Rate C49D1	10.0 beats per minute (bpm) Interval -14.0 to 23.0	-0.5 beats per minute (bpm) Interval -12.0 to 13.0
Change From Baseline in Vital Signs - Pulse Rate C50D1	-2.0 beats per minute (bpm) Interval -14.0 to 11.0	4.0 beats per minute (bpm) Interval -16.0 to 15.0
Change From Baseline in Vital Signs - Pulse Rate C51D1	0.0 beats per minute (bpm) Interval -8.0 to 11.0	6.0 beats per minute (bpm) Interval -4.0 to 14.0
Change From Baseline in Vital Signs - Pulse Rate C52D1	0.5 beats per minute (bpm) Interval -12.0 to 12.0	3.0 beats per minute (bpm) Interval -6.0 to 20.0
Change From Baseline in Vital Signs - Pulse Rate C53D1	6.0 beats per minute (bpm) Interval -14.0 to 11.0	10.0 beats per minute (bpm) Interval -3.0 to 17.0
Change From Baseline in Vital Signs - Pulse Rate C54D1	2.5 beats per minute (bpm) Interval -6.0 to 6.0	1.0 beats per minute (bpm) Interval -2.0 to 4.0
Change From Baseline in Vital Signs - Pulse Rate C55D1	-6.5 beats per minute (bpm) Interval -9.0 to 7.0	5.0 beats per minute (bpm) Interval 5.0 to 5.0
Change From Baseline in Vital Signs - Pulse Rate C56D1	1.5 beats per minute (bpm) Interval -10.0 to 10.0	1.0 beats per minute (bpm) Interval 1.0 to 1.0
Change From Baseline in Vital Signs - Pulse Rate C57D1	-4.0 beats per minute (bpm) Interval -17.0 to 6.0	—
Change From Baseline in Vital Signs - Pulse Rate C58D1	4.0 beats per minute (bpm) Interval -15.0 to 9.0	—
Change From Baseline in Vital Signs - Pulse Rate C59D1	2.0 beats per minute (bpm) Interval -7.0 to 11.0	—
Change From Baseline in Vital Signs - Pulse Rate C60D1	1.5 beats per minute (bpm) Interval -11.0 to 14.0	—
Change From Baseline in Vital Signs - Pulse Rate C61D1	2.0 beats per minute (bpm) Interval -8.0 to 12.0	—
Change From Baseline in Vital Signs - Pulse Rate C62D1	9.0 beats per minute (bpm) Interval -1.0 to 19.0	—
Change From Baseline in Vital Signs - Pulse Rate End of Treatment	2.5 beats per minute (bpm) Interval -32.0 to 9.0	6.5 beats per minute (bpm) Interval -25.0 to 44.0
Change From Baseline in Vital Signs - Pulse Rate Follow-up Day 30	-1.0 beats per minute (bpm) Interval -26.0 to 2.0	-2.0 beats per minute (bpm) Interval -38.0 to 51.0
Change From Baseline in Vital Signs - Pulse Rate Follow-up Day 60	2.0 beats per minute (bpm) Interval -23.0 to 29.0	3.0 beats per minute (bpm) Interval -11.0 to 43.0
Change From Baseline in Vital Signs - Pulse Rate Follow-up Day 90	9.0 beats per minute (bpm) Interval -23.0 to 11.0	5.5 beats per minute (bpm) Interval -7.0 to 50.0

SECONDARY outcome

Timeframe: Cycle 1 Day 1 up to 30 months after the first dose

Population: The population for this outcome measure included all participants who received at least 1 dose of study drug (axitinib or avelumab) and all participants who were randomized independent of whether they had received a dose of study drug.

Confirmed OR was defined as complete response (CR) or partial response (PR) according to RECIST v1.1 from the start date until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 CR	2 Participants	2 Participants
Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 PR	8 Participants	21 Participants

SECONDARY outcome

Timeframe: Cycle 1 Day 1 up to 30 months after the first dose

Population: The population for this outcome measure included all participants who received at least 1 dose of study drug (axitinib or avelumab) and all participants who were randomized independent of whether they had received a dose of study drug.

DC was defined as OR (CR or PR) or stable disease (SD) per RECIST v1.1 from the start date until the first documentation of objective disease progression or death due to any cause. SD was defined as not qualifying for CR, PR, or progression (PD). PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Number of Participants Achieving Disease Control (DC) Based on RECIST Version 1.1	15 Participants	28 Participants

SECONDARY outcome

Timeframe: Cycle 1 Day 1 up to 30 months after the first dose

Population: The population for this outcome measure included all participants who received at least 1 dose of study drug (axitinib or avelumab), all participants who were randomized independent of whether they had received a dose of study drug, and all participants who had achieved confirmed CR or PR.

DR was defined as the time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=10 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=23 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Duration of Response (DR) Based on RECIST Version 1.1	NA months Interval 4.2 to Median and upper limit were not estimable. The median DR based on the Kaplan-Meier method had not been reached at the time of data cutoff (03 April 2018).	NA months Interval 9.6 to Median and upper limit were not estimable. The median DR based on the Kaplan-Meier method had not been reached at the time of data cutoff (03 April 2018).

SECONDARY outcome

Timeframe: Cycle 1 Day 1 up to 30 months after the first dose

Population: The population for this outcome measure included all participants who received at least 1 dose of study drug (axitinib or avelumab) and all participants who were randomized independent of whether they had received a dose of study drug.

PFS was defined as defined as the time from the start date to the date of the first documentation of objective progression of disease (PD) or death due to any cause, whichever occurred first. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Progression-free Survival (PFS)	19.2 months Interval 4.4 to Upper limit was not estimable. The upper limit for PFS based on the Kaplan-Meier method had not been reached at the time of data cutoff (03 April 2018).	7.6 months Interval 4.1 to Upper limit was not estimable. The upper limit for PFS based on the Kaplan-Meier method had not been reached at the time of data cutoff (03 April 2018).

SECONDARY outcome

Timeframe: Cycle 1 Day 1 up to 30 months after the first dose

Population: The population for this outcome measure included all participants who received at least 1 dose of study drug (axitinib or avelumab), all participants who were randomized independent of whether they had received a dose of study drug, and all participants who had achieved confirmed CR or PR.

TTR was defined as the time from start date to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=10 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=23 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Time to Tumor Response (TTR) Based on RECIST Version 1.1	1.6 months Interval 1.3 to 5.8	1.4 months Interval 1.2 to 9.6

SECONDARY outcome

Timeframe: Cycle 1 Day 1 up to 30 months after the first dose

Population: The population for this outcome measure included all participants who received at least 1 dose of study drug (axitinib or avelumab) and all participants who were randomized independent of whether they had received a dose of study drug.

OS was defined as the time from the start date to the date of death due to any cause. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Overall Survival (OS)	NA months Interval 23.0 to Median and upper limit were not estimable. The median and upper limit for OS based on the Kaplan-Meier method had not been reached at the time of data cutoff (03 April 2018).	NA months Interval 20.1 to Median and upper limit were not estimable. The median and upper limit for OS based on the Kaplan-Meier method had not been reached at the time of data cutoff (03 April 2018).

SECONDARY outcome

Timeframe: Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib and who had at least 1 of the pharmacokinetic (PK) parameters of interest of either study drug.

Cmax for axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=14 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Maximum Observed Plasma Concentration (Cmax) for Axitinib When Dosed Alone and in Combination With Avelumab Lean-in Day 7	23.1947 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 178	—
Maximum Observed Plasma Concentration (Cmax) for Axitinib When Dosed Alone and in Combination With Avelumab Cycle 4 Day 1	16.5806 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 254	—

SECONDARY outcome

Timeframe: Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib and who had at least 1 of the pharmacokinetic (PK) parameters of interest of either study drug.

Tmax for axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=14 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Time for Cmax (Tmax) for Axitinib When Dosed Alone and in Combination With Avelumab Lean-in Day 7	2.0900 hours (hrs) Interval 0.017 to 4.18	—
Time for Cmax (Tmax) for Axitinib When Dosed Alone and in Combination With Avelumab Cycle 4 Day 1	1.9850 hours (hrs) Interval 1.0 to 3.02	—

SECONDARY outcome

Timeframe: Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib and who had at least 1 of the pharmacokinetic (PK) parameters of interest of either study drug.

AUCtau was defined as area under the plasma concentration time profile from time zero to time tau, the dosing interval at steady state. tau = 12 hrs for Axitinib. AUCtau for Axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm was reported. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=13 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Area Under the Plasma Concentration Time Profile From Time Zero to the Next Dose at Steady State (AUCtau) for Axitinib When Dosed Alone and in Combination With Avelumab Lean-in Day 7	113.11 nanograms*hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 206	—
Area Under the Plasma Concentration Time Profile From Time Zero to the Next Dose at Steady State (AUCtau) for Axitinib When Dosed Alone and in Combination With Avelumab Cycle 4 Day 1	95.60 nanograms*hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 162	—

SECONDARY outcome

Timeframe: Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib and who had at least 1 of the pharmacokinetic (PK) parameters of interest of either study drug.

t1/2 was calculated by Log e(2)/kel. kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time-curve. Only those data points judged to describe the terminal log linear decline were used in the regression. t1/2 for Axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm was reported. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=10 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Terminal Half-Life (t1/2) for Axitinib When Dosed Alone and in Combination With Avelumab Lean-in Day 7	2.755 hrs Standard Deviation 1.5417	—
Terminal Half-Life (t1/2) for Axitinib When Dosed Alone and in Combination With Avelumab Cycle 4 Day 1	3.252 hrs Standard Deviation 1.3389	—

SECONDARY outcome

Timeframe: Predose on Day 1 of Cycles 1, 2, 3, 4, 6, 8, 14, 20, 26, 32, 38, 44, and 50

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib and who had at least 1 of the pharmacokinetic (PK) parameters of interest of either study drug.

Ctrough was directly observed from data. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=54 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab C14D1	36.1 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 59	—
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab C20D1	41.0 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 60	—
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab Cycle 1 Day 1 (C1D1)	1.0 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 181	—
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab C2D1	20.3 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 82	—
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab C3D1	23.9 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 151	—
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab C4D1	23.4 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 103	—
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab C6D1	26.3 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 134	—
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab C8D1	28.3 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 106	—
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab C26D1	38.4 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 77	—
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab C32D1	40.8 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 72	—
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab C38D1	44.5 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 68	—
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab C44D1	67.5 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 52	—
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab C50D1	40.5 microgram per milliliter (ug/mL) Geometric Coefficient of Variation 121	—

SECONDARY outcome

Timeframe: Predose, 1 hour, and 168 hours post dose on Cycle 1 Day 1; predose and 1 hour post dose on Cycle 4 Day 1

Population: The population for this outcome measure included all enrolled participants who received at least 1 dose of avelumab or axitinib and who had at least 1 of the pharmacokinetic (PK) parameters of interest of either study drug.

Cmax for avelumab on Cycle 1 Day (C1D1) and C1D4 were reported. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=54 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Cmax for Avelumab C4D1	278.0 ug/mL Geometric Coefficient of Variation 60	—
Cmax for Avelumab C1D1	233.4 ug/mL Geometric Coefficient of Variation 27	—

SECONDARY outcome

Timeframe: Baseline

Population: The population for this outcome measure included all enrolled participants who had at least 1 screening biomarker assessment and who received at least 1 dose of avelumab or axitinib.

Number of participants with PD-L1 positive (PD-L1 >=1%) status in immune cell (IC), tumor cell (TC), or both IC and TC. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=16 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline IC	11 Participants	30 Participants
Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline TC	3 Participants	15 Participants
Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline IC+TC	11 Participants	32 Participants

SECONDARY outcome

Timeframe: Pre-dose on Day 1 of Cycles 1-4, 6, 8, then every 12 weeks thereafter until Cycle 50, and on Follow-up Day 30 (maximum of 2 years)

Population: The analysis population (ie, Number of Participants Analyzed)=number of participants (#p) received at least 1 dose of study drug and with at least 1 ADA sample collected. Number Analyzed =Number of Participants Analyzed for ADA\_p and ADA\_n; = #p with valid baseline ADA result for ADA\_bp; = #p with valid baseline and at least 1 valid post-baseline ADA results for Tb\_ADA; = #p with at least 1 valid post-baseline ADA result and without positive baseline ADA result for Ti\_ADA, t\_ADA, and p\_ADA.

Whole blood specimens were collected at the designated times (Day 1 of Cycles 1-4, 6, and 8, then every 12 weeks until Cycle 50, and Follow-up Day 30) to provide serum for evaluation of avelumab immunogenicity. Human serum ADA specimens were analyzed for the presence or absence of anti-avelumab antibodies with quasi-quantitative enzyme-linked immunosorbent assay, following a tiered approach using screening, confirmation and titer/quantitation. ADA serum specimens were screened at tier 1. In the event that there were no positive specimens, no further analyses were to be conducted. If positive specimens were identified, these specimens were further tested with the confirmatory assay to confirm as positive. Number of participants with ADA positive at baseline, ADA never-positive, ADA ever-positive, treatment-boosted ADA, treatment-induced ADA, transient ADA response, or persistent ADA response from baseline up to 2 years. The results reflect data available on cutoff of PCD (03 Apr 2018).

Outcome measures

Measure	Axitinib + Avelumab With Lead-in n=15 Participants Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 Participants Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status ADA positive at baseline (ADA_bp)	2 Participants	0 Participants
Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status ADA never-positive (ADA_n)	12 Participants	31 Participants
Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status ADA ever-positive (ADA_p)	3 Participants	8 Participants
Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status Treatment-boosted ADA (Tb_ADA)	0 Participants	0 Participants
Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status Treatment-induced ADA (Ti_ADA)	1 Participants	8 Participants
Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status Transient ADA response (t_ADA)	0 Participants	5 Participants
Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status Persistent ADA response (p_ADA)	1 Participants	3 Participants

Adverse Events

Axitinib + Avelumab With Lead-in

Serious events: 6 serious events

Other events: 16 other events

Deaths: 6 deaths

Axitinib + Avelumab

Serious events: 18 serious events

Other events: 39 other events

Deaths: 14 deaths

Serious adverse events

Measure	Axitinib + Avelumab With Lead-in n=16 participants at risk Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 participants at risk Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Blood and lymphatic system disorders Anaemia	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Neutropenia	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Myocarditis	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Palpitations	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Tachycardia	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Endocrine disorders Adrenal insufficiency	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Diarrhoea	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Nausea	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Vomiting	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Adverse drug reaction	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Disease progression	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Pyrexia	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Sepsis	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Tooth abscess	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Alanine aminotransferase increased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Amylase increased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Aspartate aminotransferase increased	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Lipase increased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Dehydration	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Presyncope	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Spinal cord compression	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Hypoxia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Vascular disorders Haematoma	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Vascular disorders Haemorrhage	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Vascular disorders Venous thrombosis	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Pancreatitis	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Immune system disorders Anaphylactic shock	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Substance-induced psychotic disorder	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Renal and urinary disorders Haematuria	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.

Other adverse events

Measure	Axitinib + Avelumab With Lead-in n=16 participants at risk Participants received 5 mg axitinib tablets orally twice daily for 7 days in lead-in period (7 days) followed by 10 milligram/ kilogram (mg/kg) avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 255.4 weeks).	Axitinib + Avelumab n=39 participants at risk Participants received 10 mg/kg avelumab intravenously every 2 weeks along with 5 mg axitinib tablets orally twice daily, on Day 1 of each treatment cycle (duration of each cycle=14 days) in treatment period (up to maximum of 240.1 weeks).
Vascular disorders Haematoma	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Anaemia	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	12.8% 5/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Leukocytosis	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Leukopenia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Lymphopenia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Palpitations	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Sinus bradycardia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Sinus tachycardia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Ventricular arrhythmia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Ear and labyrinth disorders Ear discomfort	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Ear and labyrinth disorders Hypoacusis	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Endocrine disorders Hyperthyroidism	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Endocrine disorders Hypothyroidism	25.0% 4/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	28.2% 11/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Eye disorders Dry eye	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Eye disorders Eye haemorrhage	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Eye disorders Eyelid irritation	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Eye disorders Vision blurred	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Abdominal discomfort	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Abdominal pain	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 6/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Abdominal pain upper	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Anal haemorrhage	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Constipation	50.0% 8/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	30.8% 12/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Dental caries	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	10.3% 4/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Diarrhoea	81.2% 13/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	66.7% 26/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Diverticulum	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Dry mouth	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	12.8% 5/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Dyspepsia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Flatulence	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Gastrooesophageal reflux disease	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	12.8% 5/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Gingival hypertrophy	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Lip pain	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Mouth ulceration	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Nausea	43.8% 7/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	20.5% 8/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Oral pain	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Rectal haemorrhage	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Stomatitis	25.0% 4/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	10.3% 4/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Tongue discomfort	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Toothache	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Vomiting	25.0% 4/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	25.6% 10/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Axillary pain	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Chest discomfort	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Chest pain	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Chills	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	17.9% 7/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Fatigue	62.5% 10/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	51.3% 20/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Feeling abnormal	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Feeling cold	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Gait disturbance	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Malaise	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Mucosal inflammation	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	28.2% 11/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Oedema	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Oedema peripheral	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 6/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Pain	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	10.3% 4/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Peripheral swelling	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Pyrexia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	12.8% 5/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Cellulitis	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Lower respiratory tract infection	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Nasopharyngitis	25.0% 4/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	12.8% 5/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Rhinitis	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Sinusitis	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Tooth infection	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Upper respiratory tract infection	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	17.9% 7/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Urinary tract infection	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	12.8% 5/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Viral infection	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Viral upper respiratory tract infection	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Contusion	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Epicondylitis	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Fall	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Infusion related reaction	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	20.5% 8/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Procedural pain	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Alanine aminotransferase increased	37.5% 6/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	30.8% 12/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Amylase increased	56.2% 9/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	25.6% 10/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Aspartate aminotransferase increased	25.0% 4/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	35.9% 14/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood alkaline phosphatase increased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 6/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood bilirubin increased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood cholesterol increased	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood corticotrophin decreased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood creatine phosphokinase increased	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood creatinine increased	31.2% 5/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	10.3% 4/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood lactate dehydrogenase increased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood magnesium decreased	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood phosphorus decreased	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood sodium decreased	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood thyroid stimulating hormone decreased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood thyroid stimulating hormone increased	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood triglycerides increased	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood uric acid increased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations C-reactive protein increased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Cardiac murmur	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Ejection fraction decreased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Gamma-glutamyltransferase increased	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	10.3% 4/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Haemoglobin increased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Lipase increased	37.5% 6/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	17.9% 7/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Lymphocyte count decreased	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Platelet count decreased	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	10.3% 4/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Weight decreased	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	23.1% 9/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Weight increased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Decreased appetite	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	25.6% 10/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Dehydration	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Gout	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hypercalcaemia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hyperglycaemia	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hyperkalaemia	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	10.3% 4/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hypernatraemia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hypertriglyceridaemia	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	10.3% 4/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hyperuricaemia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 6/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hypoalbuminaemia	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	12.8% 5/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hyponatraemia	31.2% 5/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	12.8% 5/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hypophosphataemia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	20.5% 8/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Arthralgia	43.8% 7/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	30.8% 12/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Back pain	25.0% 4/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	12.8% 5/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Flank pain	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Joint swelling	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Muscle spasms	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	17.9% 7/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Muscular weakness	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Myalgia	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	20.5% 8/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Pain in extremity	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	10.3% 4/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Ataxia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Dizziness	31.2% 5/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	10.3% 4/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Dysgeusia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 6/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Headache	43.8% 7/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	20.5% 8/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Hyperaesthesia	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Hypoaesthesia	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Lethargy	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Paraesthesia	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Tremor	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Confusional state	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Dysphoria	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Insomnia	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 6/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Mood altered	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Renal and urinary disorders Dysuria	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Renal and urinary disorders Proteinuria	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 6/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Renal and urinary disorders Urinary incontinence	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Reproductive system and breast disorders Balanoposthitis	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Reproductive system and breast disorders Breast mass	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Reproductive system and breast disorders Erectile dysfunction	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Reproductive system and breast disorders Testicular swelling	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Cough	43.8% 7/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	25.6% 10/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Dysphonia	43.8% 7/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	51.3% 20/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Dyspnoea	37.5% 6/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	30.8% 12/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Hypoxia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	10.3% 4/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	12.8% 5/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Productive cough	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Wheezing	18.8% 3/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Dry skin	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	10.3% 4/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Eczema	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Hyperkeratosis	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Ingrowing nail	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Night sweats	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	43.8% 7/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	30.8% 12/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Pruritus	25.0% 4/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	25.6% 10/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Rash	37.5% 6/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	38.5% 15/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Rash erythematous	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Rash macular	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Rash papular	12.5% 2/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Rash pruritic	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Skin exfoliation	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Skin lesion	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 6/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Vascular disorders Hypertension	50.0% 8/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	48.7% 19/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Vascular disorders Hypotension	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	12.8% 5/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Ear and labyrinth disorders Ear congestion	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Eye disorders Blepharitis	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Haemorrhoids	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Hyperaesthesia teeth	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Retching	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Immune system disorders Multiple allergies	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Eye infection	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Gingivitis	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Hordeolum	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Eye contusion	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Incisional hernia	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Activated partial thromboplastin time prolonged	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood corticotrophin increased	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations White blood cell count decreased	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hyperlipidaemia	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Gouty arthritis	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Cognitive disorder	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Neurotoxicity	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Taste disorder	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Actinic keratosis	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	5.1% 2/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 3/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Scar pain	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Renal and urinary disorders Haematuria	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.6% 1/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Defaecation urgency	6.2% 1/16 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/39 • Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER