Trial Outcomes & Findings for A Dose Finding Study To Evaluate Safety, Drug Interaction, Tumor Markers Of Axitinib In Combination With MK-3475 In Adult Patients With Previously Untreated Advanced Renal Cell Cancer (NCT NCT02133742)

Last Updated: 2021-07-28

Results Overview

DLT was defined as any of the following adverse events (AEs) occurring in the first two cycles of treatment which were attributable to one or both the study drugs: 1) Grade 4 neutropenia, 2) Febrile neutropenia lasting greater than (\>) 1 hour, 3) Grade greater than or equal to (\>=) 3 neutropenia with infection, 4) Grade \>=3 thrombocytopenia with bleeding, 4) Grade 4 thrombocytopenia, 5) Any grade \>=3 non-hematologic: non-laboratory toxicities despite maximum supportive therapy or hypertension despite maximal medical therapy, 6) Grade \>=3 non-hematologic toxicities resulted in hospitalisation or medical intervention 7) Inability to complete at least 75 percent (%) of axitinib dosing or 2 infusions of pembrolizumab within the DLT observation period (up to 42 days) due to treatment related toxicity. Severity of AEs was graded according to NCI (National Cancer Institute) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

52 participants

Primary outcome timeframe

Cycle 1 Day 1 to Cycle 2 Day 21 (up to 42 days)

Results posted on

2021-07-28

Participant Flow

This study was planned to be conducted in two potential doses in the dose finding phase, Axitinib 3 mg + Pembrolizumab (MK-3475) 2 mg and Axitinib 5 mg + MK 3475 2 mg. However, no participant was enrolled in the Axitinib 3 mg + MK-3475 2 mg reporting group and all participants were enrolled in ''Axitinib 5 mg + MK-3475 2 mg'' reporting group only.

Participant milestones

Participant milestones
Measure	Axitinib 5 mg + Pembrolizumab (MK-3475) 2 mg Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days). Participants received axitinib up to a maximum of 64 cycles and pembrolizumab up to 56 cycles in dose expansion phase (each cycle of 21 days) until documented disease progression or unacceptable toxicity or study discontinuation criteria were met.
Period 1: Dose Finding Phase (6 Months) STARTED	11
Period 1: Dose Finding Phase (6 Months) COMPLETED	11
Period 1: Dose Finding Phase (6 Months) NOT COMPLETED	0
Period 2:Dose Expansion Phase (1344days) STARTED	52
Period 2:Dose Expansion Phase (1344days) COMPLETED	0
Period 2:Dose Expansion Phase (1344days) NOT COMPLETED	52

Reasons for withdrawal

Reasons for withdrawal
Measure	Axitinib 5 mg + Pembrolizumab (MK-3475) 2 mg Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days). Participants received axitinib up to a maximum of 64 cycles and pembrolizumab up to 56 cycles in dose expansion phase (each cycle of 21 days) until documented disease progression or unacceptable toxicity or study discontinuation criteria were met.
Period 2:Dose Expansion Phase (1344days) Lost to Follow-up	2
Period 2:Dose Expansion Phase (1344days) End of survival follow-up/treatment	31
Period 2:Dose Expansion Phase (1344days) Death	13
Period 2:Dose Expansion Phase (1344days) Participant refused further follow-up	5
Period 2:Dose Expansion Phase (1344days) Adverse Event	1

Baseline Characteristics

A Dose Finding Study To Evaluate Safety, Drug Interaction, Tumor Markers Of Axitinib In Combination With MK-3475 In Adult Patients With Previously Untreated Advanced Renal Cell Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Axitinib 5 mg + Pembrolizumab (MK-3475) 2 mg n=52 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days). Participants received axitinib up to a maximum of 64 cycles and pembrolizumab up to 56 cycles in dose expansion phase (each cycle of 21 days) until documented disease progression or unacceptable toxicity or study discontinuation criteria were met.
Age, Continuous	61.2 years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants
Race/Ethnicity, Customized White	45 Participants n=5 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	4 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1 Day 1 to Cycle 2 Day 21 (up to 42 days)

Population: Per protocol analysis set included all enrolled eligible participants who received at least 1 dose of axitinib or pembrolizumab and experienced DLT during first 2 cycles, or complete the observation period for first 2 cycles of treatment. Here, number of participant analyzed (N) = number of participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=11 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Number of Participants With Dose-Limiting Toxicities (DLT): Dose Finding Phase	3 Participants

SECONDARY outcome

Timeframe: Baseline up to 28 days after last dose of study drug (approximately up to 1552 days)

Population: Safety analysis set included all enrolled participants who received at least one dose of axitinib or pembrolizumab.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=52 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	52 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	29 Participants

SECONDARY outcome

Timeframe: Baseline up to 28 days after last dose of study drug (approximately up to 1552 days)

Population: Safety analysis set included all enrolled participants who received at least one dose of axitinib or pembrolizumab.

An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=52 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	52 Participants
Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	23 Participants

SECONDARY outcome

Timeframe: Baseline up to 28 days after last dose of study drug (approximately up to 1552 days)

Population: Safety analysis set included all enrolled participants who received at least one dose of axitinib or pembrolizumab.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs were graded according to the Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA) as Grade 3: Severe, Grade 4: Life threatening, Grade 5: Death related to AE. Participants were counted once according to the maximum grade observed.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=52 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Number of Participants With Adverse Events (AEs) According to Severity of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03 Grade 3 or 4	38 Participants
Number of Participants With Adverse Events (AEs) According to Severity of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03 Grade 5	1 Participants

SECONDARY outcome

Timeframe: Baseline up to a maximum of 1083 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of axitinib or pembrolizumab.

Laboratory parameters included hematological and biochemistry parameters. Biochemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin (total), creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. Hematology parameters included anemia, haemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets and white blood cells. Test abnormalities were graded by NCI CTCAE version 4.03 as Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Only categories with at least 1 participant with abnormality are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=52 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Hematology Alanine aminotransferase: Grade 3	2 Participants
Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Hematology Hypercalcemia: Grade 3	1 Participants
Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Hematology Hyperglycemia: Grade 3	5 Participants
Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Hematology Hyperkalemia: Grade 3	1 Participants
Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Hematology Hypermagnesemia; Grade 3	1 Participants
Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Hematology Hypokalemia: Grade 3	3 Participants
Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Hematology Hyponatremia: Grade 3	4 Participants
Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Hematology Hypophosphatemia: Grade 3	7 Participants
Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Hematology Lymphopenia: Grade 3	4 Participants
Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Hematology Neutrophils (absolute): Grade 3	2 Participants

SECONDARY outcome

Timeframe: Baseline up to a maximum of 1083 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of axitinib or pembrolizumab.

Urinalysis parameter included urine protein, urine blood/hemoglobin and urine glucose. Test abnormalities was defined as deviation from normal range. Normal range of 24-hour urine protein test: less than 150 mg of protein per day, urine glucose: 0 to 0.8 mmol/L (millimoles per liter), urine protein: 0 to 20 mg/dL (milligrams per deciliter). Urine blood/hemoglobin abnormality was defined as presence and absence of blood/hemoglobin in urine of participants.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=52 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Number of Participants With Laboratory Test Abnormalities: Urinalysis Urine protein (24 hrs)	0 Participants
Number of Participants With Laboratory Test Abnormalities: Urinalysis Urine blood/hemoglobin	11 Participants
Number of Participants With Laboratory Test Abnormalities: Urinalysis Urine glucose	9 Participants
Number of Participants With Laboratory Test Abnormalities: Urinalysis Urine protein	25 Participants

SECONDARY outcome

Timeframe: Baseline up to a maximum of 1083 days

Population: Safety analysis set included all enrolled participants who received at least 1 dose of axitinib or pembrolizumab.

Vital signs included blood pressure, pulse rate and weight. Change from baseline values were considered to be clinically significant based on investigator's judgement.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=52 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Cycle 43 (up to 1083 days)

Population: Safety analysis set included all enrolled participants who received at least 1 dose of axitinib or pembrolizumab.

ECOG performance status was used to assess how disease affect the daily living abilities of a participant. It was measured on a scale ranging from 0 to 4, where 0=fully active (able to carry on all pre-disease activities without restriction); 1=restricted in physically strenuous activity but ambulatory (able to carry out light/sedentary work); 2=ambulatory and capable of all self-care but unable to carry out any work activities (for more than 50% of waking hours); 3=capable of limited self-care, confined to bed or chair (for \>50% of waking hours); 4=completely disabled, not capable of any self-care, totally confined to bed or chair. Higher scores signified =more functional impairment of a participant.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=52 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Number of Participants With Eastern Cooperative Oncology Group [ECOG] Performance Status Score 0	39 Participants
Number of Participants With Eastern Cooperative Oncology Group [ECOG] Performance Status Score 1	10 Participants
Number of Participants With Eastern Cooperative Oncology Group [ECOG] Performance Status Score 2	0 Participants
Number of Participants With Eastern Cooperative Oncology Group [ECOG] Performance Status Score 3	0 Participants
Number of Participants With Eastern Cooperative Oncology Group [ECOG] Performance Status Score 4	0 Participants
Number of Participants With Eastern Cooperative Oncology Group [ECOG] Performance Status Score Missing	3 Participants

SECONDARY outcome

Timeframe: Baseline until disease progression or death due to any cause, up to a maximum of 1083 days

Population: Response evaluable analysis set included all participants who received study treatment with an adequate baseline tumor assessment (using standard RECIST version 1.1 criteria).

Objective response rate was defined as percentage of participants with confirmed complete response (CR) or confirmed partial response (PR), as assessed by response evaluation criteria in solid tumors (RECIST) version 1.1. Confirmed responses were those that persist on repeated imaging for at least 4 weeks after initial documentation of response. CR was defined as disappearance of all target lesions and the reduction in short axis of any pathological lymph nodes to \<10 mm. PR was defined as a 30% or more decrease in the sum of longest dimensions of the target lesions, taking as reference the baseline sum of longest dimensions.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=52 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Objective Response Rate	73.1 percentage of participants Interval 59.0 to 84.4

SECONDARY outcome

Timeframe: Baseline until disease progression or death due to any cause, up to a maximum of 1083 days

Population: Response evaluable analysis set included all participants who received study treatment with an adequate baseline tumor assessment (using standard RECIST version 1.1 criteria). Here, "N" signifies number of participants who were evaluable for this outcome measure.

DR:date of first documentation of objective tumour response(OR) confirmed to date of first documentation of PD/death due to any cause,whichever occurred first.PD per RECIST 1.1:\>=20%increase in sum of longest dimensions(LD) of target lesions,reference to smallest sum of LD recorded since treatment started/appearance of 1 or more new lesions/increase of at least 5mm addition to relative increase of 20%.DR calculated only for participants with confirmed OR.Participants lacking evaluation of tumour response after date of first study drug dose was censored on date of first dose unless death occurred prior to 18 weeks.If participants had at least 1 on-study assessment,PFS was censored on date of last evaluable tumour disease assessment documenting absence of PD for participants who were alive and progression free at time of analysis/had documentation of PD/death after\>=2 consecutive missed tumour assessments/given anti-tumour treatment other than study drug prior to documented PD/death.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=38 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Duration of Response (DR)	18.6 months Interval 15.1 to Number of participants with a confirmed objective response who subsequently progressed is too small to provide such summary statistics.

SECONDARY outcome

Timeframe: Baseline until disease progression or death due to any cause, up to a maximum of 1083 days

TTR was defined as the time from first dose of study treatment to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=38 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Time to Response (TTR)	2.8 months Interval 0.7 to 15.2

SECONDARY outcome

Timeframe: Baseline until disease progression or death due to any cause, up to a maximum of 1083 days

Population: Response evaluable analysis set included all participants who received study treatment with an adequate baseline tumor assessment (using standard RECIST version 1.1 criteria).

PFS: time from date of first dose of study drug to the date of first documented PD or death on study due to any cause. PD as per RECIST v1.1 defined as at least a 20% increase in sum of longest dimensions of target lesions, reference to smallest sum of longest dimensions recorded since treatment started, or appearance of 1 or more new lesions or increase of at least 5 mm in addition to relative increase of 20%. Participants lacking an evaluation of tumor response after date of first study drug dose had event time censored on date of first dose unless death occurred prior to 18 weeks. If participants had at least 1 on-study assessment, PFS data was censored on date of last evaluable tumor disease assessment documenting absence of PD for participants who were alive and progression free at the time of analysis or had documentation of PD or had death after \>=2 consecutive missed tumor assessments or were given anti-tumor treatment other than study drug prior to documented PD or death.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=52 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Progression-Free Survival (PFS)	20.9 months Interval 15.4 to Upper limit of 95% CI was not reached since a large proportion of participants in the analysis set had their PFS data censored and there were insufficient number of participants with events to calculate the full 95% CI.

SECONDARY outcome

Timeframe: Baseline until disease progression or death due to any cause, up to a maximum of 1552 days

Population: Response evaluable analysis set included all participants who received study treatment with an adequate baseline tumor assessment (using standard RECIST version 1.1 criteria).

OS was defined as the time from the first dose of study drug to the date of death due to any cause. For participants still alive at the time of analysis, the OS time was censored on the last date the participants were known to be alive.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=52 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Overall Survival (OS)	NA months Interval 43.7 to Median and upper limit for 95% CI could not be estimated because there were insufficient number of participants with event.

SECONDARY outcome

Timeframe: Dose Finding Phase:Pre-dose,1,2,3,4,6,8 hours (hrs) post-dose on Day 7 of Lead-in (7 days prior Cycle 1 Day 1), Cycle 7 Day 1;Dose Expansion Phase:Pre dose,1,2,3,4,6,8 hrs post dose on Day 7 of Lead-in (7 days prior Cycle 1 Day 1), Cycle 7 Day 1

Population: Pharmacokinetic (PK) parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest of any of the study drugs. Here "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure and "Number Analyzed" = participants evaluable for specific rows.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=10 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Maximum Observed Plasma Concentration (Cmax) of Axitinib Dose finding phase: Day 7 of Lead-in	46.58 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 58
Maximum Observed Plasma Concentration (Cmax) of Axitinib Dose finding phase: Day 1 of cycle 7	36.57 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 31
Maximum Observed Plasma Concentration (Cmax) of Axitinib Dose expansion phase: Day 7 of Lead-in	24.83 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 85
Maximum Observed Plasma Concentration (Cmax) of Axitinib Dose expansion phase: Day 1 of cycle 7	22.65 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 51

SECONDARY outcome

Timeframe: Dose Finding Phase:Pre-dose, 1, 2, 3, 4, 6, 8 hrs post-dose on Day 7 of Lead-in (7 days prior Cycle 1 Day 1), Cycle 7 Day 1; Dose Expansion Phase:Pre-dose, 1, 2, 3, 4, 6, 8 hrs post-dose on Day 7 of Lead-in (7 days prior Cycle 1 Day 1), Cycle 7 Day 1

Population: PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest of any of the study drugs. Here "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure and "Number Analyzed" = participants evaluable for specific rows.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=10 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Axitinib Dose finding phase: Day 7 of Lead-in	2.00 hour Interval 1.0 to 4.0
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Axitinib Dose finding phase: Day 1 of cycle 7	3.00 hour Interval 3.0 to 4.0
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Axitinib Dose expansion phase: Day 7 of Lead-in	2.00 hour Interval 0.0 to 3.0
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Axitinib Dose expansion phase: Day 1 of cycle 7	2.00 hour Interval 1.0 to 4.0

SECONDARY outcome

Timeframe: Dose Finding Phase:Pre-dose, 1, 2, 3, 4,6,8, 12 hrs post-dose on Day 7 of Lead-in (7 days prior Cycle 1 Day 1), Cycle 7 Day 1; Dose Expansion Phase:Pre-dose, 1,2,3,4,6,8,12 hrs post-dose on Day 7 of Lead-in (7 days prior Cycle 1 Day 1), Cycle 7 Day 1

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=10 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC 0-12) of Axitinib Dose finding phase: Day 7 of Lead-in	199.1 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 46
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC 0-12) of Axitinib Dose finding phase: Day 1 of cycle 7	219.4 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 12
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC 0-12) of Axitinib Dose expansion phase: Day 7 of Lead-in	92.99 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 142
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC 0-12) of Axitinib Dose expansion phase: Day 1 of cycle 7	116.9 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 50

SECONDARY outcome

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes).

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=10 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Apparent Oral Clearance (CL/F) of Axitinib Dose finding phase: Day 7 of Lead-in	25.11 liter per hour (L/hr) Geometric Coefficient of Variation 46
Apparent Oral Clearance (CL/F) of Axitinib Dose finding phase: Day 1 of cycle 7	22.79 liter per hour (L/hr) Geometric Coefficient of Variation 12
Apparent Oral Clearance (CL/F) of Axitinib Dose Expansion Phase: Day 7 of Lead-in	53.77 liter per hour (L/hr) Geometric Coefficient of Variation 142
Apparent Oral Clearance (CL/F) of Axitinib Dose expansion phase: Day 1 of cycle 7	42.79 liter per hour (L/hr) Geometric Coefficient of Variation 50

SECONDARY outcome

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=6 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Apparent Volume of Distribution (Vz/F) of Axitinib Dose finding phase: Day 7 of Lead-in	85.12 liter Geometric Coefficient of Variation 36
Apparent Volume of Distribution (Vz/F) of Axitinib Dose finding phase: Day 1 of cycle 7	50.91 liter
Apparent Volume of Distribution (Vz/F) of Axitinib Dose Expansion Phase: Day 7 of Lead-in	245.8 liter Geometric Coefficient of Variation 50
Apparent Volume of Distribution (Vz/F) of Axitinib Dose expansion phase: Day 1 of cycle 7	225.5 liter

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 up to Day 21 of Cycle 56 (up to 1176 days)

Population: PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest of any of the study drugs.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=52 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Number of Participants With Positive Anti-Drug Antibodies (ADA) of Pembrolizumab (MK-3475)	3 Participants

SECONDARY outcome

Timeframe: Baseline up to Cycle 43 (up to 1083 days)

Population: Tumor biomarker analysis set included all treated participants who had at least one screening biomarker assessment, and had received at least one dose of any study drug. Here, "N" signifies number of participants who were evaluable for this outcome measure.

PD-L1- tumor proportion score was defined as the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. Participants with positive or negative scores were reported. PD-L1 negative: if tumor proportion score was less than 1%; PD-L1 positive: if the tumor proportion score greater than or equal to 1%.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=44 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Tumor Proportion Score Positive Score	9 Participants
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Tumor Proportion Score Negative Score	34 Participants
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Tumor Proportion Score Missing	1 Participants

SECONDARY outcome

Timeframe: Baseline up to Cycle 64 (up to 1344 days)

Population: PDL1 analyses didn't find any statistically significant associations between PDL1 status and response, hence data for this outcome measure (a sub-analyses on PDL1 positive participants) was not further collected and analyzed.

Vascular Endothelial Growth Factor (VEGF) promotes cancer progression by inducing angiogenesis via VEGF receptors, signals directly through receptors VEGFR-1 and VEGFR-2. Change in biomarkers related to VEGFR signal transduction pathways after axitinib treatment was assessed. Plasma VEGF concentration evaluations were performed using samples from peripheral blood plasma, bone marrow aspirate, bone marrow (Core) biopsy and bone marrow clot. The VEGFR, axitinib and mechanistic target of rapamycin inhibitor everolimus are used individually in subsequent lines of therapy for advanced clear cell renal cell carcinoma (ccRCC).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycle 2 Pre-dose, Post end of treatment or Withdrawal whichever came first (maximum of 1344 days)

Population: Tumor biomarker analysis set included all treated participants who had at least one screening biomarker assessment, and had received at least one dose of any study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows.

Vascular endothelial growth factor (VEGF) promotes cancer progression by inducing angiogenesis via VEGF receptors, signals directly through receptors VEGFR-1 and VEGFR-2. Change in biomarkers related to VEGFR signal transduction pathways after axitinib treatment was assessed. Mononuclear (MNC) cell VEGF receptor expression and phosphorylation was assessed by in situ western blot analysis. VEGFR-1 and VEGFR-2 evaluations were performed using samples from peripheral blood plasma, bone marrow aspirate, bone marrow (Core) biopsy and bone marrow clot. The VEGFR, axitinib and mechanistic target of rapamycin inhibitor everolimus are used individually in subsequent lines of therapy for advanced clear cell renal cell carcinoma (ccRCC).

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=51 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Concentration of Vascular Endothelial Growth Factor A (VEGF-A) in Serum Baseline	315.2 picogram per millilitre (pg/mL) Standard Deviation 286.6
Concentration of Vascular Endothelial Growth Factor A (VEGF-A) in Serum Cycle 2 Day 1	432.1 picogram per millilitre (pg/mL) Standard Deviation 315.0
Concentration of Vascular Endothelial Growth Factor A (VEGF-A) in Serum End of treatment	383.6 picogram per millilitre (pg/mL) Standard Deviation 360.4

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycle 2 Pre-dose, Post end of treatment or Withdrawal whichever came first (maximum of 1344 days)

Population: Tumor biomarker analysis set included all treated participants who had at least one screening biomarker assessment, and had received at least one dose of any study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=51 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Concentration of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in Serum Baseline	4.11 nanogram per milliliter (ng/mL) Standard Deviation 1.27
Concentration of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in Serum Cycle 2 Day 1	3.07 nanogram per milliliter (ng/mL) Standard Deviation 0.93
Concentration of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in Serum End of treatment	3.69 nanogram per milliliter (ng/mL) Standard Deviation 1.41

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycle 2 Pre-dose, Post end of treatment or Withdrawal whichever came first (maximum of 1344 days)

Population: Tumor biomarker analysis set included all treated participants who had at least one screening biomarker assessment, and had received at least one dose of any study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows.

Outcome measures

Outcome measures
Measure	Axitinib 5 mg + Pembrolizumab 2 mg: Dose Finding Phase n=51 Participants Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days).
Concentration of Interleukin 8 (IL-8) in Serum Baseline	NA mmol/L Standard Deviation NA Data could not be estimated as concentration of IL-8 was less than lower limit of quantification.
Concentration of Interleukin 8 (IL-8) in Serum Cycle 2 Day 1	NA mmol/L Standard Deviation NA Data could not be estimated as concentration of IL-8 was less than lower limit of quantification.
Concentration of Interleukin 8 (IL-8) in Serum End of treatment	NA mmol/L Standard Deviation NA Data could not be estimated as concentration of IL-8 was less than lower limit of quantification.

Adverse Events

Axitinib 5 mg + Pembrolizumab (MK-3475) 2 mg

Serious events: 29 serious events

Other events: 52 other events

Deaths: 14 deaths

Serious adverse events

Serious adverse events
Measure	Axitinib 5 mg + Pembrolizumab (MK-3475) 2 mg n=52 participants at risk Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days). Participants received axitinib up to a maximum of 64 cycles and pembrolizumab up to 56 cycles in dose expansion phase (each cycle of 21 days) until documented disease progression or unacceptable toxicity or study discontinuation criteria were met.
Cardiac disorders Atrial fibrillation	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Cardiac disorders Atrial flutter	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Cardiac disorders Bradycardia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Cardiac disorders Tachycardia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Endocrine disorders Adrenal insufficiency	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Eye disorders Periorbital oedema	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Abdominal pain	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Autoimmune colitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Colitis	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Diarrhoea	11.5% 6/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Nausea	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Small intestinal obstruction	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Vomiting	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Chills	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Fatigue	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Non-cardiac chest pain	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Pyrexia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Hepatobiliary disorders Cholecystitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Hepatobiliary disorders Cholecystitis acute	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Hepatobiliary disorders Drug-induced liver injury	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Hepatobiliary disorders Hepatitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Hepatobiliary disorders Hepatotoxicity	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Device related infection	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Perineal abscess	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Wound infection	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Alanine aminotransferase increased	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Aspartate aminotransferase increased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Diabetes mellitus	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Arthritis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Muscular weakness	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Cerebrovascular accident	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Presyncope	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Syncope	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Transient ischaemic attack	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Renal and urinary disorders Acute kidney injury	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Wheezing	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Vascular disorders Embolism	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Vascular disorders Hypotension	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Soft tissue mass	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Pyelonephritis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Hypersensitivity pneumonitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Cardiac disorders Supraventricular tachycardia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.

Other adverse events

Other adverse events
Measure	Axitinib 5 mg + Pembrolizumab (MK-3475) 2 mg n=52 participants at risk Participants with no prior systemic treatment for advance cancer, received axitinib 5 mg twice daily orally in combination with pembrolizumab (MK-3475) 2 mg/kg of body weight intravenous infusion every 3 weeks up to a maximum of 6 months in dose finding phase (each cycle of 21 days). Participants received axitinib up to a maximum of 64 cycles and pembrolizumab up to 56 cycles in dose expansion phase (each cycle of 21 days) until documented disease progression or unacceptable toxicity or study discontinuation criteria were met.
Blood and lymphatic system disorders Anaemia	21.2% 11/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Blood and lymphatic system disorders Polycythaemia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Blood and lymphatic system disorders Thrombocytopenia	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Cardiac disorders Bradycardia	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Cardiac disorders Palpitations	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Cardiac disorders Sinus bradycardia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Cardiac disorders Sinus tachycardia	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Cardiac disorders Tachycardia	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Ear and labyrinth disorders Ear discomfort	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Ear and labyrinth disorders Ear pain	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Ear and labyrinth disorders Excessive cerumen production	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Ear and labyrinth disorders Vertigo	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Endocrine disorders Hyperthyroidism	13.5% 7/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Endocrine disorders Hypothyroidism	44.2% 23/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Endocrine disorders Thyroiditis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Eye disorders Dry eye	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Eye disorders Erythema of eyelid	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Eye disorders Eye pain	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Eye disorders Eyelid oedema	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Eye disorders Periorbital oedema	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Eye disorders Vision blurred	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Eye disorders Visual impairment	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Abdominal discomfort	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Abdominal distension	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Abdominal pain	26.9% 14/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Abdominal pain lower	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Abdominal pain upper	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Aerophagia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Buccal mucosal roughening	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Colitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Constipation	36.5% 19/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Dental caries	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Diarrhoea	84.6% 44/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Dry mouth	21.2% 11/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Dyspepsia	19.2% 10/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Dysphagia	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Faeces discoloured	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Flatulence	11.5% 6/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Gastric ulcer	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Gastrointestinal disorder	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Gastrointestinal sounds abnormal	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Gastrooesophageal reflux disease	9.6% 5/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Gingival disorder	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Gingival pain	9.6% 5/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Glossodynia	9.6% 5/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Haemorrhoidal haemorrhage	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Haemorrhoids	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Hiatus hernia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Mouth haemorrhage	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Nausea	44.2% 23/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Odynophagia	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Oedema mouth	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Oral discomfort	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Oral disorder	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Oral pain	25.0% 13/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Plicated tongue	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Proctalgia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Rectal haemorrhage	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Stomatitis	15.4% 8/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Tongue discomfort	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Tongue disorder	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Tongue erythema	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Tongue geographic	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Tongue oedema	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Toothache	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Vomiting	28.8% 15/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Asthenia	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Catheter site erythema	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Catheter site haematoma	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Catheter site oedema	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Chest pain	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Chest discomfort	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Chills	13.5% 7/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Early satiety	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Face oedema	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Facial pain	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Fatigue	80.8% 42/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Gait disturbance	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Hernia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Influenza like illness	9.6% 5/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Localised oedema	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Mucosal inflammation	9.6% 5/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Non-cardiac chest pain	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Oedema	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Oedema peripheral	21.2% 11/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Pain	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Peripheral swelling	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Pyrexia	11.5% 6/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Hepatobiliary disorders Cholecystitis acute	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Hepatobiliary disorders Hepatitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Immune system disorders Contrast media allergy	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Immune system disorders Seasonal allergy	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Abscess jaw	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Bronchitis	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Candida infection	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Catheter site pustule	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Cellulitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Chronic sinusitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Conjunctivitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Fungal skin infection	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Gastroenteritis	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Gingivitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Herpes zoster	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Hordeolum	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Influenza	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Laryngitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Lip infection	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Localised infection	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Lower respiratory tract infection	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Oral candidiasis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Oropharyngitis fungal	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Osteomyelitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Parvovirus infection	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Pneumonia	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Rhinitis	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Sinusitis bacterial	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Skin candida	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Tooth infection	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Upper respiratory tract infection	19.2% 10/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Urinary tract infection	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Vulvovaginal mycotic infection	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Injury, poisoning and procedural complications Arthropod bite	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Injury, poisoning and procedural complications Contusion	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Injury, poisoning and procedural complications Fall	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Injury, poisoning and procedural complications Ligament sprain	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Injury, poisoning and procedural complications Rib fracture	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Injury, poisoning and procedural complications Tooth fracture	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Injury, poisoning and procedural complications Venous injury	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Activated partial thromboplastin time abnormal	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Activated partial thromboplastin time prolonged	9.6% 5/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Alanine aminotransferase increased	40.4% 21/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Aspartate aminotransferase increased	34.6% 18/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Bacterial test positive	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood alkaline phosphatase	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood alkaline phosphatase increased	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood bilirubin increased	11.5% 6/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood cholesterol increased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood creatine phosphokinase increased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood creatinine increased	30.8% 16/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood phosphorus increased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood pressure increased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood thyroid stimulating hormone decreased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood thyroid stimulating hormone increased	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood uric acid increased	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Cortisol decreased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Ejection fraction decreased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Electrocardiogram QT prolonged	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Gamma-glutamyltransferase increased	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Haemoglobin increased	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations International normalised ratio increased	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Liver function test increased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Lymphocyte count decreased	15.4% 8/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Neutrophil count decreased	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Neutrophil count increased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Platelet count decreased	15.4% 8/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Transaminases increased	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Weight decreased	34.6% 18/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Weight increased	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations White blood cell count decreased	9.6% 5/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations White blood cell count increased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Decreased appetite	44.2% 23/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Dehydration	13.5% 7/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Gout	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hypercalcaemia	9.6% 5/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hyperglycaemia	23.1% 12/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hyperkalaemia	13.5% 7/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hypermagnesaemia	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hypernatraemia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hyperuricaemia	21.2% 11/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hypoalbuminaemia	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hypocalcaemia	9.6% 5/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hypoglycaemia	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hypokalaemia	13.5% 7/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hypomagnesaemia	15.4% 8/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hyponatraemia	23.1% 12/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Metabolism and nutrition disorders Hypophosphataemia	17.3% 9/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Arthralgia	34.6% 18/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Arthritis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Arthropathy	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Back pain	19.2% 10/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Bone pain	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Costochondritis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Flank pain	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Joint stiffness	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Muscle spasms	9.6% 5/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Muscular weakness	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Myalgia	15.4% 8/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Myositis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Neck pain	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Pain in extremity	13.5% 7/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Pain in jaw	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Polycythaemia vera	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Amnesia	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Balance disorder	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Carotid artery stenosis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Cerebral infarction	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Cognitive disorder	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Disturbance in attention	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Dizziness	30.8% 16/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Dysgeusia	21.2% 11/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Head discomfort	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Headache	32.7% 17/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Hyperaesthesia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Loss of proprioception	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Memory impairment	9.6% 5/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Neuralgia	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Neuropathy peripheral	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Paraesthesia	17.3% 9/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Presyncope	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Syncope	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Tremor	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Psychiatric disorders Agitation	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Psychiatric disorders Anxiety	13.5% 7/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Psychiatric disorders Confusional state	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Psychiatric disorders Depression	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Psychiatric disorders Insomnia	17.3% 9/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Psychiatric disorders Libido decreased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Renal and urinary disorders Chronic kidney disease	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Renal and urinary disorders Dysuria	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Renal and urinary disorders Haematuria	15.4% 8/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Renal and urinary disorders Micturition urgency	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Renal and urinary disorders Pollakiuria	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Renal and urinary disorders Proteinuria	34.6% 18/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Reproductive system and breast disorders Cystocele	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Reproductive system and breast disorders Genital rash	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Reproductive system and breast disorders Penile pain	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Reproductive system and breast disorders Rectocele	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Reproductive system and breast disorders Uterine prolapse	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Reproductive system and breast disorders Vulval disorder	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Reproductive system and breast disorders Vulvovaginal dryness	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Asthma	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Cough	48.1% 25/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Dysphonia	48.1% 25/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea	28.8% 15/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	15.4% 8/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Epistaxis	11.5% 6/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Hiccups	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Nasal congestion	26.9% 14/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Oropharyngeal cobble stone mucosa	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	23.1% 12/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Pharyngeal disorder	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Pleurisy	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Productive cough	15.4% 8/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Sinus congestion	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Throat irritation	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Wheezing	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Acne	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Alopecia	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Blister	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Dermal cyst	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Dermatitis	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Dermatitis acneiform	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Dry skin	23.1% 12/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Erythema	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Exfoliative rash	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Hyperkeratosis	7.7% 4/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Nail ridging	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Night sweats	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Onychoclasis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Pain of skin	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	36.5% 19/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Papule	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Pruritus	23.1% 12/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Pruritus generalised	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Psoriasis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Rash	26.9% 14/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Rash maculo-papular	19.2% 10/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Rash papular	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Rash pruritic	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Skin discolouration	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Skin disorder	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Skin exfoliation	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Skin fissures	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Skin hypopigmentation	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Skin lesion	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Skin reaction	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Skin ulcer	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Swelling face	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Telangiectasia	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Surgical and medical procedures Central venous catheterisation	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Vascular disorders Embolism	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Vascular disorders Flushing	5.8% 3/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Vascular disorders Hot flush	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Vascular disorders Hypertension	53.8% 28/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Vascular disorders Hypotension	15.4% 8/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Vascular disorders Labile blood pressure	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Vascular disorders Thrombophlebitis superficial	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Vascular disorders Varicose vein	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Ear and labyrinth disorders Tinnitus	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Ear and labyrinth disorders Tympanic membrane perforation	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Eye disorders Blepharitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Gastrointestinal disorders Proctitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Ill-defined disorder	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Prolapse	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
General disorders Swelling	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Cystitis	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Ear infection	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Fungal infection	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Nasopharyngitis	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Infections and infestations Tooth abscess	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Injury, poisoning and procedural complications Skin abrasion	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Injury, poisoning and procedural complications Skin laceration	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Activated partial thromboplastin time	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Bilirubin urine	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood creatine increased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood phosphorus decreased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood potassium decreased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Blood uric acid abnormal	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Investigations Pancreatic enzymes decreased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Nervous system disorders Taste disorder	3.8% 2/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Renal and urinary disorders Acute kidney injury	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Reproductive system and breast disorders Erectile dysfunction	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Sinus disorder	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Respiratory, thoracic and mediastinal disorders Sneezing	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Dermatitis contact	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Surgical and medical procedures Central venous catheter removal	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	1.9% 1/52 • Baseline up to 28 days after last dose of study drug (approximately up to 1552 days) The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. All treatment emergent AEs and non SAEs were collected and reported.

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